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[ "17448820", "1503326", "9231947", "16306456", "12100367", "15045129" ]

[ "The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison.", "A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study.", "A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke.", "Prophylaxis of thrombotic and embolic events in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the PROTECT Trial.", "Enoxaparin vs heparin for prevention of deep-vein thrombosis in acute ischaemic stroke: a randomized, double-blind study.", "Treatment with anticoagulants in cerebral events (TRACE)." ]

[ "Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke.\n 1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805.\n In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015).\n Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.", "To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke.\n Double-blind randomized trial.\n Seven Canadian university-affiliated hospitals.\n Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis.\n Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner.\n Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically.\n Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups.\n Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.", "A multicentre, double-blind, randomized study was performed in 179 patients with acute ischaemic stroke resulting in limb paresis. The purpose was to compare the safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT). Prophylaxis started within 72 hours of the onset of stroke and continued for at least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg scanning which, if found positive, was followed by venography. A first computed tomography scan of the brain was performed at screening to rule out cerebral haemorrhage and a second at cessation of treatment to detect any haemorrhagic transformations. At the 2-3-months' follow-up period the patients were examined for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary embolism was diagnosed in one patient in each group. Major conversion to a symptomatic haemorrhagic brain infarct was found in one patient in each group. Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of patients treated with heparin (p = 0.135, NS). Deaths were mainly related to pulmonary infection and cerebral oedema, thus considered to be due directly to the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily is both safe and as effective as 5000 IU of heparin sodium twice daily given for DVT prophylaxis in patients with acute ischaemic stroke of recent onset.", "Patients with stroke are at substantial risk of thromboembolic complications and therefore require antithrombotic prophylaxis. To show the noninferiority of the low-molecular-weight heparin certoparin to unfractionated heparin (UFH) for the prevention of thromboembolic complications, we performed a randomized, double-blind, active-controlled multicenter trial in patients with acute ischemic stroke.\n Overall, 545 patients were randomized within 24 hours of stroke onset to treatment with certoparin (3000 U anti-Xa OD; n=272) or UFH (5000 U TID; n=273) for 12 to 16 days. Patients with paresis of a leg and an National Institutes of Health Stroke Scale score of 4 to 30 points were included. The primary end point was a composite outcome of proximal deep vein thrombosis, pulmonary embolism, or death related to venous thromboembolism during treatment. Computed tomography was performed at trial entry, after 7 days, and when clinical deterioration occurred.\n The per-protocol analysis revealed 17 (7.0%) primary events in the certoparin group compared with 24 (9.7%) in the UFH group, thereby demonstrating noninferiority (P=0.0011), confirmed by intention-to-treat analysis (6.6% versus 8.8%; P=0.008). Major bleeding occurred during treatment in 3 patients allocated to certoparin (1.1%) and 5 patients allocated to UFH (1.8%).\n Certoparin (3000 U anti-Xa OD) is at least as effective and safe as UFH (TID) for the prevention of thromboembolic complications in patients with acute ischemic stroke.", "To compare the efficacy, safety, and overall risk-benefit profile of enoxaparin and unfractionated heparin (UFH) prophylaxis of venous thromboembolic complications in patients with acute ischaemic stroke.\n Patients with ischaemic stroke resulting in lower-limb paralysis lasting for at least 24 h and necessitating bedrest, were randomized within 48 h of the onset of stroke, and treated with enoxaparin (40 mg subcutaneously once daily) or UFH (5000 IU subcutaneously thrice daily) for 10 +/- 2 days. Main outcome measures were deep-vein thrombosis, pulmonary embolism (PE), death from any cause, intracranial haemorrhage including haemorrhagic infarction, or any other major bleeding.\n Outcome events occurred within 3 months of stroke in 40/106 patients treated with enoxaparin (37.7%) and 52/106 patients treated with UFH (49.1%, P=0.127). Fewer patients treated with enoxaparin (14, 13.2%) than with UFH (20, 18.9%) had evidence of haemorrhagic transformation of ischaemic stroke.\n Enoxaparin administered subcutaneously once daily was as safe and effective as subcutaneous UFH given thrice daily in the prevention of thromboembolic events in patients with lower limb paralysis caused by acute ischaemic stroke.", "90 patients with acute stroke and a concomitant cardiac embolism source or a symptomatic high-grade stenosis of an extra-or intracranial vessel received in a mulitcenter, randomized, controlled study either Enoxaparin 1 mg/kg BW s.c. b.i.d. or i.v. heparin aPTT-adjusted daily for 8 +/- 2 days as secondary prophylaxis. There were no significant differences between the two groups regarding cerebral and systemic embolic events, bleeding complications, length of hospital stay, number of diagnostic and therapeutic measures and outcome after three months. This suggests that Enoxaparin, which is easier to administer and monitor, is a safe drug in patients with acute cerebral events." ]

[ "4603278", "2290163", "9855212", "3735283", "11678298", "3890159", "6416401", "7002481", "9688036", "9804720", "11408900", "2712613", "1985618", "11552189", "10774861", "53845", "8348279", "8934482", "6742895" ]

[ "Periarthritis of the shoulder: a controlled trial of physiotherapy.", "A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.", "Treatment of \"frozen shoulder\" with distension and glucorticoid compared with glucorticoid alone. A randomised controlled trial.", "Rotator cuff tendinitis: comparison of subacromial injection of a long acting corticosteroid versus oral indomethacin therapy.", "Comparison of the efficacy of local corticosteroid injection and physical therapy for the treatment of adhesive capsulitis.", "A placebo-controlled trial of steroid injections in the treatment of supraspinatus tendonitis.", "Comparison of injection techniques for shoulder pain: results of a double blind, randomised study.", "Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.", "Intra-articular triamcinolone acetonide injection in patients with capsulitis of the shoulder: a comparative study of two dose regimens.", "Effectiveness of corticosteroid injections versus physiotherapy for treatment of painful stiff shoulder in primary care: randomised trial.", "Clinical evaluation of sodium hyaluronate for the treatment of patients with rotator cuff tear.", "Injections and physiotherapy for the painful stiff shoulder.", "Corticosteroid injections in adhesive capsulitis: investigation of their value and site.", "Manipulation under anesthesia for frozen shoulder with and without steroid injection.", "Local anaesthetic injection with and without corticosteroids for subacromial impingement syndrome.", "Ernest Fletcher Lecture. The painful shoulder.", "A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis.", "Efficacy of injections of corticosteroids for subacromial impingement syndrome.", "Frozen shoulder: prospective clinical study with an evaluation of three treatment regimens." ]

[ "nan", "A prospective double blind placebo controlled study was carried out to compare the effects of subacromial injection of triamcinolone and oral diclofenac in patients with rotator cuff tendinitis over a 4-week period. Both forms of treatment were superior to placebo in reducing pain, improving active abduction and reducing functional limitation. Triamcinolone showed the greatest effect in these respects, and was significantly superior to diclofenac when patients showing improvements in all 3 variables together (responders) were considered.", "This study is a comparison of treatments of idiopathic \"Frozen Shoulder\" (adhesive capsulitis), distension combined with steroid is compared with steroid alone. Evaluation was based on pain scales, analgesic usage, and range of motion outcome scales. Out of one-hundred twenty patients (age, mean 51, range 21-70) that were referred under the diagnosis FS, twenty-six fulfilled the criteria for inclusion in the study, but four patients did not want to participate in the trial, giving a total of 22 patients (age, mean 53, range 40-65) in the study. Patients were randomised by the envelope method. Two patients dropped-out, one in each treatment group thus leaving the study with 20 patients for the final statistical analysis. Eight were treated with steroid alone and 12 with distension combined with steroid. Patients received one treatment per week for a six weeks period with a follow-up at 12 weeks. They were evaluated by pain VAS on function and at rest within the study period, the different ranges of motion (ROM) were measured at inclusion time and subsequent afterwards at 3, 6, and 12 weeks. The VAS outcomes showed no difference between the treatments (VAS-function p=0,1; VAS-rest p=0.1), while in the distension group ROM showed significant improvement in all directions except extension (external p=0.0007, flexion p=0.03, extension p=0,01). The analgesic usage was significantly lower in the group treated with distension at the end of the study (p=0.008). A blinded clinical assessment of ROM also showed significant improvement (p=0.002). It is concluded that distension with steroid can seem to help in management of \"Frozen Shoulder\". Other studies seems to support the conclusion.", "Using a prospective, double blind, double dummy protocol, we compared the efficacy of subacromial injection of 40 mg of triamcinalone acetonide versus oral indomethacin, 100 mg/day, in 40 patients with acute rotator cuff tendinitis. Repeat injection and refill of medication was given after 3 weeks, if necessary. At 6 weeks, there was no significant difference between the 2 groups with respect to the percentage of patients who improved (60 vs 66%) or the magnitude of the change of pain and motion variables. This study suggests that there is essentially no difference in the short term efficacy of oral nonsteroidal therapy compared to local corticosteroid injection(s) in the treatment of rotator cuff tendinitis.", "Adhesive capsulitis is a common musculoskeletal disorder mainly affecting middle aged adults. It is associated with generalized pain and tenderness in the shoulder joint with severe loss of active and passive ranges of motion in all planes. The aim of this study was to compare the efficacy of local steroid injection and physical therapy measures for treating this disorder. Ten male and 10 female patients were enrolled in the study. The patients were divided randomly into two groups and treated with either 40 mg methylprednisolone acetate injection with local anesthetic (group A) or physical therapy measures plus nonsteroidal anti-inflammatory drugs (group B). The mean ages of the patients were 55.6+/-12.2 years in group A and 56.4+/-7.1 years in group B. Clinical assessment was performed on initial visit and at the 2nd and 12th weeks. Active and passive range of motion was recorded and the visual analogue scale was used to evaluate pain intensity. At initial visit, these data in both groups of patients were not statistically different. Although both treatment regimens resulted in significant improvement in range of motion, the differences between mean external rotation at the 2nd and 12th weeks were not statistically significant in either group. The improvement in range of motion at the end of the study was similar in both groups (P>0.05). All patients reported improvement during the study. The differences between mean VAS scores at the 2nd and 12th weeks were statistically significant in both groups. In conclusion, local steroid injection therapy was found to be as effective as physical therapy for the treatment of adhesive capsulitis.", "In this report of a double-blind placebo-controlled trial of steroid injections for supraspinatus tendonitis, there was no statistical difference in the improvement in pain score between the two groups at 2 and 8 weeks of follow-up or in analgesic consumption. This trial casts further doubt on the efficacy of such treatment in soft tissue lesions around the shoulder.", "Seventy seven patients with soft tissue shoulder lesions including adhesive capsulitis and disorders of the rotator cuff and acromioclavicular joint were admitted to a trial comparing two different methods of corticosteroid injection with local anaesthetic in a randomly allocated double blind study. The method of anatomical injection after diagnosis by the technique of selective tissue tension gave 60% success compared with the method using tender or trigger point localisation, giving 20% success (p less than 0.001).", "In a single-blind trial, five treatments for painful stiff shoulder were compared for a 4-week assessment period in 60 patients. The treatments were acupuncture, steroid injection with placebo and with active tolmetin sodium, physiotherapy in the form of ultrasound and 'placebo' physiotherapy with placebo tolmetin sodium. Objective assessment was gained by use of goniometer readings to monitor shoulder abduction. Pain was measured by visual analogue scales and by a 4-point scale. Comparative assessment was also recorded and at the end of the study a success or failure was recorded for each patient's treatment. With very few exceptions all patients improved markedly, both in terms of the subjective and objective parameters. No differences between the treatments were detected. The incidence and severity of side-effects was low. It is suggested that the results show that the painful stiff shoulder may be a self-limiting condition and that any beneficial effect was really due to natural recovery. This is an important consideration because patients do not always receive immediate attention when referred to an out-patient department and the use of physiotherapy and acupuncture in such cases, perhaps, should be critically examined.", "Although corticosteroid injections have been reported to be effective in capsulitis of the shoulder, the optimal dose has not been established. The purpose of this study was to compare relief of symptoms following a lower dose with that following a higher dose of triamcinolone acetonide given intra-articularly.\n Thirty-two patients were given low dose suspension; 25 patients were given high dose suspension.\n Randomized, double-blind clinical trial. Each patient was given a course of three injections. Pain, sleep disturbance, functional impairment and passive range of motion (ROM) were assessed at intake and at one, three and six weeks after the initial injection. Data were analysed by independent sample t-tests and nonparametric Mann-Whitney U-tests.\n The group which received the 40 mg dose showed significantly greater improvement than the group receiving the 10 mg dose.\n The study shows that in the treatment of frozen shoulder greater symptom relief is obtained with a dose of 40 mg triamcinolone acetonide intra-articularly than with a dose of 10 mg. The effect on pain and sleep disturbance was more marked than on ROM. Intra-articular injections with triamcinolone acetonide appear to be an effective method to obtain symptom relief for patients with painful capsulitis of the shoulder.", "To compare the effectiveness of corticosteroid injections with physiotherapy for the treatment of painful stiff shoulder.\n Randomised trial.\n 40 general practices.\n 109 patients consulting general practitioners for shoulder pain were enrolled in the trial.\n Patients were randomly allocated to 6 weeks of treatment either with corticosteroid injections (53) or physiotherapy (56).\n Outcome assessments were carried out 3, 7, 13, 26, and 52 weeks after randomisation; some of the assessments were done by an observer blind to treatment allocation. Primary outcome measures were the success of treatment as measured by scores on scales measuring improvement in the main complaint and pain, and improvement in scores on a scale measuring shoulder disability.\n At 7 weeks 40 (77%) out of 52 patients treated with injections were considered to be treatment successes compared with 26 (46%) out of 56 treated with physiotherapy (difference between groups 31%, 95% confidence interval 14% to 48%). The difference in improvement favoured those treated with corticosteroids in nearly all outcome measures; these differences were statistically significant. At 26 and 52 weeks differences between the groups were comparatively small. Adverse reactions were generally mild. However, among women receiving treatment with corticosteroids adverse reactions were more troublesome: facial flushing was reported by 9 women and irregular menstrual bleeding by 6, 2 of whom were postmenopausal.\n The beneficial effects of corticosteroid injections administered by general practitioners for treatment of painful stiff shoulder are superior to those of physiotherapy. The differences between the intervention groups were mainly the result of the comparatively faster relief of symptoms that occurred in patients treated with injections. Adverse reactions were generally mild but doctors should be aware of the potential side effects of injections of triamcinolone, particularly in women.", "A randomized study of two types of conservative treatment of 78 shoulders in 78 patients with rotator cuff tears was performed. Twenty-five milligrams of sodium hyaluronate (SH) was injected into shoulders in one group (SH group) and 2 mg of dexamethasone was injected in the other group (steroid group). Injection of each drug was planned for once per week for 5 consecutive weeks. In the SH group, University of California at Los Angeles score before treatment was 13.6 +/- 2.6 points in 16 patients who did not require surgery (satisfied patients) and 12.8 +/- 3.5 points in 22 patients who required surgery (unsatisfied patients) (not statistically significant). In the steroid group, University of California at Los Angeles score before treatment was 11.9 +/- 3.6 points for 15 satisfied patients and 12.6 +/- 3.9 points for 25 unsatisfied patients (again, not statistically significant). In the SH group, the score at 4 weeks after treatment for satisfied patients increased to 27.6 +/- 3.1 points, whereas that for unsatisfied patients was 14.9 +/- 1.2 points (P <.0001). Similarly, in the steroid group, the score at 4 weeks after the treatment for satisfied patients increased to 26.5 +/- 2.0 points, whereas that for unsatisfied patients was 15.0 +/- 4.0 points (P <.0001). At 24 weeks after treatment, the score for satisfied patients was 26.2 +/- 3.1 points in the SH group and 25.3 +/- 2.5 points in the steroid group. The effective rate of the SH group was 39.5% and that of the steroid group was 35%. Therapeutic efficacy in the SH group was equivalent to that in the steroid group. In both groups, the rate of patients who engaged in manual labor was significantly higher in the group of unsatisfied patients than in that of satisfied patients. No adverse reaction to either treatment was observed. These results suggest that SH is an effective conservative treatment for patients with rotator cuff tears.", "Cost effective treatment is needed for common self limiting rheumatological conditions. Periarthritis of the shoulder is an example. There is no consensus for one type of treatment, though local steroids or physiotherapy are conventionally used. Their cost and efficacy were compared in a prospective randomised observer-blind trial--in essence a medical audit of the treatment of a common rheumatological problem. Sixty two consecutive patients presenting with a painful stiff shoulder were studied. Patients with coexistent diseases like cervical spondylosis or a stroke were excluded. They were randomly allocated to receive local steroids, six weeks' physiotherapy, or both. The three groups were of similar age, sex, and disease severity. Assessments of pain and shoulder movement were made initially, at six weeks, and at six months by a 'blinded' observer. Physiotherapy was given by one therapist and injections by one physician. All three groups showed significant improvements by six weeks, with further improvement at six months. Improvements were identical in all three groups. No treatment gave complications. The costs of treatment varied: an injection of triamcinolone cost 2.10 pounds; a six week course of physiotherapy cost 48.50 pounds; combination treatment cost 50.60 pounds. Patients expect treatment for a painful stiff shoulder. The results show that local steroid injections are as effective as physiotherapy alone or a combination. They provide rapid treatment and are less expensive. In the uncomplicated case a local steroid injection is the most cost effective treatment.", "Forty-eight patients with frozen shoulder for less than six months were assigned at random to receive three shoulder injections into the subacromial bursa or glenohumeral joint at weekly intervals. The treatment groups were (1) intra-articular methylprednisolone and lidocaine, (2) intrabursal methylprednisolone and lidocaine, (3) intra-articular lidocaine, (4) intrabursal lidocaine. The same physical therapy program was carried out for all patients. Assessments of pain and range of motion were performed by a physical therapist who was uninformed about the nature of the injection therapy. There was no significant difference in outcome between intrabursal injection and intra-articular injection. Injection of steroid with lidocaine had no advantage over lidocaine alone in restoring shoulder motion, but partial, transient pain relief occurred in two thirds of the steroid-treated patients.", "To study the effect of manipulating a shoulder with adhesive capsulitis (frozen shoulder) under anesthesia with and without corticosteroid injection.\n Randomized trial.\n Hospital.\n Twenty-four patients referred for manipulation of a frozen shoulder.\n The patients were randomized into 2 groups. One group received an injection of corticosteroid and manipulation; the other was only administered manipulation during anesthesia.\n The degree of shoulder mobility and pain before and after the manipulation.\n Manipulation under anesthesia increased the mobility of the affected shoulder. Injection with lidocaine and betamethason did not enhance the effect of the manipulation.\n Manipulation under anesthesia without intraarticular corticosteroids is recommended as the therapy for frozen shoulder.", "Fifty patients with impingement syndrome refractory to long-term conservative treatment were randomized to three treatment groups. All patients received an injection of 10 ml 0.5% bupivacaine, in group 1 without corticosteroid, in group 2 with crystalline corticosteroid and in group 3 with lipoid corticosteroid. Treatment in group 1 had to be stopped because of inefficacy. In groups 2 and 3 favorable results were achieved in 19 out of 40 patients.", "nan", "Fifty-five patients with shoulder pain due to rotator cuff tendinitis of less than 12 weeks' duration were randomized to receive either 40 mg methylprednisolone and lignocaine or lignocaine alone. No statistically significant difference could be discerned between the two groups during 12 weeks of follow-up.", "A prospective, randomized, controlled, double-blind clinical study was performed to determine the short-term efficacy of subacromial injection of corticosteroids for the treatment of subacromial impingement syndrome. Forty patients were randomized to receive either six milliliters of 1 per cent lidocaine without epinephrine (the control group) or two milliliters containing forty milligrams of triamcinolone acetonide per milliliter with four milliliters of 1 per cent lidocaine without epinephrine (the corticosteroid group). The patients were re-examined serially until completion of the study. Nineteen patients, whose mean age was fifty-six years (range, thirty-two to eighty years), were randomized to the corticosteroid group, and twenty-one patients, whose mean age was fifty-seven years (range, thirty-two to eighty-one years), were randomized to the control group. The mean duration of symptoms before the injection was eight months for both groups. Eighteen patients in the corticosteroid group and nineteen patients in the control group had moderate or severe pain before the injection. At the most recent follow-up evaluation, at a mean of thirty-three weeks for the corticosteroid group and twenty-eight weeks for the control group, three patients in the corticosteroid group had moderate or severe pain, compared with fifteen patients in the control group. The mean active range of forward elevation and external rotation improved by 24 and 11 degrees, respectively, for the corticosteroid group and by 10 and 5 degrees, respectively, for the control group. We concluded that subacromial injection of corticosteroids is an effective short-term therapy for the treatment of symptomatic subacromial impingement syndrome. The use of such injections can substantially decrease pain and increase the range of motion of the shoulder.", "Forty-two patients with frozen shoulder were followed up closely for eight months. They were all taught pendular exercises and randomly allocated to one of four treatment groups: (a) intraarticular steroids, (b) mobilisations , (c) ice therapy, (d) no treatment. This study has shown that there is little long-term advantage in any of the treatment regimens but that steroid injections may benefit pain and range of movement in the early stages of the condition." ]

[ "10373132" ]

[ "Persistent nocturnal cough: randomised controlled trial of high dose inhaled corticosteroid." ]

[ "To investigate the effect of a short course of inhaled corticosteroid in the treatment of isolated and persistent nocturnal cough in children.\n Randomised double blind placebo controlled study.\n Subjects' homes in east London, England.\n Consecutively referred children, 1-10 years old, with persistent nocturnal cough.\n Placebo or fluticasone propionate 1 mg twice daily for three nights and 500 microg twice daily for 11 nights. Videotaping of children at night: two nights' baseline, nights 3 and 4 after three days of inhaled corticosteroid, and nights 15 and 16.\n A fall in 75% of coughs from baseline.\n 50 subjects were recruited. The median number of coughs in the baseline period for the inhaled corticosteroid group and placebo group were 92 and 71, respectively (p = 0.43) and, on nights 15 and 16, 8 and 36, respectively (p < 0. 01). Compared to baseline, both groups of subjects improved significantly by nights 15 and 16 (p < 0.01; p < 0.01). Comparing the inhaled corticosteroid and placebo groups, coughs fell to a median of 22% and 57% of baseline totals on nights 3 and 4, respectively (p = 0.38), and 8% and 35% on nights 15 and 16, respectively (p = 0.02). 17 of 24 subjects on inhaled corticosteroid who completed the study and 8 of 23 on placebo improved by 75% after two weeks (p = 0.03).\n Children with persistent nocturnal cough improve in two weeks after referral on placebo. There is a modest benefit from a two week course of high dose inhaled corticosteroid." ]

[ "7888970", "1873454", "7873952", "9259219", "10617523", "14990522", "15596155", "9386883" ]

[ "Controlled evaluation of a general practice-based brief intervention for excessive drinking.", "A randomized trial of smoking cessation interventions in general practice in Italy.", "Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care.", "Group therapy for somatization disorders in general practice: effectiveness of a short cognitive-behavioural treatment model.", "Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care.", "Efficacy of cognitive-behavioural therapy by general practitioners for unexplained fatigue among employees: Randomised controlled trial.", "Psychosocial interventions for somatizing patients by the general practitioner: a randomized controlled trial.", "Reducing alcohol consumption. Comparing three brief methods in family practice." ]

[ "In a controlled evaluation of general practitioner (GP)-based brief intervention, 378 excessive drinkers identified opportunistically by screening in 40 group practices in metropolitan Sydney were assigned to groups receiving: (i) a five-session intervention by the GP (the Alcoholscreen Program); (ii) a single session of 5 minutes' advice by the GP plus a self-help manual (minimal intervention); (iii) an alcohol-related assessment but no intervention; (iv) neither intervention nor assessment. Among all patients allocated to receive it, the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up. A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample. There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems. Implications for further research into GP-based brief interventions are discussed.", "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.", "To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients.\n Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks.\n Primary care in Oxfordshire.\n 91 patients in primary care who had major depression.\n Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks.\n At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours.\n As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients.", "The objective of this study was to evaluate the effect of a short cognitive behavioural group therapy programme for somatization disorder in primary care. The treatment model was focused on patient education and stress relaxation. A controlled and prospective study design was used with repeated assessments of the patients' perception of their psychosocial problems, psychological distress and medication usage. The results were analysed up to 6 months after treatment and showed the treated patients to be moderately but significantly improved with respect to physical illness and somatic preoccupation, hypochondriasis, and medication usage. In a control group of untreated patients no such improvements were observed. In summary, the short group treatment programme used in this study may be beneficial for patients with somatization disorders. With some modifications it might be useful to practitioners in primary care for the management of psychosomatic disorders.", "To determine whether problem solving treatment combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care. To assess the effectiveness of problem solving treatment when given by practice nurses compared with general practitioners when both have been trained in the technique.\n Randomised controlled trial with four treatment groups.\n Primary care in Oxfordshire.\n Patients aged 18-65 years with major depression on the research diagnostic criteria-a score of 13 or more on the 17 item Hamilton rating scale for depression and a minimum duration of illness of four weeks.\n Problem solving treatment by research general practitioner or research practice nurse or antidepressant medication or a combination of problem solving treatment and antidepressant medication.\n Hamilton rating scale for depression, Beck depression inventory, clinical interview schedule (revised), and the modified social adjustment schedule assessed at 6, 12, and 52 weeks.\n Patients in all groups showed a clear improvement over 12 weeks. The combination of problem solving treatment and antidepressant medication was no more effective than either treatment alone. There was no difference in outcome irrespective of who delivered the problem solving treatment.\n Problem solving treatment is an effective treatment for depressive disorders in primary care. The treatment can be delivered by suitably trained practice nurses or general practitioners. The combination of this treatment with antidepressant medication is no more effective than either treatment alone.", "Fatigue is a common complaint that may lead to long-term sick leave and work disability.\n To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue among employees.\n A randomised controlled trial, using a pre-randomisation design in primary care, investigated 151 employees on sick leave with fatigue. Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner; those in the control group were offered no treatment. Main outcome measures (fatigue severity, self-reported absenteeism, registered absenteeism and clinical recovery) were assessed at 4 months, 8 months and 12 months.\n At baseline, 44% of the patients already met research criteria for chronic fatigue syndrome. There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point.\n Cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue did not prove to be an effective intervention. Since these doctors were unable to deliver this therapy effectively under ideal circumstances, it is unlikely that doctors in routine practice would be more successful in doing so.", "The objective of this study was to compare the effects of psychosocial interventions based on the modified reattribution model for somatizing patients in general practice (GP) with those of nonspecific psychosocial primary care (PPC) alone.\n Forty-two GPs were randomized, 23 into the intervention group (IG), who were trained in reattribution techniques, and 19 into the control group (CG). One hundred twenty-seven patients were included. Primary outcome measures were somatoform symptoms and quality of life.\n Multilevel modeling revealed a reduction of physical symptoms (P = .007), an improvement in physical functioning (P = .0172), and a reduction of depression (P = .0211) and anxiety (P = .0388) in the IG compared with the CG at the 3-month follow-up. However, results no longer remained significant after controlling for baseline and covariate variables besides a reduction of physical symptoms at 6-month follow-up (P = .029).\n Compared with nonspecific PPC, the effects of reattribution techniques were small and limited to physical symptoms.", "To compare the effects of three brief methods of reducing alcohol consumption among family practice patients.\n Patients randomly assigned to one of three interventions were assessed initially and at 3-, 6-, and 12-month follow-up appointments.\n Family practice clinic composed of 12 primary care physicians seeing approximately 6000 adults monthly in a small urban community, population 40,000.\n Through a screening questionnaire, 134 men and 131 women were identified as hazardous drinkers (five or more drinks at least once monthly) during an 11-month screening of 1420 patients. Of 265 patients approached, 180 agreed to participate and 159 (83 men and 76 women) actually participated in the study.\n Three interventions were studied: brief physician advice (5 minutes), two 30-minute sessions with a physician using cognitive behavioural strategies or two 30-minute sessions with a nurse practitioner using identical strategies.\n Quantity and frequency (QF) of drinking were used to assess reduction in hazardous drinking and problems related to drinking over 12 months of follow up.\n No statistical difference between groups was found. The QF of monthly drinking was reduced overall by 66% (among men) and 74% (among women) for those reporting at least one hazardous drinking day weekly at assessment (N = 96). Men reported drinking significantly more than women.\n These results indicated that offering brief, specific advice can motivate patients to reduce their alcohol intake. There was no difference in effect between brief advice from their own physician or brief intervention by a physician or a nurse." ]

[ "8267038", "8739461", "11270643", "9065133", "9262298", "9022487", "12632426", "9166175", "9219700", "11470043", "1595785", "12220757", "10649166" ]

[ "Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.", "A clinical trial for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss with lower dose heparin and aspirin.", "Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies: a comparative study of intravenous immunoglobulin versus prednisone plus low-dose aspirin.", "Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone.", "Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.", "Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)", "Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies.", "Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial.", "Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.", "Appropriate management of antiphospholipid-related pregnancy in women without lupus who have low titer autoantibodies.", "Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment.", "Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.", "A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group." ]

[ "We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome.\n Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished.\n Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth.\n The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.", "This study was conducted to determine if lower dose heparin (LD Heparin) combined with aspirin is as efficacious as higher dose heparin (HD Heparin) for the treatment of the antiphospholipid antibody syndrome in women seeking pregnancy. The method of the study was a prospective, single center trial including 50 patients who were consecutively assigned to treatment. Each patient had at least three consecutive, spontaneous pregnancy losses, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Data were compared using Fisher's exact test. Viable infants were delivered from 20/25 (80%) women treated with higher dose heparin vs. 19/25 (76%) of women treated with lower dose heparin. There were no significant differences between groups with respect to gestational age at the time of delivery (37.2 +/- 3.4 versus 37.7 +/- 1.6 weeks), maternal complications, or fetal complications. A lower dose of heparin plus aspirin was as effective as higher dose heparin for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss.", "To compare the use of intravenous immunoglobulins (IVIG) with prednisone plus low-dose aspirin (LDA) in treating pregnant women with a history of recurrent fetal loss having the antiphospholipid antibody (aPL), in terms of live-birth rate and maternal and perinatal morbidity.\n A prospective, two-centers trial study included 82 recurrent aborters with aPL syndrome. Twenty-nine were treated with prednisone and LDA in one center, 53 received IVIG in the other center. Maternal and fetal outcomes and pregnancy complications were compared between groups.\n Live-birth rates were equivalent between groups (78 vs 76%). Mean birth weight was higher in the IVIG group than in the prednisone plus LDA group. In the prednisone- plus LDA-treated patients, gestational hypertension and gestational diabetes were found significantly more often than in the IVIG-treated group (14 vs 5% and 14 vs 5%, respectively).\n In patients with aPL syndrome, IVIG treatment improved pregnancy outcome, with significantly lower pregnancy complication rates, when compared with prednisone plus LDA therapy.", "The purpose of this study was to compare the use of low-dose aspirin alone with heparin and low-dose aspirin in the treatment of the antiphospholipid antibody syndrome.\n A prospective, single-center trial included 50 patients who were alternately assigned to treatment. Each patient had at least three consecutive spontaneous pregnancy losses, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Data were compared by chi(2) analysis and Fisher's exact test.\n Viable infants were delivered of 11 of 25 (44%) women treated with aspirin and 20 of 25 (80%) women treated with heparin and aspirin (p < 0.05). There were no significant differences between the low-dose aspirin and the heparin plus low-dose aspirin groups with respect to gestational age at delivery (37.8 +/- 2.1 vs 37.2 +/- 3.4 weeks), number of cesarean sections (18% vs 20%), or complications.\n Heparin plus low-dose aspirin provides a significantly better pregnancy outcome than low-dose aspirin alone does for antiphospholipid antibody-associated recurrent pregnancy loss.", "Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.", "To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).\n Randomised controlled trial.\n Specialist clinic for recurrent miscarriages.\n 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.\n Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation.\n Rate of live births with the two treatments.\n There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%).\n Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.", "To compare the 2 most efficacious therapeutic regimens, intravenous immunoglobulin (IVIG) and anticoagulation with low molecular weight (LMW) heparin plus low-dose aspirin, in women with recurrent pregnancy loss associated with antiphospholipid antibodies (aPL).\n We examined 40 women with recurrent abortion (at least 3 occurrences) and repeatedly positive test results for anticardiolipin or lupus anticoagulant. The subjects were randomly assigned to treatment with IVIG or LMW heparin plus low-dose aspirin. Both therapies were started when the women were pregnant as documented by a positive urine test. IVIG was stopped at the thirty-first week of gestation, aspirin at the thirty-fourth week, and heparin at the thirty-seventh week. The primary outcome of interest was the rate of live births with the 2 treatments.\n The characteristics of the 2 groups were similar at the time of randomization. The women treated with LMW heparin plus low-dose aspirin had a higher rate of live births (84%) than those treated with IVIG (57%).\n Treatment with LMW heparin plus low-dose aspirin should be considered as the standard therapy for recurrent pregnancy loss due to aPL.", "We identified 19 women who had persistently positive test results for antiphospholipid antibodies who were considered to be at low risk because they had none of the associated signs or symptoms of the antiphospholipid antibody syndrome. They had had no (10/19, 53%) or just one prior spontaneous abortion and did not have a history of thrombosis or thrombocytopenia. Many (8/19, 42%) had had a prior uncomplicated pregnancy ending in a live birth. These women were randomly assigned to receive low-dose aspirin (81 mg daily) or usual care. There were few obstetric complications recorded in either treatment group. One woman in the aspirin group had a fetal death, and one in the usual care group had a low-birth-weight infant. The frequency of complications was so low that > 600 such women would need to be entered into a randomized trial to evaluate whether low-dose aspirin would be beneficial treatment during a pregnancy. We concluded that treatment of pregnant women with antiphospholipid antibodies who are otherwise at low risk cannot be justified on the basis of the available evidence.", "Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss.\n We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy.\n Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02).\n Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.", "nan", "We attempted to compare the use of low-dose heparin with a standard dose of 40 mg prednisone daily (both plus low-dose aspirin) for treatment of pregnant women with antiphospholipid antibody-associated recurrent fetal loss with respect to maternal and perinatal morbidity and efficacy in prevention of fetal death.\n A multicenter randomized trial included 20 patients. Generalizability of results from randomized patients was evaluated by means of additional data from 13 women refusing and 12 women ineligible for randomization. Data from study groups were compared with Fisher's exact test, and generalizability was evaluated with a chi 2 test for trend.\n Live birth rates were the same (75%) with either treatment, but \"serious\" maternal morbidity and the frequency of preterm delivery were significantly higher among women randomly assigned to prednisone (p = 0.02 vs p = 0.006). Preterm delivery among prednisone-treated women was usually associated with premature rupture of the membranes or preeclampsia. These results could be generalized to the other groups of women ascertained during the course of the study.\n Low-dose heparin should be preferred to prednisone when treatment is indicated for high-risk pregnant women with antiphospholipid antibodies.", "To compare the efficacy of low-dose aspirin alone versus low-dose aspirin plus low molecular weight heparin in pregnant women with antiphospholipid syndrome and recurrent miscarriage as prophylaxis against pregnancy loss.\n From a regional miscarriage clinic, 119 consecutive women with persistently positive tests for lupus anticoagulant and/or anticardiolipin immunoglobulin G and M antibody were invited to participate in a randomized, controlled trial between 1997 and 2000. After ethical approval and adherence to a written protocol, 12 women were unwilling to participate, five failed exclusion/inclusion criteria, and four were nonpregnant. Laboratory analysis was performed by Sheffield University Coagulation Department, electronically generated randomization by Manchester University Centre for Cancer Epidemiology, and data collection and analysis by a research officer at Leeds University. Viability ultrasound every 2 weeks was provided until 12 weeks' gestation before transfer to the pregnancy support antenatal clinic.\n Ninety-eight women were randomized before 12 weeks' gestation. Forty-seven received low-dose aspirin 75 mg daily (group A), and 51 received low-dose aspirin plus low molecular weight heparin 5000 U subcutaneously daily (group B) throughout pregnancy. There were 13 pregnancy losses and 34 live births in group A and 11 losses and 40 live births in group B. The live-birth rate was 72% in group A and 78% in group B (odds ratio 1.39, 95% confidence interval 0.55, 3.47). There were no cases of maternal thrombosis in either group.\n A high success rate is achieved when low-dose aspirin is used for antiphospholipid syndrome in pregnancy. The addition of low molecular weight heparin does not significantly improve pregnancy outcome.", "Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen.\n This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at </=12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate.\n Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 +/- 1.1 weeks; placebo group, 36.7 +/- 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 +/- 186.1 g; placebo group; 2604.4 +/- 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant.\n A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study." ]

[ "12205648", "15883262", "20200346" ]

[ "Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial.", "Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results.", "Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe." ]

[ "In a randomized, placebo-controlled, double-blind study, we investigated whether statins alter cholesterol metabolites and reduce Abeta levels in the cerebrospinal fluid of 44 patients with Alzheimer's disease. Individuals were given up to 80mg simvastatin daily or placebo for 26 weeks. Overall, simvastatin did not significantly alter cerebrospinal fluid levels of Abeta40 and Abeta42. In post hoc analysis, simvastatin significantly decreased Abeta40 levels in the cerebrospinal fluid of patients with mild Alzheimer's disease. The reduction of Abeta40 correlated with the reduction of 24S-hydroxycholesterol. These changes were not observed in more severely affected patients.", "Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder.\n To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease.\n Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment.\n Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable.\n The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels.\n Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward.\n Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.", "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." ]

[ "3323275", "3323274", "7131145", "10828633", "11576399", "11720074", "2305737", "2748470" ]

[ "Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis.", "Clinical studies with disposable diapers containing absorbent gelling materials: evaluation of effects on infant skin condition.", "Incidence of diaper rash when using cloth and disposable diapers.", "Continuous topical administration of a petrolatum formulation by a novel disposable diaper. 2. Effect on skin condition.", "Effects of breathable disposable diapers: reduced prevalence of Candida and common diaper dermatitis.", "Skin benefits from continuous topical administration of a zinc oxide/petrolatum formulation by a novel disposable diaper.", "Evaluations of diapers containing absorbent gelling material with conventional disposable diapers in newborn infants.", "Comparison of disposable diapers with fluff absorbent and fluff plus absorbent polymers: effects on skin hydration, skin pH, and diaper dermatitis." ]

[ "Cloth diapers, cellulose core diapers (conventional disposable diapers), and cellulose core diapers containing absorbent gelling material were examined for their effects on diaper rash and skin microbiology of normal infants and infants with atopic dermatitis in a 26-week double-blind clinical trial. Infants with atopic dermatitis wearing the diapers containing absorbent gelling material had significantly lower diaper rash grades than infants with atopic dermatitis wearing cloth diapers at five of eight grading visits. Infants with atopic dermatitis wearing conventional cellulose core diapers had statistically less rash at one of eight visits. There was no statistically significant difference between diaper types at three of the eight visits. At no time did the cloth group have less diaper rash than the conventional cellulose or absorbent gelling material disposable diaper group. A statistical correlation between the severity of general atopic dermatitis outside the diaper area and the diaper rash condition under the diaper occurred only in the atopic dermatitis group wearing cloth diapers. Isolation of microorganisms from the intact, uninvolved skin surface both inside and outside the diaper showed no biologically significant changes in the presence or numbers of selected skin organisms. Repeated isolation, at multiple grading visits of Staphylococcus aureus from uncompromised skin inside the diaper area was infrequent but correlated with the diagnosis of atopic dermatitis when observed.", "Disposable infant diapers with absorbent gelling material (cross-linked sodium polyacrylates) incorporated into the core were clinically evaluated for their effect on infant skin condition. Absorbent gelling materials tightly hold water and provide pH control by a buffering capacity as well as by helping to segregate urine apart from feces. Four clinical studies were conducted with each following a rigid protocol that controlled for variables of diet and age in addition to the diaper material that may influence the development of diaper dermatitis and helped to control for any inherent bias in the study. This allowed for the controlled assessment of skin condition with respect to diaper type. Absorbent gelling material-containing disposable, conventional (100% cellulose core) disposable, and home-laundered cloth diapers were test products. In these studies 1614 infants were initially enrolled with 522 of them assigned to absorbent gelling material disposable, 738 to conventional disposable, and 354 to home-laundered cloth diapers. Objective measurements of skin wetness (transepidermal water loss) and skin pH, as well as double-blind grading of diaper dermatitis, were the measures of skin condition. Absorbent gelling material disposable diapers were associated with significantly reduced skin wetness, closer to normal skin pH, and lower degrees of diaper dermatitis when compared to conventional disposable or home-laundered cloth diapers. The results are consistent with the hypothesis that better control in the diaper area of skin wetness, skin pH, and the prevention of the mixing of urine and feces produces a better diaper environment.", "nan", "Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have developed a novel diaper to deliver to the skin dermatological formulations intended to help protect the skin from overhydration and irritation.\n To determine the clinical benefits of a novel disposable diaper designed to deliver a petrolatum-based formulation continuously to the skin during use.\n Two independent, blinded, randomized clinical trials were conducted, involving an aggregate total of 391 children, 8-24 months of age. All comparisons were done versus a control diaper, identical to the test product except for the absence of the petrolatum formulation. The studies determined the effects of the novel diaper on skin erythema and diaper rash.\n Use of the formulation-treated diaper was associated with significant reductions in severity of erythema and diaper rash compared to the control product.\n The results demonstrated the clinical benefits associated with continuous topical administration of a petrolatum-based formulation by this novel diaper. We anticipate that this advance in diaper design will contribute significantly to further reduce the prevalence and severity of irritant contact dermatitis in the diaper area.\n Copyright 2000 S. Karger AG, Basel.", "Infants wearing breathable disposable diapers experienced significantly less diaper dermatitis (DD) compared to infants wearing standard, nonbreathable disposable diapers in a series of double-blind clinical trials. Severe DD, including confirmed infection with Candida albicans, was reduced by 38-50% among infants wearing highly breathable (HB) diapers. The prevalence of DD was inversely related to the breathability of the garments. The inhibitory effect of breathable diapers on the survival of Candida was further confirmed in controlled experiments with adult volunteers. A suspension of C. albicans cells was applied to delineated sites on the volar forearm. Each site was then covered by a full-thickness patch from either an HB or a standard diaper. Survival of Candida colonies was reduced by almost two-thirds in the breathable diaper-covered sites compared to the control sites.", "Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have advanced in our development of a novel diaper that delivers dermatological formulations to help protect the skin from over-hydration and irritation.\n To determine the clinical benefits of a novel disposable diaper designed to deliver a zinc oxide and petrolatum-based formulation continuously to the skin during use.\n All studies were independent, blinded, randomized clinical trials. Study A was conducted to confirm transfer of the zinc oxide/petrolatum (ZnO/Pet) formulation from the diaper to the child's skin during use. Children wore a single diaper for 3 h or multiple diapers for 24 h. After the use period, stratum corneum samples were taken from each child and analysed for ZnO/Pet. Study B evaluated the prevention of skin irritation and barrier damage from a standard skin irritant (SLS) in an adult arm model. Study C evaluated skin erythema and diaper rash in 268 infants over a 4-week usage period. One half of the infants used the ZnO/Pet diaper, while the other half used a control diaper that was identical except for the absence of the ZnO/Pet formulation.\n The ointment formulation and ZnO transferred effectively from the diaper to the child's skin during product use. Transfer of ZnO increased from 4.2 microg/cm2 at 3 h to > 8 microg/cm2 at 24 h. Exposure to the formulations directly on adult skin prior to an irritant challenge was associated with up to a 3.5 reduction in skin barrier damage and skin erythema. Greatest reductions were seen for the ZnO containing formulations. Wearing of the formulation treated diaper was also associated with a significant reduction in skin erythema and diaper rash compared to the control product.\n The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper.", "We evaluated 149 infants diapered in either conventional cellulose core disposable diapers or diapers containing cellulose core with absorbent gelling material. The infants were evaluated from 1 day of age to 14 weeks of age for the prevalence and severity of diaper dermatitis. We identified a low prevalence of diaper dermatitis throughout the study period. At 14 weeks of age, we noted that infants in diapers containing absorbent gelling material had significantly less diaper dermatitis than those in conventional disposable diapers. Despite the overall low prevalence of diaper dermatitis in the newborn period, 7 of 204 infants evaluated had small skin erosions in the diaper area noted within the first 4 days of age. Both diaper types were associated with infants with erosions. This surprisingly high incidence of erosions in newborn infants suggests previously undocumented increased skin fragility of full-term infants.", "Diaper dermatitis results from the action of a number of physical and chemical factors on the skin. While its etiology is complex, there is agreement that prolonged contact between wet diapers and the skin leading to excessive hydration of the stratum corneum and reduced barrier function is a primary factor. Recent research also indicates that pH elevation resulting from ammonia production increases the probability of skin damage due to fecal enzyme activity. New diapers containing absorbent polymers blended with cellulose fluff in the absorbent core have been developed. The absorbent polymer binds fluids and controls pH in the diaper environment. To assess the effectiveness of these diapers, a clinical study was conducted with approximately 150 infants over 15 weeks, using fluff diapers and absorbent polymer diapers. The results clearly showed that the diapers with absorbent polymer provide a better skin environment than those with fluff only with respect to lower skin wetness and pH control (instrumental measurements). In addition, the clinicians' grades indicated a directional reduction in diaper rash severity." ]

[ "18442423", "1512910", "20142693", "18608367", "3335558", "16445331", "1471839", "8615108" ]

[ "Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.", "A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.", "Use of inpatient continuous passive motion versus no CPM in computer-assisted total knee arthroplasty.", "Continuous passive motion as an adjunct to active exercises in early rehabilitation following total knee arthroplasty - a randomized controlled trial.", "Deep-vein thrombosis and continuous passive motion after total knee arthroplasty.", "Effectiveness of continuous passive motion and conventional physical therapy after total knee arthroplasty: a randomized clinical trial.", "Beneficial effects of continuous passive motion after total condylar knee arthroplasty.", "Continuous passive motion compared to active physical therapy after knee arthroplasty: similar hospitalization times in a randomized study of 68 patients." ]

[ "Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered.\n In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee.\n Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments.\n Although results indicate that prolonged CPM use might have a small short-term effect on RoM, routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered, since neither long-term effects nor transfer to better functional performance was detected.\n ISRCTN85759656.", "To evaluate the efficacy of continuous passive motion (CPM) in the postoperative management of patients undergoing total knee arthroplasty.\n A randomized controlled single-blind trial of CPM plus standardized rehabilitation vs standard rehabilitation alone.\n A referral hospital for arthritis and musculoskeletal care.\n Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion. One hundred fifty-four patients were eligible and 102 patients agreed to participate and were randomized. Ninety-three patients completed the study protocol.\n Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with standardized rehabilitation program compared with standardized rehabilitation program alone.\n Primary outcomes were pain, active and passive knee range of motion, swelling (or circumference), quadriceps strength at postoperative day 7, as well as complications, length of stay, and active and passive range of motion and function at 6 weeks.\n Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain, active and passive extension, quadriceps strength, or length of hospital stay. At 6 weeks there were no differences between the two groups in either range of motion or function. In this series, use of CPM resulted in a net savings of $6764 over conventional rehabilitation in achieving these results.\n For the average patient undergoing total knee arthroplasty, CPM is more effective in improving range of motion, decreasing swelling, and reducing the need for manipulation than is conventional therapy and lowers cost.", "Continuous passive motion (CPM) has shown positive effects on tissue healing, edema, hemarthrosis, and joint function (L. Brosseau et al., 2004). CPM has also been shown to increase short-term early flexion and decrease length of stay (LOS) ( L. Brosseau et al., 2004; C. M. Chiarello, C. M. S. Gundersen, & T. O'Halloran, 2004). The benefits of CPM for the population of patients undergoing computer-assisted total knee arthroplasty (TKA) have not been examined.\n The primary objective of this study was to determine whether the use of CPM following computer-assisted TKA resulted in differences in range of motion, edema/drainage, functional ability, and pain.\n This was an experimental, prospective, randomized study of patients undergoing unilateral, computer-assisted TKA. The experimental group received CPM thrice daily and physical therapy (PT) twice daily during their hospitalization. The control group received PT twice daily and no CPM during the hospital stay. Both groups received PT after discharge. Measurement included Knee Society scores, Western Ontario McMaster Osteoarthritis Index values, range of motion, knee circumference, and HemoVac drainage. Data were collected at various intervals from preoperatively through 3 months.\n Although the control group was found to be higher functioning preoperatively, there was no statistically significant difference in flexion, edema or drainage, function, or pain between groups through the 3-month study period.", "Continuous passive motion is frequently used post-operatively to increase knee range of motion after total knee arthroplasty in spite of little conclusive evidence. The aim of this study was to examine whether continuous passive motion (CPM) as an adjunct to active exercises had any short time effects (after one week and three months) on pain, range of motion, timed walking and stair climbing.\n A randomized controlled trial was conducted. A total of 63 patients undergoing primary TKA were randomly assigned into an experimental group receiving CPM and active exercises and a control group receiving active exercises only. Outcomes were assessed by goniometer, visual analogue scale (VAS), timed 'Up and Go' test (TUG), timed 40 m walking distance and timed stair climbing.\n There were no statistical differences between the treatment groups for any outcome measures either at one week or after three months. For the whole group, a significant and 50% reduction in pain score was found after three months (p < 0.01). Compared with before surgery, a significantly impaired knee flexion range of motion (p < 0.01) and a significantly decreased number of patients able to climb stairs were found after three months (p < 0.01).\n CPM was not found to have an additional short-time effect compared with active physiotherapy. After three months considerable pain relief was obtained for the whole group, the patients preoperative ROM was not restored and the number of patients able to climb stairs had decreased.", "Seventy-five of 150 consecutive patients who underwent total knee arthroplasty had routine physiotherapy and seventy-five had continuous passive motion of the lower limb that had been operated on as well as routine physiotherapy. A pulmonary embolus did not develop in any patient, but about 40 per cent had thrombosis in the veins of the calf, whether passive motion had been administered or not. Radiographically, the deep-vein thrombosis was seen to extend into or proximal to the popliteal vessel in 5 per cent of the patients in each group. Sex, age, obesity, or a history of hypertension or diabetes did not influence the incidence of venous thrombosis, but there was a higher incidence in patients in whom cement was used for fixation of the total knee components, irrespective of the use of continuous passive motion of the limb.", "This randomized clinical trial was conducted to compare the effectiveness of 3 in-hospital rehabilitation programs with and without continuous passive motion (CPM) for range of motion (ROM) in knee flexion and knee extension, functional ability, and length of stay after primary total knee arthroplasty (TKA).\n Eighty-one subjects who underwent TKA for a diagnosis of osteoarthritis were recruited.\n All subjects were randomly assigned to 1 of 3 groups immediately after TKA: a control group, which received conventional physical therapy intervention only; experimental group 1, which received conventional physical therapy and 35 minutes of CPM applications daily; and experimental group 2, which received conventional physical therapy and 2 hours of CPM applications daily. All subjects were evaluated once before TKA and at discharge. The primary outcome measure was active ROM in knee flexion at discharge. Active ROM in knee extension, Timed \"Up & Go\" Test results, Western Ontario and McMaster Universities Osteoarthritis Index questionnaire scores, and length of stay were the secondary outcome measures.\n The characteristics of and outcome measurements for the subjects in the 3 groups were similar at baseline. No significant difference among the 3 groups was demonstrated in primary or secondary outcomes at discharge.\n The results of this study do not support the addition of CPM applications to conventional physical therapy in rehabilitation programs after primary TKA, as applied in this clinical trial, because they did not further reduce knee impairments or disability or reduce the length of the hospital stay.", "A randomised, controlled study of the use of postoperative continuous passive motion (CPM) and immobilisation regimen after total condylar knee arthroplasty was performed. CPM resulted in a significant increase in both the early and late range of knee flexion. This increase occurred in both rheumatoid and osteoarthritic patients. The improvement of 10 degrees at 12 months allowed additional important function to be attained. CPM resulted in significantly earlier discharge from hospital. It did not increase the clinical incidence of wound healing problems, nor did it significantly increase the postoperative fixed flexion deformity or the extension lag. CPM can be recommended as a safe and effective modality to achieve more rapid and more successful postoperative rehabilitation after knee arthroplasty.", "68 consecutive patients who had primary knee arthroplasties because of arthrosis were randomized to postoperative continuous passive motion (CPM) or active physical therapy (APT). Rehabilitation in both groups was initiated on the first postoperative day. The CPM group sustained less postoperative knee swelling with more rapid initial improvement in knee flexion than did the APT group, but there were no differences between the groups in knee flexion at discharge. Postoperative pain rating and hospitalization times were similar in the two groups." ]

[ "2085966", "3842217", "11145369", "6839761", "12319865", "7128130", "428219", "1893708", "3881295", "17303485", "1844327", "6351364", "6351363", "3219853", "2491981", "7495202", "8200217", "7942261", "7859451", "7491853", "2257739" ]

[ "The TCu380A, TCu220C, multiload 250 and Nova T IUDS at 3,5 and 7 years of use--results from three randomized multicentre trials. World Health Organization. Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on the Safety and Efficacy of Fertility Regulating Methods.", "Postabortion insertion of the Nova T and MLCu250: preliminary results of a comparative study.", "Comparison of the performances of TCu380A and TCu380S IUDs up to five years.", "A randomised comparative evaluation of the copper 7, multiload copper 250 and T copper-22OC IUDs.", "A comparative study of the TCu 380A versus TCu 200 IUDs in Nepal.", "Interval iud insertion in parous women: a randomized multicentre comparative trial of the Lippes Loop D, TCu220c and the Copper 7.", "Randomized comparison of clinical performance of two copper-releasing IUDs, Nova-T and Copper-T-200, in Denmark, Finland and Sweden.", "A comparative clinical trial of the TCu 380A, Lippes Loop D and Multiload Cu 375 IUDs in Indonesia.", "An evaluation of the TCu 380Ag and the Multiload Cu375.", "A randomized trial on the clinical performance of Nova T380 and Gyne T380 Slimline copper IUDs.", "Clinical performance of intrauterine devices in nulligravidae: is the length of the endometrial cavity of significance?", "IUD insertion following termination of pregnancy: a clinical trial of the TCu 220C, Lippes loop D, and copper 7.", "IUD insertion following spontaneous abortion: a clinical trial of the TCu 220C, Liuppes loop D, and copper 7.", "A three-year evaluation of TCu 380 Ag and multiload Cu 375 intrauterine devices.", "Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD.", "Performances of copper T 380A and multiload copper 375/250 intrauterine contraceptive devices in a comparative clinical trial.", "Contraceptive efficacy of the Copper T 380A and Copper T 200 intrauterine devices: results from a comparative clinical trial in six developing countries.", "Contraceptive efficacy of the Copper T380A and the Multiload Cu250 IUD in three developing countries.", "Clinical performance of the TCu 380A and TCu 220C IUDs in four developing country family planning clinics.", "A randomized comparative study of the TCu380A and Cu-Safe 300 IUDs.", "A randomized trial of the Gyne T 380 and Gyne T 380 Slimline Intrauterine Copper devices." ]

[ "The WHO Special Programme of Research, Development and Research Training in Human Reproduction has conducted between 1979 and the present, three randomized comparative clinical trials of the TCu220C, Multiload 250, Nova T and TCu380A devices in 24 centres in 14 countries. The comparative study of the TCu220C and the Multiload 250 devices was completed after three years of use with no significant differences in event rates between the devices (three-year cumulative pregnancy rates of 1.7% and 2.8%, respectively). The Nova T device was discontinued from the comparative study with the TCu220C after five years of use having shown significantly higher cumulative pregnancy rates at three and at five years of use-6.6% and 12.3%, respectively, compared to 4.4% and 6.6%, respectively, for the TCu220C. In the comparative study of the TCu220C and TCu380A, the latter device had significantly lower cumulative pregnancy rates of 1.0%, 1.4% and 1.6% at three, five and seven years of use, respectively (comparative results for the TCu220C: 3.4%, 4.0% and 4.9%, respectively). It is suggested that the TCu380A life span be extended to at least seven years of use and the device be considered as a non-surgical, potentially reversible, alternative to tubal ligation for women needing long-term fertility regulation.", "This 4-year prospective randomized study is designed to compare the effectiveness and complication rates of the Nova T and MLCu250 inserted immediately postabortion. At the cut-off date (30 November 1983), all patients in the first cohort of 400 women had completed at least 12 months of use. At this stage of the trial, no significant differences had emerged between the two devices in any of the standard termination categories.", "A modification of the TCu380A IUD to create the model TCu380S was introduced many years ago. The TCu380S utilizes copper sleeves that are flush in the plastic and are set at both ends of the horizontal arm. The objective of this study is to compare the clinical performance of the TCu380A and the TCu380S IUDs, especially regarding contraceptive performance and expulsion, in a cohort of women who had one of these two devices inserted at random. This paper presents the results up to 5 years of use. A total of 1568 women were enrolled: 806 women received a TCu380A and 762 women received a TCu380S IUD. The performance was evaluated by life-table analysis and significance between rates was tested by the method of log-rank. The cumulative pregnancy rate was low in users of both models of IUD but lower in users of the TCu380S model through the 5 years of use, without statistical significance. Expulsion was significantly higher in users of the TCu380S model during the five years of use. The other reasons for discontinuation were similar for both devices and did not show statistical significance. The continuation rate was significantly lower in users of the TCu380S model in the first and second years of use. Both devices presented a very low pregnancy rate and TCu380S presented a lower pregnancy rate than the TCu380A, although without statistical significance.", "Two new Cu-IUDs, the TCu-22OC and Multiload Cu250, were evaluated against the Cu7 in 1,199 subjects in a randomised, multicentric trial using a common study protocol. During the 2 years following insertion, cumulative first-segment rates for total use-related terminations showed no significant differences between the 3 devices; however, the Cu7 had a significantly higher termination rate for accidental pregnancy compared to the TCu-22OC and its expulsion rate was significantly higher than the ML Cu250. The rate of accidental pregnancy was higher and the expulsion rate lower with the ML Cu250 compared to the TCu-22OC but these differences were not significant. The results are discussed in relation to IUD design and their application in family planning.", "nan", "A multicentre randomized clinical trial of the TCu220C, Lippes Loop D and Copper 7 was undertaken in nine WHO Collaborating centres for Clinical Research in Human Reproduction. A total of 984, 992 and 994 devices, respectively, were inserted between 1976 and 1978. The subjects were followed for two years. At this time 18,743, 17,013 and 17,927 woman-months experience had been accumulated with each device, respectively. The Lippes Loop consistently failed to perform as well as the TCu220C regardless of age or parity. The TCu220C had statistically significantly lower pregnancy rates at one and two years of use than either of the other two devices as well as lower expulsion rates. The TCu220C had lower removal rates at one and two years than the Lippes Loop and Copper 7. At one and two years the TCu220C had significantly higher continuation rates than the other two devices. It is concluded that the TCu220C is the device of choice amongst the three devices studied.", "A randomized study was conducted simultaneously in three countries to compare the clinical performance of two new IUDs, the Nova-T and Copper-T-200. Forty-four persons, midwives, general practitioners, residents and specialists in obstetrics and gynecology inserted 907 Nova-Ts and 936 Copper-Ts. The pregnancy rate of Nova-T (0.7 at one year) was significantly lower than that of Copper-T (2.2 at one year). No significant differences were observed in other termination rates. The continuation rates were 72.6 for Nova-T and 71.3 for Copper-T-200. The total experience was based on 18,035 woman months of use, with a lost to follow-up of less than 7 per cent for both IUDs.", "The Copper T 380A (TCu 380A), Lippes Loop D (LLD) and the Multiload Cu 375 (MLCu 375) IUDs were evaluated for safety and efficacy in a multicenter randomized clinical trial in Indonesia. A total of 2992 women were enrolled into the study and data for 2845 women were analyzed (147 cases did not meet protocol criteria). Although study IUDs were randomly assigned, LLD users in this study were older and of higher parity than TCu 380A and MLCu 375 users. The 24-month gross cumulative life-table pregnancy rates for TCu 380A, LLD and MLCu 375 users were 1.2, 2.2 and 2.7, respectively. The 24-month expulsion rates for TCu 380A, LLD and MLCu 375 users were 6.7, 7.5 and 5.3, respectively. Overall, 24-month continuation rates were 85.5%, 85.0% and 85.4% for the respective device groups. Differences in both gross and age- and parity-adjusted life-tables rates for the major outcome variables were not statistically significant at 24 months postinsertion. The study suggests that the TCu 380A, LLD and MLCu 375 IUDs seem to be safe and effective contraceptive options for Indonesian women.", "The TCu 380Ag (Outokumpu Oy, Pori, Finland) and the Multiload Cu375 (Multilan, Organon, Oss, The Netherlands) were evaluated in 1477 women in a multicenter clinical trial. The intrauterine devices showed similar, low-event rates. Cumulative life-table pregnancy rates were less than 1.0, and continuation rates were approximately 90 per 100 women at 1 year after insertion. The risk of subsequent hospitalization or pelvic infection was low.", "The objective of this open randomized study was to compare the clinical performance of Nova T380 and Gyne T380 Slimline copper intrauterine devices (IUDs).\n Eligible for analyses were 957 Norwegian parous women aged 18-45 years. Clinical performance was measured upon the removal of IUD due to contraceptive failure, expulsion, bleeding, pain, pelvic inflammatory disease and other medical reasons during a 5-year study period.\n The discontinuation rate due to contraceptive failure was significantly higher in the first year for Nova T380 users than for Gyne T380 Slimline users, whereas no differences were observed thereafter (the 5-year cumulative failure rates were 4.4% and 2.2%, respectively, per 100 women). However, the partial expulsion rate was significantly higher in the first year for Gyne T380 Slimline users than for Nova T380 users (the 5-year cumulative rates were 3.4% and 1.1,% respectively, per 100 women). No other major differences in reasons for discontinuation were found between the study groups. There was a slight nonsignificant increase in hemoglobin levels for both study groups over the course of the study.\n Clinical performance was considered satisfactorily high for both devices.", "In a double-blind study 236 nulligravidae were randomized to insertion of standard models of two commonly used intrauterine devices, Multiload and Gravigard, or shorter versions of these devices. Before insertion the total axial uterine length and the length of the endometrial cavity were determined. After 12 months the total continuation rate was 57.2%. The clinical performance of Multiload models was not statistically different from that of the Gravigards, and the short IUD-types did not do better than the longer ones. Among the longer models a significant higher continuation rate was observed with the Multiload. The frequency of side effects was not increased when the total uterine cavity length was less than 7 cm. As the incidence of side effects was higher than normally reported after insertion of IUD's in parous women it is concluded that insertion of IUD's in nulligravidae should be performed only when other methods of contraception are unacceptable. The ratio between the lengyh of the uterine cavity and the length of the IUD seems to be of no significance for the clinical events following insertion of IUD's in nulligravidae.", "nan", "nan", "A randomized, comparative, multicenter clinical trial of TCu 380Ag and Multiload Cu 375 intrauterine devices (IUDs) was conducted. Safety and acceptability were evaluated through three years following insertion in 884 patients. The two IUDs were similar with respect to all event rates. Thirty-six month life table pregnancy rates were 0.6 per 100 TCu 380Ag users and 1.8 per 100 Multiload Cu 375 users. Continuation rates were 67.4 and 61.4 per 100 users of the respective devices at three years after insertion.", "A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.", "An evaluation of the performances of copper T 380A (TCU 380A) and multiload copper 375/250 (MLCU 375/250) intrauterine contraceptive devices (IUCDS) was carried out at University College Hospital, Ibadan, Nigeria (UCH) in a clinical comparative trial. The IUCDS showed similar low vent rates at one year of continuous use. The difference in cumulative net probabilities for termination due to pelvic inflammatory disease was weakly significant at the sixth month of follow up with MLCU 250 having the highest rate. (TCU 380A-0%; MLCU 375-0%; MLCU 250-3.1%; X2 = 6.0; P < 0.05). This significant difference disappeared by the twelfth month of continuous use. Likewise, the difference in cumulative net probabilities for overall termination was significant at six months and insignificant at twelve months of follow up. The continuation rate after one year were 86%, 92% and 87% respectively for TCU 380A, MLCU 375 and MLCU 250. These rates were higher than 80% and 51% quoted for the previously available Lippes loop in the same environment [1,2]. It was therefore concluded that the three IUCDS are comparable in performances in the first year of use and could be used at our family planning clinic or any other clinic in a similar setting.", "The clinical performance of the Copper T 380A (TCu 380A) and the Copper T 200 (TCu 200) intrauterine devices (IUDs) was evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a multicenter randomized clinical trial at one site in each of six developing countries. The pregnancy rate with the TCu 380A IUD was significantly lower than the pregnancy rate with the TCu 200 IUD at 12 months (0.5 and 2.6 per 100 women, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regards to expulsion or removals due to bleeding/pain, personal, medical, or planned pregnancy. The TCu 380A IUD did not have a disproportionately higher incidence of side effects such as intermenstrual bleeding or pain, inflammations or infections, or insertion-related events compared to the TCu 200 IUD. TCu 380A IUD users, however, were significantly more likely to report increased dysmenorrhea than were TCu 200 IUD users. The performance of the TCu 380A IUD in preventing pregnancy during this trial indicates that this IUD may be a better option than the TCu 200 IUD for women wishing to practice effective, long-term, reversible birth control without having to resort to hormonal methods.", "The clinical performance of the Copper T380A (TCu380A) and the Multiload 250 (MLCu250) intrauterine devices (IUDs) were evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at four collaborating research sites located in three developing countries. The gross cumulative life-table pregnancy rate of the TCu380A IUD was significantly lower than the rate with the MLCu250 IUD at 12 months (0.5 and 1.2, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regard to IUD expulsion or IUD removal due to bleeding/pain, personal reasons, medical reasons, or planned pregnancy. TCu380A IUD users were more likely to report experiencing increased dysmenorrhea (p < 0.01) or intermenstrual pelvic pain (p < 0.01) than were MLCu250 IUD users. However, few of these users discontinued use of their assigned IUD because of having experienced menstrual bleeding disturbances or intermenstrual pelvic pain. These data indicate that the TCu380A IUD may be a better option than the MLCu250 IUD for women wishing to practice highly effective long-term birth control without having to resort to hormonal methods.", "The clinical performance of the Copper T 380A (TCu 380A) and the Copper T 220C (TCu 220C) intrauterine devices (IUDs) were evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at four collaborating research sites located in two developing countries. The gross cumulative life-table pregnancy rate of the TCu 380A IUD was found to be lower than that of the TCu 220C IUD at 12 months (0.3 and 0.8, respectively), although this difference was not statistically significant (p > 0.05). Statistically significant differences between the two study IUDs were not found with regard to IUD expulsion or IUD removal due to bleeding/pain, personal reasons, medical reasons, or planned pregnancy. No statistically significant differences were observed in the frequency of experiencing menstrual disturbances (i.e., dysmenorrhea, intermenstrual pelvic pain or intermenstrual bleeding) between the two IUD groups. These data suggest that the TCu 380A and TCu 220C IUDs are both appropriate options for contracepting women. The TCu 380A IUD, however, may be a more appropriate option for those women wishing to space births over a longer period of time.", "The Cu-Safe 300 is one of the latest additions to the array of available IUDs. It was specifically designed to decrease unwanted side-effects (e.g. bleeding, pain and expulsion) while providing simplicity of insertion, ease of removal and fair contraceptive protection. For comparison, the TCu380A was chosen. Both types were inserted at random in 600 recipients by a group of independent physicians with a long standing experience in intrauterine contraception. Life table analysis was used for comparison over a period of three years. The Cu-Safe 300 produced a slightly but not statistically significant higher pregnancy rate and more expulsions. Removals for bleeding and pain, however, were significantly less frequent. All inserting physicians agreed that insertion and removal of this new device was remarkably easy.", "To facilitate manufacture and insertion of the Gyne T 380 IUD, design changes were instituted. Copper collars were seated flush at the ends of the horizontal crossbar of the device. A randomized study of the Gyne T 380 Slimline, the new design, was undertaken in comparison with the standard Gyne T 380. A total of 996 women were enrolled, with 698 Slimline insertions and 298 of the standard Gyne T. No statistically significant difference in ease of insertion or in performance was detected between the models. At one year, the pregnancy rate of each model was below 0.5 per 100 and the continuation rate was 79-80 per 100. Pelvic inflammatory disease or endometritis was found in one percent of subjects in the first year. This is the seventh multicenter randomized study of a collared T IUD with 380 mm2 of copper surface. In all seven, the one-year gross pregnancy rate has been 1.2 per 100 or lower." ]

[ "15966880", "15016039", "16489947", "10397519", "15998268", "16856902", "16512765" ]

[ "Effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise ultrasonic debridement.", "Quadrant root planing versus same-day full-mouth root planing. I. Clinical findings.", "Clinical outcomes of quadrant root planing versus full-mouth root planing.", "One stage full- versus partial-mouth disinfection in the treatment of chronic adult or generalized early-onset periodontitis. I. Long-term clinical observations.", "Full-mouth ultrasonic debridement versus quadrant scaling and root planing as an initial approach in the treatment of chronic periodontitis.", "Benefit of \"one-stage full-mouth disinfection\" is explained by disinfection and root planing within 24 hours: a randomized controlled trial.", "Periodontal debridement with povidone-iodine in periodontal treatment: short-term clinical and biochemical observations." ]

[ "The aim of this randomized controlled clinical trial was to determine the effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise therapy.\n Thirty-six subjects with chronic periodontitis, were randomly allocated to three groups--quadrant-wise ultrasonic debridement, single-visit full-mouth ultrasonic debridement with povidone iodine and single-visit full-mouth ultrasonic debridement with water. Whole-mouth plaque, bleeding on probing (BOP), pocket depth and attachment level were recorded before treatment and 1, 3 and 6 months post-treatment. Plaque and saliva samples were collected for microbiological analysis.\n After treatment, all groups showed significant improvement in clinical parameters. Full-mouth treatments resulted in similar improvements in full-mouth mean plaque percentage, probing pocket depth and probing attachment level as conventional therapy. When data were analysed based on pocket depth and tooth type, there was no difference between groups in probing depth reduction or attachment gains. The full-mouth groups demonstrated greater reduction in BOP% and number of pockets > or =5 mm and the total treatment time was significantly shorter. The detection frequencies of periodontal pathogens in plaque and saliva showed slight changes with no difference between groups.\n Single-visit full-mouth mechanical debridement may have limited additional benefits over quadrant-wise therapy in the treatment of periodontitis, but can be completed in a shorter time.", "The aim of this study was to test the hypothesis that same-day full-mouth scaling and root planing (FM-SRP) resulted in greater clinical improvement compared to quadrant scaling and root planing (Q-SRP) in chronic periodontitis patients over a period of 6 months.\n Forty patients were recruited into this study. Subjects were randomised into two groups. The FM-SRP group received full-mouth scaling and root planing completed within the same day, while the Q-SRP group received quadrant root planing at 2-weekly intervals over four consecutive sessions. Whole-mouth clinical measurements were recorded with a manual periodontal probe at baseline (BAS) and at reassessment 1 (R1) (approximately 6 weeks after the completion of therapy), and at reassessment 2 (R2) (6 months after the initiation of therapy). Selected site analyses were performed on the deepest site in each quadrant before and after therapy (R1 and R2) and clinical indices were recorded with an electronic pressure sensitive probe. In addition, during the active phase of treatment clinical data were collected at 2-weekly intervals from the remaining untreated quadrants in the Q-SRP group only.\n Both therapies resulted in significant improvements in all clinical indices both at R1 and R2. A continuous clinical improvement was seen for both treatment groups during the experimental period, which reached peak levels at 6 months (DeltaPD=1.8 mm, DeltaCAL=1.1 mm, p<0.001; PD: pocket depth; CAL: clinical attachment level). The selected-site analysis revealed no significant differences in any clinical index between the two treatment groups at R2 (DeltaPD=2.8 mm, DeltaRAL=1.1 mm; RAL: relative attachment level). At the selected sites, the analysis of the deep pockets (>7 mm) showed a significantly greater gain in RAL for the FM-SRP group compared to the Q-SRP group at R2 (p<0.05). The results of this analysis however, should be interpreted with care due to the small number of deep pockets. Data from the Q-SRP group provided an insight into how treated and untreated quadrants responded during the initiation of plaque control measures. There were significant reductions in PD, suppuration (SUP), modified gingival index (MGI) and plaque index (PI) in the remaining untreated quadrants in the Q-SRP group during the initial phase of treatment (p<0.05), while minimum changes in RALs and bleeding on probing (BOP) occurred. Nevertheless, the improvement in PD was clearly inferior to that seen after scaling and root planing.\n Following both therapeutic modalities, there were marked clinical improvements at both R1 and R2 (6 months) from baseline. The current study, in contrast to previous findings, failed to show that FM-SRP is a more efficacious periodontal treatment modality compared to Q-SRP. However, both modalities are efficacious and the clinician should select the treatment modality based on practical considerations related to patient preference and clinical workload.\n Copyright Blackwell Munksgaard, 2004.", "To determine the clinical effects of full mouth compared with quadrant wise scaling and root planing.\n Twenty patients with chronic periodontitis (> or = 2 teeth per quadrant with probing pocket depths (PPD) > or = 5 mm and bleeding on probing (BOP) were randomized into a test group treated in two sessions with subgingival scaling and root planing within 24 h (full-mouth root planing (FMRP)) and a control group treated quadrant by quadrant in four sessions in intervals of 1 week (quadrant root planing (QRP)). PPD, relative attachment level (RAL) and BOP were recorded at baseline, 3 and 6 months.\n Analysing first quadrant data, in moderately deep pockets (5 mm < or = PPD < 7 mm) there was no evidence for a difference (FMRP-QRP) between both groups for PPD reduction (mean: -0.128 mm; CI: [-0.949, 0.693]; p=0.747), RAL gain (mean: 0.118 mm; CI: [-0.763, 1.000]; p=0.781), and BOP reduction (mean: -20.1%; CI: [-44.3, 4.2]; p=0.099). Likewise, no significant differences between treatments were found for initially deep pockets (PPD > or = 7 mm), neither for first quadrant nor for whole mouth data.\n The results of the present study demonstrated equally favourable clinical results following both treatment modalities.", "A standard treatment strategy for periodontal infections often consists of 4 consecutive sessions of scaling and root planing (per quadrant, at 1- to 2-week intervals), without proper disinfection of the remaining intra-oral niches for periodontopathogens. This could theoretically lead to a reinfection of previously disinfected pockets by bacteria from an untreated region/niche. This study aimed to investigate, over an 8-month period, the clinical benefits of a one stage full-mouth disinfection in the control of severe periodontitis.\n Sixteen patients with early-onset periodontitis and 24 patients with severe adult periodontitis were randomly assigned to test and control groups. The control group was scaled and root planed, per quadrant, at 2-week intervals and given standard oral hygiene instructions. A one stage full-mouth disinfection (test group) was sought by scaling and root planing the 4 quadrants within 24 hours in combination with the application of chlorhexidine to all intra-oral niches for periodontopathogens. Besides oral hygiene, the test group also rinsed twice daily with a 0.2% chlorhexidine solution and sprayed the tonsils with a 0.2% chlorhexidine spray, for 2 months. The plaque index, gingival index, probing depth, bleeding on probing, gingival recession, and clinical attachment level were recorded at baseline and at 1, 2, 4, and 8 months afterwards.\n The one stage full-mouth disinfection resulted, in comparison to the standard therapy, in a significant (P <0.001) additional probing depth reduction and gain in attachment up to 8 months. For initial pockets > or =7 mm, the \"additional\" probing depth reduction at the 8 month follow-up was 1.2 mm for single-rooted and 0.9 mm for multi-rooted teeth, with corresponding additional gains in attachment of 1.0 mm and 0.8 mm, respectively. The additional improvements were observed for all subgroups (adult periodontitis, generalized early-onset cases, smokers), with the largest differences in the non-smoking adult periodontitis patients.\n These findings suggest that a one stage full-mouth disinfection results in an improved clinical outcome for the treatment of chronic adult or early-onset periodontitis as compared to scaling and root planing per quadrant at 2-week intervals.", "To evaluate the clinical efficacy of (i) a single session of \"full-mouth ultrasonic debridement\" (Fm-UD) as an initial periodontal treatment approach and (ii) re-instrumentation of periodontal pockets not properly responding to initial subgingival instrumentation. Methods: Forty-one patients, having on the average 35 periodontal sites with probing pocket depth (PPD) > or =5 mm, were randomly assigned to two different treatment protocols following stratification for smoking: a single session of full-mouth subgingival instrumentation using a piezoceramic ultrasonic device (EMS PiezonMaster 400, A+PerioSlim tips) with water coolant (Fm-UD) or quadrant scaling/root planing (Q-SRP) with hand instruments . At 3 months, all sites with remaining PPD> or =5 mm were subjected to repeated debridement with either the ultrasonic device or hand instruments. Plaque, PPD, relative attachment level (RAL) and bleeding following pocket probing (BoP) were assessed at baseline, 3 and 6 months. Primary efficacy variables were percentage of \"closed pockets\" (PPD< or =4 mm), and changes in BoP, PPD and RAL.\n The percentage of \"closed pockets\" was 58% at 3 months for the Fm-UD approach and 66% for the Q-SRP approach (p>0.05). Both treatment groups showed a mean reduction in PPD of 1.8 mm, while the mean RAL gain amounted to 1.3 mm for Fm-UD and 1.2 mm for Q-SRP (p>0.05). The re-treatment at 3 months resulted in a further mean PPD reduction of 0.4 mm and RAL gain of 0.3 mm at 6 months, independent of the use of ultrasonic or hand instruments. The efficiency of the initial treatment phase (time used for instrumentation/number of pockets closed) was significantly higher for the Fm-UD than the Q-SRP approach: 3.3 versus 8.8 min. per closed pocket (p<0.01). The efficiency of the re-treatment session at 3 months was 11.5 min. for ultrasonic and 12.6 min. for hand instrumentation (p>0.05).\n The results demonstrated that a single session of Fm-UD is a justified initial treatment approach that offers tangible benefits for the chronic periodontitis patient.", "The beneficial effects of the one-stage, full-mouth disinfection remain controversial in the scientific literature. This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing. This parallel, single blind RCT study aimed to compare several full-mouth treatment strategies with each other.\n Seventy-one patients with moderate periodontitis were randomly allocated to one of the following treatment strategies: scaling and root planing, quadrant by quadrant, at two-week intervals (negative control, NC), full-mouth scaling and root planing within 2 consecutive days (FRP), or three one-stage, full-mouth disinfection (FM) protocols within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics: chlorhexidine (FMCHX) for 2 months, amine fluoride/stannous fluoride for 2 months (FMF), or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months (FMCHX+F). At baseline and after 2, 4, and 8 a series of periodontal parameters were recorded.\n All treatment strategies resulted in significant (p<0.05) improvements of all clinical parameters over the entire duration of the study. Inter-treatment differences were often encountered. The NC group nearly always showed significant smaller improvements than the two CHX groups. The differences between the FRP or FM groups, and the two CHX groups only sporadically reached a statistical significance.\n These observations indicate that the benefits of the \"OSFMD\" protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time.", "The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument, associated with 0.5% povidone (pvp)-iodine irrigation in patients with chronic periodontitis.\n Forty-five patients were randomly assigned into three groups: the control group (CG) received quadrant root planing at 1-week intervals over four consecutive sessions; the periodontal debridement plus pvp-iodine group (PD-PIG) received a 45-minute full-mouth debridement with an ultrasonic instrument, associated with 0.5% pvp-iodine irrigation; and the periodontal debridement group (PDG) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument, associated with NaCl irrigation.\n At the 3-month evaluation, the mean probing depth (PD) reduction in CG was 2.51+/-0.52 mm, 2.53+/-0.50 mm in PD-PIG, and 2.58+/-0.60 mm in PDG (P<0.05). The clinical attachment level (CAL) analysis showed a statistically significant gain in all groups compared to baseline (1.87+/-0.56 mm [CG], 1.94+/-0.70 mm [PD-PIG], and 1.99+/-0.92 mm [PDG]). Intergroup analysis of PD and CAL at 1 and 3 months showed no differences (P>0.05). The N-benzoyl-L-arginine-p-nitroanilide (BAPNA) test showed a significant reduction in trypsin activity only during the first month (P<0.05); at 3 months there were no differences compared to baseline (P=0.80).\n This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement." ]

[ "4605009" ]

[ "Rapid tranquilization of acutely psychotic patients with intramuscular haloperidol and chlorpromazine." ]

[ "nan" ]

[ "1102976", "9241405", "3426836", "6637861" ]

[ "Termination of restricted diet in children with phenylketonuria: a randomized controlled study.", "Transitory hyperphenylalaninaemia in children with continuously treated phenylketonuria.", "Neuropsychological studies on adolescents with phenylketonuria returned to phenylalanine-restricted diets.", "Phenylalanine intakes of 1- to 6-year-old children with phenylketonuria undergoing therapy." ]

[ "This study demonstrates the feasibility of a randomized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria. The parents of 14 of 16 children gave informed consent, knowing their children would be randomly assigned to either a diet-continuation or a diet-termination group. Compared with the continuation group, the mean serum phenylalanine of the termination group was 15.1 mg per dl higher (P less than 0.005) one year, and 9.2 mg per dl higher (P less than 0.025) two years after diet termination. Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group (P less than 0.01). There were no significant differences in mean head circumferences, height or performances on psychologic tests. At age six, mean I.Q. in the terminated group was 99.8, in those continuing the diet 103.6. Children in both groups showed some subtest scatter in memory and concentration. Thus, no harmful effects of diet termination were noted, but a longer period of observation in a larger number of subjects is needed.", "Cognitive and behavioral effects of temporarily challenging the CNS with elevated levels of phenylalanine in treated phenylketonuria (PKU) were investigated in a triple-blind, cross-over study. A high phenylalanine supplement was given over 3 months to sixteen 10- to 16-year-old early and continuously treated children with classical PKU. We used the WISC and Rivermead tests to measure cognitive function and the Rutter Scales to assess disordered behavior. Parents and children guessed at the condition imposed. The Group x Phase interaction for phenylalanine level was statistically significant, but this pattern was not mirrored in the psychological test data, and guessing was random. Results suggest that intellectual ability, memory, and conduct are not affected by medium-term hyperphenylalaninaemia in PKU after 10 or more years of treatment.", "Nine adolescents with phenylketonuria (PKU), who had been on unrestricted diets for 2 to 11 years, underwent serial neuropsychological testing over two consecutive 4- to 5-week periods during which each was maintained on a low-phe diet supplemented in a triple-blind fashion either with L-phe (high phe) or L-alanine (low phe). Assignment to the initial condition was done randomly, and the alternate condition was substituted at the end of the first 4- to 5-week period. In 6 of 7 subjects with PKU, baseline median choice reaction times (RTs) were slower than those of controls matched for age, sex, handedness, and Full-Scale IQ (WISC-R). A highly significant improvement occurred during the low-phe phases of the study. Results suggest that adolescents with PKU on unrestricted diets have a neuropsychological deficit that is out of proportion to their overall intellectual handicap. Moreover, this deficit appears to be at least partly reversible by return to dietary phe restriction despite years of hyperphenylalaninemia.", "Mean of median phenylalanine intakes of 1- to 6-yr-old treated phenylketonuria patients who were growing normally were evaluated by age, sex, and treatment group assignment. Total daily means of median phenylalanine intakes of subjects in treatment group 1 were significantly different from those of subjects in treatment group 2 except at the median age of 69 months. Total daily phenylalanine intakes varied from 285 +/- 10 to 453 +/- 30 mg (mean +/- SEM) by subjects in treatment group 1. Total daily phenylalanine intakes of subjects in treatment group 2 varied from 349 +/- 12 to 530 +/- 42 mg (mean +/- SEM). Mean, median phenylalanine intakes by males ranged from 30 mg/kg of body weight by the younger to 23 mg/kg of body weight by the older subjects. Means of median phenylalanine intakes of females varied from 32 mg/kg of body weight by the younger to 21 mg/kg of body weight by the older subjects. No child had a median phenylalanine intake below 10 mg/kg of body weight." ]

[ "16319303" ]

[ "Donepezil in the prevention and treatment of post-surgical delirium." ]

[ "Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery.\n A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant.\n Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility.\n This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population." ]

[ "11409130", "18482350", "17650168" ]

[ "Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial.", "Diclofenac sodium and occlusal splint therapy in TMJ osteoarthritis: a randomized controlled trial.", "Osteoarthritis of the temporomandibular joint: an evaluation of the effects and complications of corticosteroid injection compared with injection with sodium hyaluronate." ]

[ "To compare the treatment potential of glucosamine sulfate (GS) and ibuprofen in patients diagnosed with temporomandibular joint (TMJ) osteoarthritis (OA).\n Forty women and 5 men received either GS (500 mg tid) or ibuprofen (400 mg tid) for 90 days in a randomized double blind study. Assessment: TMJ pain with function, pain-free, and voluntary maximum mouth opening, Brief Pain Inventory (BPI) questionnaire and masticatory muscle tenderness were performed after a one week washout and at Day 90. Acetaminophen (500 mg) dispensed for breakthrough pain was counted every 30 days to Day 120.\n In total, 176 adults were interviewed, 45 (26%) qualified, 39 (87%) completed the study (21 GS, 18 ibuprofen). Four discontinued due to stomach upset (3 ibuprofen, one GS), one due to dizziness (GS), one due to inadequate pain control (ibuprofen). Within-group analysis revealed significant improvement compared to baseline of all variables in both treatment groups but no change in acetaminophen used. Fifteen GS (71%) and 11 ibuprofen (61%) improved, with positive clinical response taken as a 20% decrease in primary outcome (TMJ pain with function). The number of patients with positive clinical response was not statistically different between groups (p = 0.73). Between-group comparison revealed that patients taking GS had a significantly greater decrease in TMJ pain with function, effect of pain, and acetaminophen used between Day 90 and 120 compared with patients taking ibuprofen.\n GS and ibuprofen reduce pain levels in patients with TMJ degenerative joint disease. In the subgroup that met the initial efficacy criteria, GS had a significantly greater influence in reducing pain produced during function and effect of pain with daily activities. GS has a carryover effect.", "The aim of the study was to compare treatment with diclofenac sodium (Voltaren 3 x 50 mg) to occlusal splint therapy in a randomized, single-blind controlled trial of patients with a diagnosis of temporomandibular joint (TMJ) osteoarthritis (OA) in accordance with Research Diagnostic Criteria for temporomandibular disorders. Patients with general joint disorders or restrictions against medication with non-steroidal anti-inflammatory drug were not included. Twenty-seven females and two males (aged 36-76 years) included, answered a standardized questionnaire and were clinically examined and they underwent TMJ tomography. The treatment was randomized to either splint (n = 15) or diclofenac (n = 14). The temperatures over the TMJs were determined. The patients were re-examined 1 week, 1 month and 3 months after the start of treatment. A 1-year follow-up was carried out using questionnaires. After 1 week of treatment with diclofenac, significant reductions of pain and discomfort, TMJ tenderness and joint pain on jaw movements were noted. The splint therapy gave a significant reduction of reported symptoms after 1 month of treatment. Both treatments gave few adverse effects and were on an equal level. Estimation of the degree of inflammation by measuring the surface temperature over the TMJ was not reliable. Structural changes of the symptomatic TMJs were radiographically found in 82%, the contralateral, symptom-free TMJ had changes in 36%. There was a discrepancy between the clinical and the radiographical findings. Diclofenac gave a more rapid improvement, but both treatments gave a significant reduction of symptoms of TMJ OA within 3 months which remained at the one-year follow-up.", "The purpose of this study was to compare the efficacy and the complications of intra-articular temporomandibular joint (TMJ) injections in 40 patients with osteoarthritis of the TMJ. The subjects were randomly divided into two groups, and the patients received either two intra-articular injections with sodium hyaluronate or two intra-articular injections with corticosteroids, 14 days apart. The effect of the treatment was evaluated 14 days, 1 and 6 months after the initial injection and was based on the following measurements: pain intensity, pain localization, joint sounds, mandibular function and complications. Both groups of patients had less pain intensity at the 6-month follow-up, and there was significantly less pain intensity in the group of patients receiving sodium hyaluronate compared with corticosteroids (P = 0.001). A decrease in crepitation was seen in both groups. In the 20 subjects receiving sodium hyaluronate both the mandibular vertical opening and protrusion increased significantly (P < 0.000). Lateral movement from the affected side increased both in subjects injected with sodium hyaluronate (P = 0.024), and those injected with corticosteroids (P = 0.042). In conclusion, this study confirms that injections in the TMJ with sodium hyaluronate or corticosteroids may reduce pain and improve function in patients with osteoarthritis. The injections were more effective in patients with only TMJ pain compared with patients suffering from both TMJ and myofascial pain. Injection with sodium hyaluronate was significantly more effective in decreasing pain intensity than corticosteroids. Temporary pain after injections may be observed." ]

[ "15342830", "2666205", "11115305", "18209205", "18977585", "18201301" ]

[ "Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial.", "Efficacy of benztropine therapy for drooling.", "Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study.", "Botulinum toxin type A for control of drooling in Asian patients with cerebral palsy.", "Treatment of sialorrhea in children with cerebral palsy: a double-blind placebo controlled trial.", "Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders." ]

[ "To investigate the clinical effectiveness of botulinum neurotoxin type A (BoNT) to reduce drooling in children with cerebral palsy (CP).\n A controlled clinical trial was performed in which the results of single-dose BoNT injections in the submandibular glands were compared with treatment with scopolamine. Forty-five children who had CP and experienced severe drooling were enrolled. Drooling severity was measured at baseline, during application of scopolamine, and at different intervals after BoNT injections up to 24 weeks, using the Drooling Quotient (DQ), the Teacher Drooling Scale (TDS), and Visual Analog Scales (VAS).\n Drooling was reduced during scopolamine application as well as after BoNT injections. Compared with baseline, the mean DQ showed a significant decrease throughout the study. Greatest reductions were achieved 2 to 8 weeks after BoNT injection. No significant differences were found between scopolamine measurements and those up to 24 months after BoNT injection. Using VAS, parents recorded the effect on drooling in which significant differences were found between baseline VAS score and all follow-up assessments. According to our definition of \"success to therapy,\" demanding a 2-point decrease on the TDS, 61.5% of patients responded to BoNT injections. Analysis of the DQ demonstrated a response rate of 53% of the patients to scopolamine and 48.7% to BoNT until 24 weeks after BoNT injections, the actual duration of this study. As a reaction to scopolamine, 71.1% of the patients had moderate to severe side effects. Only nonsevere, incidental side effects were reported after BoNT injections.\n During scopolamine application as well as after intraglandular BoNT injections, a clinically relevant reduction in drooling was achieved in children with CP, demonstrating maximum effect 2 to 8 weeks after injections. This is the first controlled clinical trial that confirmed a significant effect of BoNT injections in the treatment of drooling. General anesthesia was needed for all children. BoNT injections show fewer and less serious side effects than transdermal scopolamine treatment.", "This study assessed the efficacy of synthetic anticholinergic benztropine and incidence of side-effects in 20 developmentally-disabled patients with severe drooling. The double-blind, placebo-controlled, crossover protocol included one-week baseline, two-week placebo and two-week benztropine conditions (mean dose 3.8 mg). A significant decrease in drooling during the benztropine condition relative to placebo was demonstrated and conservative response rates (calculated by deleting placebo responders), ranged up to 65 to 70 per cent. For patients completing the protocol the incidence of side-effects did not differ across conditions and minor problems such as a dry mouth were eliminated by small dose adjustments. More serious cholinergic side-effects, which resolved within 24 to 48 hours, necessitated discontinuation of the drug in three patients. This study demonstrates that synthetic anticholinergics can provide an important therapeutic alternative to surgical and behavioral therapies for drooling.", "To determine the safety and efficacy of glycopyrrolate in the treatment of developmentally disabled children with sialorrhea.\n Placebo-controlled, double-blind, crossover dose-ranging study.\n Outpatient facilities in 2 pediatric hospitals.\n Thirty-nine children with both developmental disabilities and excessive and bothersome sialorrhea.\n Parent and investigator evaluation of change in sialorrhea and adverse effects.\n Glycopyrrolate in doses of 0.10 mg/kg per dose is effective at controlling sialorrhea. Even at low doses, 20% of children may exhibit adverse effects severe enough to require discontinuation.\n Glycopyrrolate is effective in the control of excessive sialorrhea in children with developmental disabilities. Approximately 20% of children given glycopyrrolate may experience substantial adverse effects, enough to require discontinuation of medication. Arch Pediatr Adolesc Med. 2000;154:1214-1218.", "nan", "To prospectively study the efficacy and safety of intraparotid gland injection of Botulinum neurotoxin serotype A (Dysport) for the treatment of sialorrhea (drooling) in children with cerebral palsy (CP).\n Twenty-four children, ages 21 months to 7 years, were recruited and randomized to receive either treatment with 100U Botulinum toxin or placebo. Rating scales for the frequency and severity of drooling were performed at the time of injection, at 1 month, and at baseline prior to the second injection. A second set of injections of either 140U of drug or placebo was given 4 months later, and the same rating scales were used. Eight patients declined the second injection. Due to high dropouts in the placebo group in second set of injections, statistical analysis was performed for the results of the initial injection only.\n Scores of the median frequency (p=0.034) and severity (p=0.026) of drooling were reduced in the treatment group. Median total score also declined in the treatment group (p=0.027). After the second injection, five out of nine patients injected with the drug showed a decline in the total score; including three patients who did not respond to the first injection. Only two patients experienced transient increase in drooling after the treatment with the drug.\n Botulinum toxin is an effective and safe treatment option for drooling in children with CP.", "The primary aim of this randomized, controlled trial was to assess the effectiveness of botulinum toxin A (BoNT-A) injections into the submandibular and parotid glands on drooling in children with cerebral palsy (CP) and other neurological disorders. Secondary aims were to ascertain the duration of any such effect and the timing of maximal response. Of the 48 participants (27 males, 21 females; mean age 11y 4mo [SD 3y 3mo], range 6-18y), 31 had a diagnosis of CP and 15 had a primary intellectual disability; 27 children were non-ambulant. Twenty-four children randomized to the treatment group received 25 units of BoNT-A into each parotid and submandibular gland. Those randomized to the control group received no treatment. The degree and impact of drooling was assessed by carers using the Drooling Impact Scale questionnaire at baseline and at monthly intervals up to 6 months postinjection/baseline, and again at 1 year. Maximal response was at 1 month at which time there was a highly significant difference in the mean scores between the groups. This difference remained statistically significant at 6 months. Four children failed to respond to the injections, four had mediocre results, and 16 had good results. While the use of BoNT-A can help to manage drooling in many children with neurological disorders, further research is needed to fully understand the range of responses." ]

[ "8556969", "7065831", "10716102", "1311974", "15876901", "1968773", "7869468", "8957147", "3977557", "4028630", "22540433", "22137413", "12095666", "19686525", "6108466", "2646089", "12633912", "12237786" ]

[ "Craving and drug reward: a comparison of methadone and clonidine in detoxifying opiate addicts.", "Withdrawal from heroin in three or six weeks. Comparison of methadyl acetate and methadone.", "Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance.", "Assessment and management of opioid withdrawal symptoms in buprenorphine-dependent subjects.", "Efficacy of buspirone in the treatment of opioid withdrawal.", "Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial.", "Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients.", "Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal.", "Clonidine in outpatient detoxification from methadone maintenance.", "Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin.", "Tramadol versus methadone for treatment of opiate withdrawal: a double-blind, randomized, clinical trial.", "Comparison of methadone and buprenorphine for opiate detoxification (LEEDS trial): a randomised controlled trial.", "Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone.", "A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification.", "Clonidine versus methadone for opiate detoxification.", "Chlordiazepoxide vs. methadone in opiate withdrawal: a preliminary double blind trial.", "Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.", "Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone." ]

[ "Based upon findings relating to the reinstatement of responding from the animal laboratory, the present study investigated whether methadone, a synthetic opiate, would prime the desire to use heroin for its pleasant effect (i.e. for positive reinforcement) compared to clonidine, a non-opiate drug, in detoxifying opiate addicts (n = 16). In-patient opiate addicts were tested at maximum withdrawal and minimal withdrawal, and self-reported desire to use heroin (i) for its pleasant effect (positive craving) and (ii) to alleviate an unpleasant feeling or mood (negative craving) was recorded before drug administration, immediately after drug administration and on 4 further occasions, 15 min apart. In addition, self-reported rating of opiate withdrawal symptoms were also recorded. Although elevated in the methadone group, the difference between methadone and clonidine groups in positive craving did not reach statistical significance. Interpretation of the data is complicated by elevated baselines of positive craving in the methadone group at minimum withdrawal. Measures of negative craving and self-reported withdrawal symptoms showed a similar pattern of decline, and were significantly correlated at maximum withdrawal, thereby providing evidence from substance misusers themselves that the constructs of positive and negative reinforcement can be differentiated.", "A randomized clinical trial compared four methods of outpatient withdrawal from heroin. Sixty-one subjects were assigned in a double-blind manner to treatment with either methadone or methadyl acetate. Within each drug group, subjects were assigned to detoxification programs either within the standard three-week period or in an extended six weeks of treatment. Outcome measures included retention to the end of the dosing schedule, use of illicit drugs during treatment, subjective discomfort, satisfaction, staff ratings of global progress, and durability of change at a three-month follow-up. Methadyl acetate performed similarly to methadone in most respects. Six-week withdrawal showed some temporary benefits over standard treatment, but these advantages should be weighed against the greater cost of the longer treatment and similarity of follow-up outcome.", "A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients.", "The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic.", "In an attempt to develop a new opiate detoxification approach, the authors assessed the efficacy of buspirone in the treatment of acute heroin withdrawal. Buspirone, a drug interacting with the serotonergic system, was selected because there is evidence that a decrease in serotonergic neurotransmission may be involved in opiate withdrawal symptoms. Twenty-nine hospitalized heroin addicts were randomized to 4 groups: (1) placebo; (2) methadone; (3) buspirone 30 mg daily; (4) buspirone 45 mg daily. The double-blind trial started in all patients with a 5-day methadone stabilization period ending with a 30-mg dose. This was followed from days 6 through 12 by placebo in group 1 and by a methadone taper in group 2. Because of its delayed action, buspirone was started on day 1 in groups 3 and 4 and was continued, after methadone discontinuation, through day 12. On day 13, drugs and placebo were discontinued and patients were observed through day 14. Withdrawal symptoms were assessed with the \"Subjective Opiate Withdrawal Scale\" (SOWS) and the \"Objective Opiate Withdrawal Scale\" (OOWS). The SOWS and OOWS scores were significantly higher in the placebo group than in the methadone, buspirone 30 mg, and buspirone 45 mg groups. There were no significant differences in SOWS or OOWS scores when the methadone group was compared with each of the two buspirone groups or when the two buspirone groups were compared with one another. In conclusion, buspirone, a nonopiate drug with no abuse potential, a safe side effect profile and no withdrawal symptoms, at doses of 30 and 45 mg, was as effective as a methadone taper in alleviating the withdrawal symptoms of heroin addicts stabilized for 5 days with, and then withdrawn from, methadone. The use of buspirone could be particularly helpful in outpatient settings where the duration of the methadone taper recommended for detoxification can be lengthy.", "The efficacy of clonidine, methadone, and guanfacine in rapid detoxification of heroin inpatients was assessed in a randomized controlled clinical trial. Signs and symptoms of abstinence and of side effects were analysed in 90 heroin addicts successfully completing a 12-day inpatient trial. All patients fit DSM-III criteria for opioid dependence, the age range being 18 to 36 years. All three drugs were effective in controlling abstinence; however, the course of abstinence was different in the methadone group as compared to the adrenergic agonists, the latter showing limitations in their ability to suppress withdrawal manifestations. While mean number of withdrawal signs and symptoms was significantly lower during days 2 to 5 in the methadone group (p less than 0.01), adrenergic agonists were slightly more effective at the end of the trial. Incidence of side effects was closely related to the dose administered. Hypotensive action of adrenergic agonists was more marked in orthostatic position. The present results suggest that methadone is superior to adrenergic agonists. Between these drugs clonidine appears to be less effective than guanfacine in controlling some withdrawal manifestations, and causes more side effects, mainly of cardiovascular nature.", "In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms.", "This study compares the clinical responses to methadone and lofexidine in the treatment of opiate withdrawal in 86 polydrug-abusing opiate addicts, using a randomised double-blind study design. The lofexidine treatment more severe symptoms from day 3 to 7 and again on day 10 (the last day of treatment), but thereafter both groups showed a similar progressive symptom decline. There was no significant difference in rates of treatment completion. Both treatments had similar effects on blood pressure. Lofexidine is broadly clinically equivalent to methadone, and appears to be a non-opiate treatment of opiate withdrawal without serious limiting hypotensive side effects.", "Inpatient narcotic detoxification with clonidine hydrochloride has been used since 1978. Outpatient withdrawal, potentially more useful, has not been adequately studied. This report describes a double-blind random assignment of 49 methadone hydrochloride-maintained patients whose dose had been lowered to 20 mg. Twenty-five were detoxified using methadone at 1-mg decrements, 24 by abrupt substitution with clonidine. Approximately 40% of both groups achieved successful detoxification, with one third maintaining abstinence over the subsequent six months. The groups were also largely equivalent on withdrawal symptoms, but the clonidine group experienced symptoms in the first half of the study and the methadone group in the second half. Clonidine appears to be a safe and efficacious outpatient treatment for opiate withdrawal, although the results were less favorable than those obtained in open or inpatient studies.", "The efficacy of a rapid detoxification schedule (8 to 10 days) with clonidine or methadone was evaluated in 30 patients addicted to heroin. The dose of study drug was preestablished according to the subject's weight and the amount of opioid consumption, and the total daily dose was reduced by approximately 15% during the study. All subjects completed the detoxification program and stayed in the hospital for at least 12 days. Clonidine and methadone therapies proved to be highly effective. There was a marked reduction in anxiety during opioid detoxification, although subjects' experiences differed according to the drug used. On the day of discharge, subjects who had received methadone still had attenuated withdrawal symptoms, whereas there were no such symptoms in the clonidine group. Muscular aching, flatulence, and daily drowsiness were more common among subjects in the methadone group, while subjects in the clonidine group had more sleep disturbances and weeping. Syncopal episodes and bradycardia occurred more frequently in the clonidine group.", "The aim of this study was to compare the efficacy and safety of tramadol versus methadone for treatment of opiate withdrawal. Seventy patients randomly were assigned in two groups to receive either prescribed methadone (60 mg/day) or tramadol (600 mg/day). The withdrawal syndrome of patients was evaluated before and after rapid opiate detoxification using the Objective Opioid Withdrawal Scale (OOWS). No significant differences existed in overall OOWS scores between two groups (P = 0.11). Dropout rates were similar in both groups. Side effects in the tramadol group were as or less common than in the methadone group, with the exception of perspiration. Tramadol may be as effective as methadone in the control of withdrawal and could be considered as a potential substitute for methadone to manage opioids withdrawal.", "Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification.\n To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification.\n Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England.\n Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded.\n Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point.\n There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison.", "This paper reports results from the first controlled trial of opioid withdrawal treatment in the UK using lofexidine in a prison setting. Seventy-four opioid dependent male inmates at a Southern England prison were randomised to receive either methadone (the standard prison treatment) or lofexidine using a randomised double-blind design. No significant statistical difference between the treatment groups was found in relation to the primary variable of severity of withdrawal symptoms (effect size=0.12). No discernible difference was found in the sitting blood pressure or heart rate of the two groups during the trial. These results provide support for the use of lofexidine for the management of opioid detoxification in the prison setting.", "Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment.\n Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups.\n Three psychiatric hospitals in Austria specializing in in-patient detoxification.\n Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence.\n Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days.\n Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored.\n Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): -12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated.\n Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone.", "nan", "A double blind trial of chlordiazepoxide vs. methadone in the management of the opiate withdrawal syndrome was conducted in a group of 24 regular heroin takers. Subjective and objective measures including physiological parameters were recorded to compare the severity of opiate withdrawal between the two groups. No significant difference was found in terms of subjective withdrawal distress between the two treatment conditions, although there was a tendency to a return of withdrawal symptoms in the methadone group towards the end of treatment. A nurse rating scale demonstrated a significantly higher level of withdrawal signs in the chlordiazepoxide group on day 3. Physiological measures suggested that neither group experienced a severe withdrawal illness. A similar number in each group (37%) became completely drug free.", "With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.", "Over the last few years, there has been a growing tendency for opioid addicts to abuse multiple drugs, although many patients are in substitution therapy with methadone. Abuse of multiple drugs leads to a more complicated withdrawal syndrome; it is therefore necessary to investigate new drug strategies as a treatment for detoxification. Buprenorphine appears to be an effective and safe drug in opioid-addicted patient detoxification. In this study, we have compared the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid dependence and were included in this study. All patients abused various additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non-completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine, but the difference in the dropout rate was not significant. However, patients with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms after the first two weeks of treatment. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than methadone/carbamazepine in detoxification strategies for opioid addict with additional multiple drug abuse. No severe side effects occurred during treatment in either group." ]

[ "12199836", "3580094", "9231446", "8659651" ]

[ "Operation safe crossing: using science within a community intervention.", "Deterring the drinking driver: the Stockton experience.", "The effect of drinking and driving interventions on alcohol-involved traffic crashes within a comprehensive community trial.", "Reducing alcohol-impaired driving in Massachusetts: the Saving Lives Program." ]

[ "To evaluate a large drunk-driving enforcement program at the US/Mexican border to reduce the number of youths crossing the border to drink in Tijuana. This paper also describes the research data used to develop and manage the program. Data from a border breath-test survey were used to dramatize the problem and gain public support for action. The data were also used to help design the enforcement effort and measure progress in reducing the cross-border drinking problem.\n The number of news events generated around the occurrence of special enforcement efforts were used to measure project activity and to predict changes in the numbers of youths crossing into Mexico, their returning BACs and reductions in alcohol-related crashes during a 3-year period.\n An urban county on the Mexican border.\n Underage youths aged 18-20 years and young adults aged 21-30 years residing in San Diego County.\n Immigration and Naturalization Services provided population counts of the number of individuals crossing each weekend night from Tijuana into the United States through the San Ysidro border facility. Breath-test surveys of a random sample of these returning crossers provided data on the number of US residents visiting bars and nightclubs in Tijuana and on alcohol consumption at Tijuana bars and nightclubs. Night-time had-been-drinking crash data involving young drivers in several California counties served as an outcome measure of public health and safety.\n Analysis of data involving more than 2 million pedestrians returning from Tijuana indicated that the Operation Safe Crossing program reduced the number of late-night crossers by 31.6%.\n Effective use of data through media advocacy programs to support an enforcement effort can reduce alcohol-related crashes.", "The effectiveness of drunk driving enforcement patrols is generally assumed. However, few adequate evaluations are available in the traffic safety literature. The U.S. Department of Transportation funded a special program in Stockton, a city with a population of 120,000 in the central valley of California, to test the effectiveness of special drunk driving patrols on weekend evenings, applied within a setting in which no other major alcohol safety programs were present. The objective of this effort was to determine the effectiveness of a \"traditional\" approach to enforcing driving while impaired (DWI) laws; one in which innovative procedures such as sobriety checkpoints were not used. The results indicated that nighttime collisions in Stockton were reduced during the three and a half year period of the special enforcement program.", "The Drinking and Driving Component, one of five elements of the Community Trials Project, involved the implementation of a special drink driving countermeasure in the three experimental communities, one in Northern California, one in Southern California and another in South Carolina. This intensified enforcement of driving under the influence (DUI) was designed to deter potential drinking drivers by increasing their perception of the risk of being arrested leading to a reduction in the consumption of alcohol before driving. See component detailed description in Voas (1997, this issue). The evaluation found that media advocacy training and technical assistance resulted in increased DUI news coverage and that additional police officer hours for DUI enforcement, greater use of breathalyzer equipment, increased officer training and more checkpoints produced increased DUI enforcement. The combined effects of increased DUI news coverage and DUI enforcement yielded increased public perceived risk of arrest and subsequently less drinking and driving. Overall the evaluation found that alcohol-involved traffic crashes were reduced as a result of this component in the experimental communities as contrasted with the matched comparison communities.", "The purpose of this study ws to assess whether a community program begun in March 1988 that organized multiple city departments and private citizens could reduce alcohol-impaired driving, related driving risks, and traffic deaths and injuries.\n Trends in fatal crashes and injuries per 100 crashes were compared in Saving Lives Program cities and the rest of Massachusetts from March 1984 through February 1993. In annual roadside surveys conducted at randomly selected locations, safety belt use among occupants of 54577 vehicles and travel speeds of 118442 vehicles were observed. Four statewide telephone surveys (n = 15188) monitored self-reported driving after drinking.\n In program cities relative to the rest of Massachusetts during the 5 program years in comparison with the previous 5 years, fatal crashes declined 25%, from 178 to 120, and fatal crashes involving alcohol decreased 42%, from 69 to 36. Visible injuries per 100 crashes declined 5%, from 21.1 to 16.6. The proportions of vehicles observed speeding and teenagers who drove after drinking were cut in half.\n Interventions organized by multiple city departments and private citizens can reduce driving after drinking, related driving risks, and traffic deaths and injuries." ]

[ "16509906", "8267099", "8560322", "8832113", "10798837", "15232022", "15291706", "10925764", "16600372", "9919639", "14524428", "15981131", "15608548", "15245678", "19719026" ]

[ "Mental health of children in foster and kinship care in New South Wales, Australia.", "Child maltreatment in family foster care.", "Pathways of older adolescents out of foster care: implications for independent living services.", "The reported health and functioning of children maltreated while in family foster care.", "Children in foster care: factors influencing outpatient mental health service use.", "Use of mental health services among older youths in foster care.", "Children's voices: the perceptions of children in foster care.", "Understanding reentry to out-of-home care for reunified infants.", "Who disrupts from placement in foster and kinship care?", "Satisfaction of children in out-of-home care.", "Building evidence to promote educational competence of youth in foster care.", "A comparison of mental health problems in kinship and nonkinship foster care.", "Prevalence of psychiatric disorders among older youths in the foster care system.", "Challenging children in kin versus nonkin foster care: perceived costs and benefits to caregivers.", "Prevention and drug treatment." ]

[ "To report baseline mental health measures from the Children in Care study, a prospective epidemiological study of children in court-ordered foster and kinship care in New South Wales, Australia.\n Mental health, socialization and self-esteem were assessed in 347 children in a statewide mail survey, using two carer-report checklists, the Child Behavior Checklist (CBCL) and the Assessment Checklist for Children (ACC).\n Children in the study had exceptionally poor mental health and socialization, both in absolute terms, and relative to normative and in-care samples. Levels and rates of disturbance for children in foster care exceeded all prior estimates. Rates of disturbance for children in kinship care were high, but within the range of prior estimates. Boys presented with higher scope and severity of mental health problems than girls on the CBCL, while gender-specific patterns of disturbance were shown on the ACC. A moderate age effect was accounted for by children's age at entry into care.\n Children in care are at high risk of mental health problems. Psychological support for the children and their carers is an essential secondary prevention strategy. Implications for service delivery are discussed.", "Predictors of maltreatment of children living in family foster care were sought in characteristics of foster homes. Four characteristics that presented increased risk were identified: homes that had younger foster mothers, homes in which children shared bedrooms with other family members, homes about which case-workers had reservations, and homes that were restricted for placement of certain children. Kinship-care homes were found to present decreased risk.", "This article reports the results of a study of final discharge outcomes for an exit cohort of 2,653 foster youths in California who were at least 17 years old at exit and had spent at least 18 months in care before their final discharge. A logistic regression model of discharge status was developed that expresses the effect of selected variables on the odds that a child exited foster care via one of three routes: (1) by reaching the age of majority while still in care or being legally emancipated to independent living; (2) by family reunification, placement with a relative or guardian, or adoption; or (3) by an \"unsuccessful\" exit from care. A youth's number of placements in foster care, time spent in care, and the type of placement the child last resided in were all found to be related to final discharge status. The implications of these findings for efforts to prepare foster youths for independent living are discussed. Of particular interest is the finding that a large proportion of youths who have spent a long time in foster care away from their families nevertheless return to their families at exit from care.", "The ability to assess accurately risk factors for maltreatment while in family foster care is essential for developing prevention and intervention strategies. Yet information about children involved in maltreatment episodes while in foster care is severely limited. This correlational study reports on characteristics, health, and functioning parameters of all 78 children with substantiated maltreatment reports between 1984-1988 in an urban foster care program as compared to a random sample of 229 nonmaltreated children in foster care in the same time period. Almost 50% of the substantiated maltreatment was sexual abuse with the remainder physical abuse and neglect. Problems in health, development, and functioning were reported in the social services record for a large number of all children, but children sexually abused while in care were significantly more likely to have a nonkinship placement, and to have mental health and development problems identified. Physical abuse and neglect while in foster care were not associated with child health and functioning characteristics. The implications of these results are discussed within the context of the data source used.", "To determine factors influencing outpatient mental health service use by children in foster care.\n Detailed survey and administrative data were collected on 480 children who entered long-term foster care in San Diego County from May 1990 through October 1991. These data were linked with claims data from Medicaid and San Diego County Mental Health Services information systems. A Poisson regression model was used to determine whether the following factors influenced outpatient mental health service use: age, race/ethnicity, gender, maltreatment history, placement pattern, and behavioral problems as measured by the Achenbach Child Behavior Checklist (CBCL).\n Except for maltreatment history, all independent variables included in the multivariate regression model were statistically significant. The total number of outpatient mental health visits increased with age, male gender, and non-relative foster placements. Relative to Caucasians, visits were lower for Latinos, and Asian/Others, but comparable for African-Americans. Concerning maltreatment history, differences were only found in one category; children experiencing caretaker absence received fewer visits compared to children who did not experience caretaker absence. Children with CBCL Total Problem Scale T-scores of 60 or greater had significantly more visits than those with a score less than 60.\n Both clinical and non-clinical factors influence outpatient mental health service use by foster children. Limitations imposed by gender, race/ethnicity, and placement setting need to be addressed by child welfare policies. These finding suggest that guidelines are needed to systematically link children in foster care with behavioral problems to appropriate services.", "This study examined lifetime, 12-month, and current mental health service use among older youths in the foster care system and examined variations in mental health care by race, gender, maltreatment history, living situation, and geographic region.\n The Service Assessment for Children and Adolescents, the Child Trauma Questionnaire, and the Diagnostic Interview Schedule were used in interviews with 406 youths in Missouri's foster care system who were aged 17 years.\n Ninety-four percent of the youths had used a mental health service in their lifetime, 83 percent used a mental health service in the past year, and 66 percent were currently receiving a mental health service. Lifetime rates for inpatient psychiatric care (42 percent) and other residential programs (77 percent) were exceptionally high. A quarter of the youths received mental health services before they entered the foster care system. Among youths who received residential services, half did not receive community-based services before receiving residential services. After the analyses controlled for need, predisposing characteristics, and enabling characteristics, youths of color were less likely to receive outpatient therapy, psychotherapeutic medications, and inpatient services, and they were more likely to receive residential services. Youths who had been neglected and youths in kinship care were less likely to receive some types of services. Geographic differences in service use were common and sometimes mediated the effect of race on service use.\n The child welfare system was actively engaged in arranging mental health services for youths in the foster care system, but the system was unable to maintain many youths in less restrictive living situations. The variations by race and geography indirectly indicate quality concerns.", "Scant research exists on how abused and neglected children view the foster care experience and how these perceptions vary by demographic characteristics and placement type. Data come from a national probability sample of children placed in child welfare supervised foster care for at least 1 year. These findings indicate that children generally feel positively toward their out-of-home care providers and maintain hope for reunification with their biological family. Differences are present between children in family foster care, group care, and kinship care placements.", "Although many children placed in out-of-home care are reunified with their families of origin, a significant portion reenter care, reflecting continued family problems and weaknesses within the child welfare system. For infants, the stability of reunification is particularly crucial, given their developmental stage. This study reviewed the case records of 88 randomly selected infants who had been reunified with their families. Thirty-two percent of those infants reentered care within four to six years of their reunification. The identification of factors predictive of reentry into care has both policy and practice implications.", "To identify reliable, inexpensive predictors of foster care placement disruption that could be used to assess risk of placement failure.\n Using the Parent Daily Report Checklist (PDR), foster or kinship parents of 246 children (5-12 years old) in California were interviewed three times about whether or not their foster child engaged in any of the 30 problem behaviors during the previous 24 h. PDR was conducted during telephone contacts (5-10 min each) that occurred from 1 to 3 days apart at baseline. Disruptions were tracked for the subsequent 12 months. Other potential predictors of disruption were examined, including the child's age, gender, and ethnicity, the foster parent's ethnicity, the number of other children in the foster home, and the type of placement (kin or non-kin).\n Foster/kin parents reported an average of 5.77 child problems per day on the PDR checklist. The number of problem behaviors was linearly related to the child's risk of placement disruption during the subsequent year. The threshold for the number of problem behaviors per day that foster and kinship parents tolerated without increased risk of placement disruption for these latency-aged children was 6 or fewer. Children in non-kin placements were more likely to disrupt than those in kinship placements. There was a trend for increased risk of disruption as the number of children in the home increased.\n The PDR Checklist may be useful in predicting which placements are at most risk of future disruption, allowing for targeted services and supports.", "A randomly selected sample of 1,100 children in out-of-home care in Illinois from 1993 to 1996 were interviewed in person regarding their satisfaction with the homes in which they lived and with their caregivers. They were also asked whether they felt loved and safe, and rated the quality of their lives before and after placement into care. The children rated their satisfaction with their living arrangements and with their caregivers as high, especially those who had lived in family foster care.", "Although the academic difficulties of students living in foster care are well documented, few studies have examined factors influencing academic achievement of youth in foster care. This article reports the results of a study of educational competence in a sample of 152 foster youth in one midwestern state. Using five standardized instruments, the study explored predictors of reading ability of youth in foster care. Multiple regression analyses indicated that four factors--aspiration for higher education, placement in kinship care, participation in extracurricular activities, and drug use--accounted for 39% of the variance in reading ability scores. The article discusses implications of these findings for practice, research, and policy development.", "Knowledge of the emotional and behavioural problems of children in kinship foster care is scarce. No data on such problems in European countries have been published. This study compares child psychiatric problems and placement characteristics of children living in kinship and nonkinship foster care.\n A total of 214 children in kinship and nonkinship foster care, aged 4-13, participated in the study. The Child Behavioral Checklist (CBCL) was completed by their foster parents and demography and placement information was collected.\n Of the nonkinship group, 51.8 % scored above the borderline on the CBCL Total Problem score, as did 35.8% of the kinship group. The kinship group had fewer previous placements, were more often fostered within their local community and had more contact with their biological parents. Kinship foster parents had lower social status, in terms of educational level. Variables significantly related to high level of the CBCL Total problems score were male gender and location of foster home outside community of birth family. Positive outcome was significantly associated with placement within the child's own community, which in turn was related to kinship placement.\n Placement in kinship foster care should be considered as a viable possibility.", "To estimate the lifetime and past year prevalence rates of major psychiatric disorders in a sample of older youths in the foster care system, to examine the timing of disorder onset and system entry, and to explore variations in past year prevalence rates.\n Using the Diagnostic Interview Schedule for DSM-IV, interviews were conducted with 373 17-year-old youths (90% of those eligible) in one state's foster care system between December 2001 and June 2003.\n : Sixty-one percent of the youths qualified as having at least one psychiatric disorder during their lifetime; of these youths, 62% reported onset of their earliest disorder before entering the foster care system. In addition, 37% of youths met criteria for a psychiatric disorder in the past year. The number of types of maltreatment experienced was the most robust predictor of psychiatric disorder among several maltreatment variables. There were no differences in prevalence rates for youths in kinship care and those in nonkin foster families.\n Older youths in the foster care system have disproportionately high rates of lifetime and past year psychiatric disorders. Results support recommendations for initial and periodic mental health assessments for these youths and mechanisms to continue mental health services for young adults transitioning out of the foster care system.", "This study uses social exchange theory as a framework for examining 102 kin and 157 nonkin foster parents' perceptions of their foster children, their relationships with them, and their own functioning. The authors argue that these perceptions reflect perceived costs and benefits of parenting these children, which may influence their investment in them. All children in the study were referred to Parent-Child Interaction Therapy (PCIT) for treatment of the children's behavior problems, participating with their foster parents. Analyses showed that nonkin caregivers rated their foster children's behavior problems as significantly more severe than kin caregivers but rated themselves as significantly less stressed. Analyses predicting early treatment termination showed that kin caregivers were more likely than nonkin caregivers to complete the course of treatment in PCIT, particularly if they reported elevated levels of parental distress. The authors discuss the implications of these findings for foster children's placement stability and long-term success.", "Evidence linking alcohol and other drug abuse with child maltreatment, particularly neglect, is strong. But does substance abuse cause maltreatment? According to Mark Testa and Brenda Smith, such co-occurring risk factors as parental depression, social isolation, homelessness, or domestic violence may be more directly responsible than substance abuse itself for maltreatment. Interventions to prevent substance abuse-related maltreatment, say the authors, must attend to the underlying direct causes of both. Research on whether prevention programs reduce drug abuse or help parents control substance use and improve their parenting has had mixed results, at best. The evidence raises questions generally about the effectiveness of substance abuse services in preventing child maltreatment. Such services, for example, raise only marginally the rates at which parents are reunified with children who have been placed in foster care. The primary reason for the mixed findings, say Testa and Smith, is that almost all the parents face not only substance abuse problems but the co-occurring issues as well. To prevent recurring maltreatment and promote reunification, programs must ensure client progress in all problem areas. At some point in the intervention process, say Testa and Smith, attention must turn to the child's permanency needs and well-being. The best evidence to date suggests that substance-abusing parents pose no greater risk to their children than do parents of other children taken into child protective custody. It may be sensible, say the authors, to set a six-month timetable for parents to engage in treatment and allow twelve to eighteen months for them to show sufficient progress in all identified problem areas. After that, permanency plans should be expedited to place the child with a relative caregiver or in an adoptive home. Investing in parental recovery from substance abuse and dependence, the authors conclude, should not substitute for a comprehensive approach that addresses the multiple social and economic risks to child well-being beyond the harms associated with parental substance abuse." ]

[ "10592853" ]

[ "A comparative study of the safety and efficacy of FemCap, a new vaginal barrier contraceptive, and the Ortho All-Flex diaphragm. The FemCap Investigators' Group." ]

[ "The FemCap is a new silicone rubber barrier contraceptive shaped like a sailor's hat, with a dome that covers the cervix, a rim that fits into the fornices, and a brim that conforms to the vaginal walls around the cervix. It was designed to result in fewer dislodgments and less pressure on the urethra than the cervical cap and diaphragm, respectively, and to require less clinician time for fitting. This was a phase II/III, multicenter, randomized, open-label, parallel group study of 841 women at risk for pregnancy. A subset of 42 women at one site underwent colposcopy. Women were randomized to use the FemCap or Ortho All-Flex contraceptive diaphragm, both with 2% nonoxynol-9 spermicide, for 28 weeks. The objectives were to compare the two devices with regard to their safety and acceptability and to determine whether the probability of pregnancy among FemCap users was no worse than that of the diaphragm (meaning not more than 6 percentage points higher). The 6-month Kaplan-Meier cumulative unadjusted typical use pregnancy probabilities were 13.5% among FemCap users and 7.9% among diaphragm users. The adjusted risk of pregnancy among FemCap users was 1.96 times that among diaphragm users, with an upper 95% confidence limit of 3.01. Clinical equivalence (noninferiority) of the FemCap compared with the diaphragm, as defined in this study, would mean that the true risk of pregnancy among FemCap users was no more than 1.73 times the pregnancy risk of diaphragm users. Because the observed upper 95% confidence limit (and even the point estimate) exceeded 1.73, the probability of pregnancy among FemCap users, compared with that among diaphragm users, did not meet the definition of clinical equivalence used in this study. The FemCap was believed to be safe and was associated with significantly fewer urinary tract infections. More women reported problems with the FemCap with regard to insertion, dislodgement, and especially removal, although their general assessments were positive. The two devices were comparable with regard to safety and acceptability, but a 6-point difference in the true 6-month pregnancy probabilities of the two devices could not be ruled out. Further studies are needed to determine whether design modifications can simplify insertion and removal." ]

[ "10641772", "8291819", "10786491" ]

[ "A prospective, randomized multicenter study comparing APD and CAPD treatment.", "Clinical efficacy and morbidity associated with continuous cyclic compared with continuous ambulatory peritoneal dialysis.", "Comparative evaluation of CAPD and PD-plus effectiveness." ]

[ "The goals for maintenance dialysis treatment are to improve patient survival, reduce patient morbidity, and improve patient quality of life. This is the first randomized prospective study comparing automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) treatment with respect to quality of life and clinical outcomes in relation to therapy costs.\n A prospective, randomized multicenter study.\n Three Danish CAPD units.\n Thirty-four adequately dialyzed patients with high or high-average peritoneal transport characteristics were included in the study.Twenty-five patients completed the study.\n After randomization, 17 patients were allocated to APD treatment and 17 patients to CAPD treatment for a period of 6 months. Medical and biochemical parameters were evaluated at monthly controls in the CAPD units. Quality-of-life parameters were assessed at baseline and after 6 months by the self-administered short-form SF-36 generic health survey questionnaire supplemented with disease- and treatment-specific questions. Therapy costs were compared by evaluating dialysis-related expenses.\n Quality-of-life parameters, dialysis-related complications, dialysis-related expenses.\n The quality-of-life studies showed that significantly more time for work, family, and social activities was available to patients on APD compared to those on CAPD (p < 0.001). Although the difference was not significant, there was a tendency for less physical and emotional discomfort caused by dialysis fluid in the APD group. Sleep problems, on the other hand, tended to be more marked in the APD group. Any positive effect of APD compared to CAPD on dialysis-related hospital days or complication rates could not be confirmed. With larger patient samples, it is possible, however, that a significant difference might have been achieved. The running costs for APD treatment were US $75 per day and for CAPD treatment US $61 per day.\n If APD treatment can help to keep selected patients vocationally or socially active, paying the extra cost seems reasonable.", "To assess the clinical efficacy and morbidity of continuous cyclic peritoneal dialysis compared with continuous ambulatory peritoneal dialysis with a Y-connector as renal replacement therapy.\n Prospective, randomized study.\n University hospital.\n All new patients with end-stage renal failure consecutively entering the dialysis program from January 1988 through July 1991 were randomly assigned to receive continuous ambulatory peritoneal dialysis with a Y-connector or continuous cyclic peritoneal dialysis and were followed prospectively.\n Patient and technique survival, dialysis adequacy, and (infectious) morbidity.\n Forty-one patients (median age, 56 years; range, 18 to 86 years) started continuous ambulatory peritoneal dialysis with a Y-connector (follow-up, 688 patient-months), and 41 patients (median age, 54 years; range 21 to 76 years) started continuous cyclic peritoneal dialysis (follow-up, 723 patient-months). The two groups showed no significant differences in adequacy of dialysis (as assessed by blood pressure control and laboratory and neurologic variables) and patient or technique survival. Renal transplant was the primary reason for discontinuing the assigned dialysis technique in both groups. The average number of hospitalizations per patient-year was 1.0 using continuous ambulatory peritoneal dialysis with a Y-connector and 0.6 per patient-year using continuous cyclic peritoneal dialysis (P = 0.02), with a mean duration of 10.8 and 9.6 days per admission, respectively (not significant). Peritonitis occurred significantly less often in those receiving continuous cyclic peritoneal dialysis (0.94 compared with 0.51 episodes per patient-year; P = 0.03). No difference in causative pathogens was observed. Exit site infection rate was 0.38 episodes per patient-year in both groups.\n In an unselected patient group, continuous cyclic peritoneal dialysis was accompanied by significantly lower rates of peritonitis and dialysis-related hospital admission, whereas it was as effective as continuous ambulatory peritoneal dialysis with a Y-connector for patient and technique survival.", "Decline in residual renal function in CAPD patients often leads to reduced overall solute clearances. Inadequate dialysis has been linked to malnutrition and increased morbidity and mortality rates. Achieving dialysis adequacy targets is often difficult by the conventional method of increasing CAPD exchange volumes. In comparison, substantial increases in solute clearances can be achieved with the use of automated peritoneal dialysis with large fill volumes and an extra daytime exchange." ]

[ "10485679", "12578443", "14769785", "2181158", "15995051", "3683478", "8320510", "6778335", "7002375", "19819563", "2196954", "15126745", "2872514", "646300" ]

[ "Adenoidectomy and adenotonsillectomy for recurrent acute otitis media: parallel randomized clinical trials in children not previously treated with tympanostomy tubes.", "Prevention of otitis media by adenoidectomy in children younger than 2 years.", "Adenoidectomy versus chemoprophylaxis and placebo for recurrent acute otitis media in children aged under 2 years: randomised controlled trial.", "Efficacy of adenoidectomy for recurrent otitis media in children previously treated with tympanostomy-tube placement. Results of parallel randomized and nonrandomized trials.", "Adenoidectomy does not significantly reduce the incidence of otitis media in conjunction with the insertion of tympanostomy tubes in children who are younger than 4 years: a randomized trial.", "Effectiveness of adenoidectomy and tympanostomy tubes in the treatment of chronic otitis media with effusion.", "A randomized study of the surgical management of children with persistent otitis media with effusion associated with a hearing impairment.", "Adenoidectomy for otitis media with mucoid effusion.", "Adenoidectomy for middle ear disorders: a randomized controlled trial.", "Adenoidectomy for otitis media with effusion in 2-3-year-old children.", "A randomised controlled trial of surgery for glue ear.", "Adenoidectomy: selection criteria for surgical cases of otitis media.", "Otoscopic, impedance, and audiometric findings in glue ear treated by adenoidectomy and tonsillectomy. A prospective randomised study.", "Effects of adenoidectomy: a controlled two-year follow-up." ]

[ "Adenoidectomy and adenotonsillectomy are commonly performed in US children to reduce the occurrence of persistent or recurrent otitis media, but evidence supporting the efficacy of the operations is limited.\n To test the efficacy of adenoidectomy and adenotonsillectomy in children with persistent or recurrent otitis media who had not previously undergone tube placement and to compare the relative efficacy of adenoidectomy alone vs adenotonsillectomy in such children.\n Two parallel randomized clinical trials.\n A total of 461 children aged 3 to 15 years were enrolled at Children's Hospital of Pittsburgh, Pa, between April 1980 and April 1994. Four hundred ten children were observed for up to 3 years.\n Children without recurrent throat infection or tonsillar hypertrophy (304 enrolled; 266 followed up) were randomized to either an adenoidectomy, adenotonsillectomy, or control group; children who had such conditions (157 enrolled; 144 followed up) were randomized to an adenotonsillectomy or control group.\n Occurrence rate of episodes of acute otitis media by treatment group and estimated proportion of time with otitis media.\n In both trials, most subjects were eligible because of recurrent acute otitis media, with or without persistent otitis media with effusion. A total of 47 children assigned to surgical treatment groups had no surgery. The efficacy of surgery in both trials was modest and limited mainly to the first follow-up year. The largest differences in that year were found in the 3-way trial between the adenotonsillectomy group and the control group: mean annual rate of episodes of acute otitis media, 1.4 vs 2.1 (P<.001); and mean estimated percentage of time with otitis media, 18.6% vs 29.9% (difference, 11.3%; 95% confidence interval, 4.4%-18.2%; P=.002). Perioperative and postoperative complications or other adverse events occurred not infrequently, especially among subjects undergoing adenotonsillectomy (14.6%).\n Our study showed limited and short-term efficacy of both adenoidectomy and adenotonsillectomy; given the risks, morbidity, and costs of these procedures, these data suggest that neither operation should ordinarily be considered as a first surgical intervention in children whose only indication is recurrent acute otitis media.", "To test the effect of adenoidectomy in connection with tympanostomy compared with tympanostomy only in preventing otitis media in children younger than 2 years.\n Prospective trial with randomized and nonrandomized arms.\n Primary care study clinics.\n The study participants were selected from 2497 children who had been enrolled in the Finnish Otitis Media Vaccine Trial at the age of 2 months. A total of 306 children, aged 1 to 2 years, who had experienced recurrent episodes of otitis media were randomized into 2 treatment groups: tympanostomy with or without adenoidectomy. Of the 306 children, 137 were operated on according to random basis (randomized trial). The 169 children whose parents declined participation in the randomized trial were operated on according to the parents' preferences (nonrandomized trial). All children were followed up until 2 years of age. The mean follow-up time was 7 months.\n The rate of acute otitis media episodes.\n The average reduction in the rate of all acute otitis media episodes in the adenoidectomy group was 19% (95% confidence interval [CI], -14% to 43%) among children enrolled in the randomized trial and 25% (95% CI, -13% to 50%) in the nonrandomized trial. The reduction in the randomized trial was mainly due to reduction in the rate of pneumococcal otitis media (58%, 95% CI, 16%-79%).\n In children younger than 2 years, concurrent adenoidectomy during the insertion of tympanostomy tubes does not seem to have a major advantage over the insertion of tympanostomy tubes alone in preventing otitis media.", "To evaluate the efficacy of adenoidectomy compared with long term chemoprophylaxis and placebo in the prevention of recurrent acute otitis media in children aged between 10 months and 2 years.\n Randomised, double blind, controlled trial.\n Oulu University Hospital, a tertiary centre in Finland.\n 180 children aged 10 months to 2 years with recurrent acute otitis media.\n Adenoidectomy, sulfafurazole (sulphisoxazole) 50 mg/kg body weight, given once a day for six months or placebo. Follow up lasted for two years, during which time all symptoms and episodes of acute otitis media were recorded.\n Intervention failure (two episodes in two months or three in six months or persistent effusion) during follow up, number of episodes of acute otitis media, number of visits to a doctor because of any infection, and antibiotic prescriptions Number of prescriptions, and days with symptoms of respiratory infection.\n Compared with placebo, interventions failed during both the first six months and the rest of the follow up period of 24 months similarly in the adenoidectomy and chemoprophylaxis groups (at six months the differences in risk were 10% (95% confidence interval -9% to 29%) and 18% (-2% to 38%), respectively). No significant differences were observed between the groups in the numbers of episodes of acute otitis media, visits to a doctor, antibiotic prescriptions, and days with symptoms of respiratory infection.\n Adenoidectomy, as the first surgical treatment of children aged 10 to 24 months with recurrent acute otitis media, is not effective in preventing further episodes. It cannot be recommended as the primary method of prophylaxis.", "We studied the efficacy of adenoidectomy in 213 children who had received tympanostomy-tube placement because of persistent and/or recurrent otitis media and had again developed otitis media after tubal extrusion. Ninety-nine of the children were assigned randomly to either an adenoidectomy group or a control group; in a separate trial, 114 children whose parents withheld consent for randomization were assigned according to parental preference. In both trials, control group outcomes appeared to have been biased favorably by the withdrawal of certain severely affected subjects from control status to receive adenoidectomy. Nonetheless, in both trials, adenoidectomy group outcomes were more favorable than control group outcomes during the first 2 follow-up years. Statistically significant differences were found mainly in the randomized trial, where during the first and second years, respectively, adenoidectomy subjects had 47% and 37% less time with otitis media than control subjects and 28% and 35% fewer suppurative (acute) episodes than control subjects. We conclude that adenoidectomy is warranted on an individualized basis for children who develop recurrent otitis media after extrusion of tympanostomy tubes.", "To evaluate the efficacy of adenoidectomy in reducing the incidence of otitis media among children who are younger than 4 years and receive tympanostomy tubes.\n A randomized trial was conducted at a tertiary center clinic. A total of 217 children who were aged 12 to 48 months and had recurrent acute otitis media (>3 episodes during the past 6 months) or chronic otitis media with effusion, no obstructive symptoms as a result of adenoid enlargement, and no previous surgical intervention were enrolled in the study. Adenoidectomy in conjunction with the insertion of tympanostomy tubes or insertion of tympanostomy tubes without adenoidectomy was studied. The number of otitis media episodes during the follow-up period of 12 months was measured.\n During the follow-up, the mean number of otitis media episodes was 1.7 among children who underwent adenoidectomy with concurrent insertion of tympanostomy tubes and 1.4 among children who received tympanostomy tubes only. The risk for recurrent otitis media (>or=3 episodes) could not be reduced by adenoidectomy (odds ratio: 1.66; 95% confidence interval: 0.80-3.46).\n Adenoidectomy does not significantly reduce the incidence of acute otitis media in otitis prone children who are younger than 4 years and receive tympanostomy tubes.", "To study the effectiveness of adenoidectomy and of the placement of tympanostomy tubes in the treatment of chronic otitis media with effusion, we randomly assigned 578 children, aged four through eight years, to receive bilateral myringotomy and no additional treatment (Group 1), placement of tympanostomy tubes (Group 2), adenoidectomy (Group 3), or adenoidectomy and placement of tympanostomy tubes (Group 4). The 491 children who underwent one of these treatments were examined at six-week intervals for up to two years. The mean time spent with effusion of any type in either ear over the two-year follow-up in the four groups was 51, 36, 31, and 27 weeks, respectively (P less than 0.0001), comparing Group 1 with each of the other groups. Hearing was equivalent in Groups 2, 3, and 4, and was significantly better than in Group 1. The most frequent sequela, purulent otorrhea, occurred one or more times in 22, 29, 11, and 24 percent of the subjects in Groups 1, 2, 3, and 4, respectively (P less than 0.001). Adenoidectomy plus bilateral myringotomy lowered the overall post-treatment morbidity (as measured by hearing acuity in the most severely affected ear [P = 0.0174] and the number of surgical retreatments required [P = 0.009]) more than did tympanostomy tubes alone and to the same degree as did adenoidectomy and tympanostomy tubes. We conclude that adenoidectomy should be considered when surgical therapy is indicated in children four to eight years old who are severely affected by chronic otitis media with effusion.", "The object of this study was to compare the effect on the hearing of the insertion of a grommet, with or without adenoidectomy, against a non-surgically managed control ear in children with persistent hearing impairment due to otitis media with effusion. Seventy-eight children (44 boys, 34 girls, mean age 5.8 years) with documented bilateral otitis media with effusion associated with a bilateral hearing impairment (pure tone average air conduction thresholds over 0.5, 1 and 2 kHz of > or = 25 dB HL) over a three month period were admitted to a randomized, controlled trial. Each child was randomized to have or not to have an adenoidectomy. The ears in each child were then randomly allocated to have a grommet (tympanostomy tube) inserted. The children's hearing status was reviewed six and 12 months post-operatively. During follow-up, should a child redevelop a persistent bilateral hearing impairment (as defined above) for three months they were managed with a hearing aid. Thus no child had repeat insertion of a grommet. Surgery of each type had an effect on the hearing and the presence of otitis media with effusion at six months post-operatively but not at 12 months when it was no different from natural resolution. If resolution of the otitis media with effusion is the outcome measure, then adenoidectomy alone is significantly better than no surgery but only in boys rather than in girls. Even in boys it only resolves about 60 per cent of effusions. However, when combined with a grommet (one insertion) adenoidectomy gives no greater resolution (89 per cent compared with 86 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)", "This random controlled study was undertaken to determine the extent to which nonsurgical treatment can control otitis media with effusion (OME); and if surgical treatment is indicated, and myringotomy, removal of middle ear liquid with insertion of aeration tubes is carried out, and whether removal of the adenoids produces any beneficial effect. A preparatory two-month nonsurgical treatment consisting of measures to improve the functional state of the nose was undertaken to eliminate from the study those children (42%) who would respond to medical treatment alone. The cure rate was similar in each of the operation groups with a greater relapse rate in the nonadenoidectomy groups who required 9% more aeration tube insertions. An estimation from x-rays of the size of the adenoids, shows that the group cured without surgery has a tendency towards the smaller adneoids. The relapse rate in the nonadenoidectomy group was independent of the size of the adenoids, and the study failed to show that any benefit accrued though adenoidectomy. Accordingly, the removal of adenoids should cease to be indicated in cases of OME as a primary form of treatment.", "Repeated tympanometric screening of a regionally defined population of 3-year-old children defined a group of 42 children with middle ear disease which had persisted for at least 6 months. These children were treated by either myringotomy with adenoidectomy or myringotomy without adenoidectomy decided by random allocation. Postoperative observation during 6 months failed to disclose any difference in middle ear status between the two groups.", "To compare the efficacy of three surgical treatment combinations - myringotomy and tympanostomy tube insertion (M&T), adenoidectomy with M&T (A-M&T), and adenoidectomy with myringotomy (A-M) - in reducing middle-ear disease in young children with chronic OME.\n Children 24-47 months of age, with a history of bilateral middle-ear effusion (MEE) for at least 3 months, unilateral for 6 months or longer or unilateral for 3 months after extrusion of a tympanostomy tube, unresponsive to recent antibiotic, were randomly assigned to either M&T, A-M&T, or A-M. Treatment assignment was stratified by age (24-35 months, 36-47 months), nasal obstruction (no, yes) and previous history of M&T (no, yes). Subjects were followed monthly and with any signs or symptoms of ear disease for up to 36 months.\n Ninety-eight subjects were randomly assigned to the three treatment groups. Fifty-six subjects (57%) were 24-35 months of age; 63% had nasal obstruction, and 36% had previously undergone M&T. During the 36 months after entry, subjects were noted to have MEE for the following percentages of time: 18.6% in the M&T group, 20.6% in the A-M&T group, and 31.1% in the A-M group (M&T vs. A-M&T, p=0.87; M&T vs. A-M, p=0.01). By 36 months, there were no differences in the number of further surgical procedures for ear disease needed among the groups.\n Adenoidectomy with or without tube insertion provided no advantage to young children with chronic OME in regard to time with effusion compared to tube insertion alone. Fewer tympanostomy tubes were placed in children undergoing A-M as their initial procedure, but this should be balanced by the performance of the more invasive surgical procedure and their increased time with effusion.", "To assess the effect of five different surgical treatments for glue ear (secretory otitis media) on improvement in hearing and, assuming one or more treatments to be effective, to identify the appropriate indications for surgery.\n Randomised controlled trial of children receiving (a) adenoidectomy, bilateral myringotomy, and insertion of a unilateral grommet; (b) adenoidectomy, unilateral myringotomy, and insertion of a unilateral grommet; (c) bilateral myringotomy and insertion of a unilateral grommet; and (d) unilateral myringotomy and insertion of a grommet. Children were followed up at seven weeks, six months, 12 months, and 24 months by symptom history and clinical investigations.\n Otolaryngology department in an urban hospital.\n 149 Children aged 4-9 years who were admitted for surgery for glue ear and who had no history of previous operations on tonsils, adenoids, or ears and no evidence of sensorineural deafness. Inadequate follow up information on levels of hearing and on middle ear function was obtained from 22.\n Mean hearing loss (dB) of the three worst heard frequencies between 250 and 4000 Hz, results of impedance tympanometry, and parental views on their child's progress.\n In the 127 children for whom adequate information was available ears in which a grommet had been inserted performed better in the short term (for at least six months) than those in which no grommet had been inserted, irrespective of any accompanying procedure. Most of the benefit had disappeared by 12 months. Adenoidectomy produced a slight improvement that was not significant, though was sustained for at least two years. The ears of children who had had an adenoidectomy with myringotomy and grommet insertion, however, continued to improve so that two years after surgery about 50% had abnormal tympanometry compared with 83% of those who had had only myringotomy and grommet insertion, and 93% of the group that had had no treatment. Logistic regression analyses identified preoperative hearing level as the single best predictor of good outcome from surgery. Other variables contributed little additional predictive power.\n If the principal objective of surgery for glue ear is to restore hearing then our study shows that insertion of grommets is the treatment of choice. The addition of an adenoidectomy will increase the likelihood of restoration of normal function of the middle ear but will not improve hearing. When deciding appropriate indications for surgery, a balance has to be made between performing unnecessary operations and failing to treat patients who might benefit from surgical intervention. Preoperative audiometry scores might be the best predictor in helping to make this decision.", "Nasopharyngeal adenoids may serve as a mechanical obstruction to the eustachian tube and contribute to the pathophysiology of otitis media (OM). The purpose of this study was to determine whether abutment of adenoids laterally against the torus tubaris affects the outcome of patients requiring pressure equalization tubes (PET) for OM.\n Randomized, controlled, prospective clinical trial.\n Patients requiring PET for recurrent acute OM or OM with persistent effusion were randomized into two groups: 1) PET placement and 2) PET placement and adenoidectomy, regardless of whether the adenoids were abutting or not abutting the torus tubaris. Patients were followed for a minimum of 1 year to determine rate of treatment failure, defined as recurrence of acute OM (>3 times/year), OM with effusion, or reinsertion of PET.\n Of the 34 patients in the abutting group, 16 patients underwent only PET insertion, of whom 8 (50%) failed, whereas 18 patients had combined PET placement and adenoidectomy, of whom 3 (17%) failed. There was a statistical difference between these two groups (P < 05). Of the 29 patients in the nonabutting group, 24 patients underwent only PET insertion, of whom 9 (37.5%) failed, whereas 5 patients underwent combined PET placement and adenoidectomy, of whom 2 (40%) failed. There was no statistical difference between these two groups (P =.92).\n This study demonstrates that the position of hypertrophied adenoids may alter the final otologic outcome of patients requiring PET insertion for OM. Patients with adenoids abutting the torus tubaris may benefit most from an adjuvant adenoidectomy.", "150 children aged between 2 and 9 years (mean 5.25 years) with chronic bilateral otitis media with effusion were randomly allocated to three groups who, in addition to unilateral myringotomy and grommet insertion, would have an adenotonsillectomy, an adenoidectomy, or neither. The contralateral ear was assessed. Otoscopic, impedance, and audiometric findings were recorded preoperatively and at six and twelve months postoperatively. Subtraction of the no-surgery results indicates that at twelve months adenoidectomy produces otoscopic resolution of OME in 41.7% and no-peak/peak conversion of impedance in 29.8%. The hearing gain from adenoidectomy alone was similar to that resulting from insertion of a grommet alone, but the children having adenoidectomy required fewer reinsertions to maintain adequate subjective hearing thresholds in the treated ear (26% versus 54%). Tonsillectomy conferred no additional benefit. Without treatment there was a small but significant improvement in all indices at twelve months but not at six months postoperatively.", "A prospective controlled study was made on the effect of adenoidectomy performed on 105 children. For various reasons, mainly severe long-standing nasal obstruction, 29 children were omitted from the study. The remaining 76 children were randomly divided into two groups, one adenoidectomy, and one control. Both groups were slightly reduced in number due to drop out. Thus 36 adenoidectomized children were followed during one year and 35 children during two years. The corresponding numbers for the children in the control group were 37 and 33. The incidence of common cold, purulent and serous otitis media and moderate nasal obstruction was compared in the two groups. A considerable reduction in the incidence of these variables was observed in both groups. The occurrence of moderate nasal obstruction was reduced more among the operated than among the unoperated children. The difference was only slightly significant during the first and not at all during the second year. Regarding the other variables, the differences were not significant, implying that adenoidectomy seems to have no effect on the incidence of common cold, serous and purulent otitis media." ]

[ "16501947", "12205255", "15114551", "9347370", "9462190", "19321507", "16155386", "16143747", "16815649", "15274104", "15674409" ]

[ "Volume-controlled intermittent mandatory ventilation in preterm infants with hypoxemic episodes.", "Effects of volume-guaranteed synchronized intermittent mandatory ventilation in preterm infants recovering from respiratory failure.", "Impact of targeted-volume ventilation on lung inflammatory response in preterm infants with respiratory distress syndrome (RDS).", "Patient-initiated, pressure-regulated, volume-controlled ventilation compared with intermittent mandatory ventilation in neonates: a prospective, randomised study.", "Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome.", "Long term follow-up of very low birthweight infants from a neonatal volume versus pressure mechanical ventilation trial.", "Effects of volume-targeted synchronized intermittent mandatory ventilation on spontaneous episodes of hypoxemia in preterm infants.", "Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low-birth-weight infants: a randomized controlled trial.", "Impact of volume guarantee ventilation on arterial carbon dioxide tension in newborn infants: a randomised controlled trial.", "Volume guarantee: stability of tidal volume and incidence of hypocarbia.", "Is there an advantage of using pressure support ventilation with volume guarantee in the initial management of premature infants with respiratory distress syndrome? A pilot study." ]

[ "To test the hypothesis in ventilated very low birth weight infants with frequent hypoxemic episodes that volume-controlled synchronized intermittent mandatory ventilation (SIMV) vs. pressure-controlled SIMV reduces by at least 20% the time with hypoxemia (defined as SpO(2)<80%).\n Randomized cross-over design.\n University-based tertiary neonatal intensive care unit.\n 15 mechanically ventilated very low birth weight infants with frequent hypoxemic episodes.\n The infants were exposed in random order to volume-controlled and pressure-controlled SIMV for 4 h each. The target tidal volume during volume-controlled SIMV was matched to the tidal volume measured during pressure-controlled SIMV. FIO(2) was adjusted using uniform criteria to maintain SpO(2) within the target range (SpO(2) 80-92%).\n Primary outcome measure was the time with an SpO(2)<80%. Although tidal volume was maintained better during desaturations with volume-controlled SIMV, there was neither a significant difference in time with an SpO(2)<80% (expressed as proportion of total experimental time; median, interquartile range)-volume-control 10.6% (9.2-13.7%) vs. pressure-control 10.8% (8.3-13.3%)-nor in FIO(2) exposure. During volume-controlled SIMV the infants spent less time with an SpO(2) above the target range and had fewer associated bradycardias.\n Volume-controlled SIMV did not decrease the time with an SpO(2)<80%, although tidal volume was better maintained during these episodes and bradycardias were less frequent than with pressure-controlled SIMV in this population of very low birth weight infants with frequent hypoxemic episodes.", "Volume guarantee (synchronized intermittent mandatory ventilation [SIMV]+VG) is a novel mode of SIMV for automatic adjustment of the peak inspiratory pressure to ensure a minimum set mechanical tidal volume (V(T mech)). The objective of this study was to compare the effects of SIMV+VG with conventional SIMV on ventilation and gas exchange in a group of very low birth weight infants recovering from acute respiratory failure.\n Nine infants were initially studied during 2 consecutive 60-minute ventilatory modalities of conventional SIMV (ventilator settings by clinical team) and SIMV+VG 4.5 (V(T mech) set at 4.5 mL/kg) in random order. Eight additional infants were studied during the same ventilatory modalities plus 1 additional epoch consisting of SIMV+VG 3.0 (V(T mech) set at 3.0 mL/kg).\n Peak inspiratory pressure was significantly lower during SIMV+VG 3.0. Mean airway pressure, V(T mech), number of large V(T mech) (>7 mL/kg), and mechanical minute ventilation (V'(E)) were reduced during SIMV+VG 4.5 compared with SIMV and were further reduced during SIMV+VG 3.0. Spontaneous V'(E) increased during SIMV+VG 4.5 and was even higher during SIMV+VG 3.0. The resulting total V'(E) was higher during both SIMV+VG modes compared with SIMV. Arterial oxygen saturation by pulse oximetry, transcutaneous carbon dioxide tension, and fraction of inspired oxygen did not differ significantly, although transcutaneous carbon dioxide tension increased slightly during SIMV+VG 3.0.\n The short-term use of SIMV+VG resulted in automatic weaning of the mechanical support and enhancement of the spontaneous respiratory effort while maintaining gas exchange relatively unchanged in comparison to conventional SIMV.", "Volutrauma and pulmonary inflammation are thought to be the most important predisposing factors of chronic lung disease (CLD), a major complication of prematurity. A new option in patient-triggered ventilation (PTV), the volume guarantee (VG), a volume-targeted ventilation, seems to be a promising approach in reducing the risk of CLD, by limiting lung inflammatory injury and volutrauma. Our aim was to evaluate lung inflammatory response in preterm infants with respiratory distress syndrome (RDS), mechanically ventilated with and without VG, as measured by proinflammatory cytokines (IL-6, IL-8, and TNF-alpha) in tracheobronchial aspirate (TA) fluid. Fifty-three preterm infants (GA = 25-32 weeks) with RDS were randomized at birth to be ventilated using pressure support ventilation (PSV) with VG (Vt = 5 ml/kg) (n = 30) and without VG (n = 23) (Draeger Babylog 8000 Plus, 5.n). IL-6, IL-8, and TNF-alpha were determined by ELISA in TA samples on days 1, 3, and 7 of life. We observed a significant difference (ANOVA) in IL-8 and IL-6 levels on day 3 between the two groups (P < 0.05), and an increasing significative trend in IL-8 values in PSV group (P < 0.05). Mechanical ventilation lasted longer in the PSV group (12.3 +/- 3 vs. 8.8 +/- 3 days) (P = no significance). In conclusion, these preliminary data suggest a role for volume-targeted ventilatory strategy in reducing acute inflammatory response in preterm infants with RDS. Further studies are required in order to define whether this ventilatory strategy prevents lung injury.\n Copyright 2004 Wiley-Liss, Inc.", "To compare the effects of patient-initiated, pressure-regulated, volume-controlled ventilation (PRVC) with pressure-preset intermittent mandatory ventilation (IMV) in neonates with respiratory failure.\n Randomised, prospective study.\n Intensive care unit (14 beds) in a 300-bed paediatric teaching hospital.\n 60 neonates with respiratory distress syndrome (RDS) or congenital pneumonia, weighing < 2500 g and requiring mechanical ventilation.\n Ventilatory support until extubation via either IMV (n = 30) or PRVC (n = 27). In PRVC, the tidal volume (VT) was preset and pressure-controlled breaths delivered with peak inspiratory pressure values adapted to achieve the preset VT.\n Main outcome measures were duration of ventilation and incidence of bronchopulmonary dysplasia (BPD). Pulmonary air leaks and intraventricular haemorrhage (IVH) were considered major adverse effects. Demographic data, ventilation parameters and arterial/alveolar oxygen tension ratio were similar at randomisation. Duration of ventilation and incidence of BPD were not decreased by the use of PRVC. Air leaks occurred in 3 neonates in the PRVC group and in 7 babies treated with IMV (NS). The incidence of IVH grade > II was lower in babies treated with PRVC (p < 0.05). In a subgroup of neonates weighing < 1000 g, the duration of ventilation and incidence of hypotension were reduced in the PRVC group (p < 0.05).\n Patient-initiated, pressure-regulated, volume-controlled ventilation can be safely used in neonates and may contribute to a lower incidence of complications.", "Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients.", "A previous randomised trial showed volume controlled ventilation (VCV) was efficacious in ventilating very preterm and extremely low birthweight babies.\n To compare long term survival, pulmonary morbidities and gross neurodevelopmental outcomes of babies randomised to either VCV or pressure limited ventilation (PLV) for treatment of respiratory distress syndrome.\n Masked evaluation of health status, including frequency of respiratory illness, use of medications, hospital admissions, and gross neurodevelopmental status were obtained using a structured parental questionnaire and verification from medical records.\n 94 of 109 children (86%) survived to discharge. Three died after discharge (2 VCV, 1 PLV). Modality of ventilation did not affect overall mortality; seven VCV children died (12%) versus 11 PLV (21%) (OR 0.5 (95% CI 0.1 to 1.4), p = 0.13). Respiratory abnormalities were present in 32 (37%), and 26 (30%) required hospital readmission. There was no significant difference in readmission rates between the two groups: VC 13/45 (29%) and PLV 19/40 (47%) (OR 0.4 (0.1 to 1.1), p = 0.07). Modality of ventilation did not affect frequency of respiratory illness: VC 12 (27%) and PLV 14 (35%) (OR 0.46 (0.1 to 1.1), p = 0.09). However, significantly fewer VCV children (13%, n = 6) compared to PLV children (32%, n = 13) required treatment with inhaled steroids/bronchodilators (OR 0.3 (0.1 to 0.9), p = 0.04). Nine children had severe neurodevelopmental disability (cerebral palsy, blindness, deafness) (9.8%; 3 VCV, 6 PLV 6) (OR 0.4 (0.09 to 1.7)).\n The efficacy of VCV in very preterm and low birth babies appears to be maintained on longer term evaluation.", "BACKGROUND: Hypoxemic episodes in ventilated preterm infants are frequently caused by reduced ventilation due to a decrease in lung volume and acute worsening of respiratory mechanics. OBJECTIVE: To compare the efficacy of conventional time-cycled, pressure-limited flow synchronized intermittent mandatory ventilation (SIMV) and volume-targeted SIMV (VT-SIMV) in reducing the frequency and severity of these episodes. METHODS: SIMV and VT-SIMV were compared in preterm infants with frequent spontaneous episodes of hypoxemia. VT-SIMV was provided with the Draeger Babylog 8000plus ventilator in volume-guarantee mode. Results: In all, 32 infants (birth weight 668 +/- 126 g, gestational age 24.8 +/- 1.1 weeks, age 37.5 +/- 17.3 days) were studied during 2-hour periods of SIMV and VT-SIMV in random sequence. In an initial phase, a group of 12 infants was supported during VT-SIMV with a target tidal volume of 4.5 ml/kg (VT-SIMV 4.5). A planned interim analysis did not show differences in frequency and duration of hypoxemia between VT-SIMV 4.5 and SIMV, and the initial phase was stopped. In a second phase of the study, 20 infants were studied while supported with a target tidal volume of 6.0 ml/kg during VT-SIMV (VT-SIMV 6.0). In the second phase of the study, the frequency of the hypoxemic episodes did not change but the mean episode duration was shorter during VT-SIMV compared to SIMV. The proportion of mechanical breaths with small tidal volumes (< or =3 ml/kg) was reduced during VT-SIMV 6.0 versus SIMV, while the peak inspiratory pressure and mean airway pressure were increased. Conclusion: VT-SIMV did not reduce the frequency of hypoxemic episodes, but VT-SIMV 6.0 was effective in reducing the duration of the hypoxemic episodes.", "To test the hypothesis that pressure-regulated volume control (PRVC), an assist/control mode of ventilation, would increase the proportion of very low-birth-weight infants who were alive and extubated at 14 days of age as compared with synchronized intermittent mandatory ventilation (SIMV).\n Ventilated infants with birth weight of 500 to 1249 g were randomized at less than 6 hours of age either to pressure-limited SIMV or to PRVC on the Servo 300 ventilator (Siemens Electromedical Group, Danvers, Mass). Infants received their assigned mode of ventilation until extubation, death, or meeting predetermined failure criteria.\n Mean +/- SD birth weights were similar in the SIMV (888 +/- 199 g, n = 108) and PRVC (884 +/- 203 g, n = 104) groups. No differences were detected between SIMV and PRVC groups in the proportion of infants alive and extubated at 14 days (41% vs 37%, respectively), length of mechanical ventilation in survivors (median, 24 days vs 33 days, respectively), or the proportion of infants alive without a supplemental oxygen requirement at 36 weeks' postmenstrual age (57% vs 63%, respectively). More infants receiving SIMV (33%) failed their assigned ventilator mode than did infants receiving PRVC (20%). Including failure as an adverse outcome did not alter the overall outcome (39% of infants in the SIMV group vs 35% of infants in the PRVC group were alive, extubated, and had not failed at 14 days).\n In mechanically ventilated infants with birth weights of 500 to 1249 g, using PRVC ventilation from birth did not alter time to extubation.", "To compare the effects of the two modes of ventilation, synchronous intermittent positive pressure ventilation (SIPPV) and SIPPV with Volume Guarantee (VG), on arterial carbon dioxide tension (PaCO(2)) immediately after neonatal unit admission.\n Randomised study of ventilation mode for premature inborn infants admitted to two tertiary neonatal units. After admission, infants were randomised to receive either SIPPV or VG using a Dräger Babylog 8000 plus ventilator. In the SIPPV group, peak airway pressure was set clinically. In the VG group, desired tidal volume was set at 4 ml/kg, with the ventilator adjusting peak inspiratory pressure to deliver this volume. The study was completed once the first arterial PaCO(2) was available, with the desirable range defined as 5-7 kPa.\n PaCO(2) was significantly higher in the VG group (VG: 5.7 kPa, SIPPV: 4.9 kPa; p=0.03). The VG group had fewer out-of-range PaCO(2) values (VG: 42%, SIPPV: 57%) and fewer instances of hypocarbia <5 kPa (VG: 32%, SIPPV: 57%) but neither difference achieved statistical significance. Regression analysis showed PaCO(2) was negatively correlated with gestation (r=-0.41, p=0.01) and also with the mode of ventilation (r=0.32, p<0.05). In the VG group, all infants 23-25 weeks' gestation had out-of-range PaCO(2) values. VG significantly reduced the incidence of out-of-range PaCO(2) and hypocarbia in infants over 25 weeks' gestation (VG: 27%, SIPPV: 61%; p<0.05).\n Using this strategy, VG appears feasible in the initial stabilisation of infants over 25 weeks' gestation, with a halving of the incidence of hypocarbia. In the small number of babies studied below this gestation, VG was not found to be effective.", "Excessive tidal volume (V(T)) can lead to lung injury, hypocarbia, and neurologic damage. Volume guarantee (VG) uses exhaled V(T) as the control variable to reduce the risk of volutrauma and more closely control PaCO(2). Our objective was to test the hypothesis that VG combined with assist/control (A/C) will maintain PaCO(2) and V(T) within target range more consistently than assist/control alone during the first 72 hr of life in ventilated preterm infants. Eligible infants were randomly assigned to A/C + VG or A/C alone. Data were recorded directly from the pressure and volume module of the Draeger Babylog 8000+ ventilator. Arterial blood gases were obtained every 2-6 hr, as clinically indicated. In A/C, inspiratory pressure was adjusted to achieve a V(T) of 4-6 ml/kg. In VG, the target V(T) was 5 ml/kg. Subsequent adjustments were made by the clinical team in response to arterial blood gas measurements (ABG). Proportion of breaths and PaCO(2) values outside the target range were compared by chi(2), and continuous variables by t-test. There were no differences in demographic or baseline ventilator variables between the 18 infants in the two groups. For 1,805/11,950 breaths (15.1%), V(T) was > target with A/C + VG, vs. 2,503/9,853 (25.4%) with A/C (P < 0.001). V(T) was < target for 21.7% of breaths with A/C + VG, vs. 35.7% with A/C (P < 0.001). Twenty percent of PaCO(2) values were < target, with A/C + VG vs. 36.3% with A/C, P < 0.05. The proportion of PaCO(2) values > target was similar in the two groups. Oxygenation and mean pH were not different. No complications related to mechanical ventilation were observed. In conclusion, VG significantly reduced hypocarbia and excessively large V(T). This suggests the potential to reduce pulmonary and neurologic complications of mechanical ventilation. Larger studies are needed to establish safety and demonstrate such benefits.\n Copyright 2004 Wiley-Liss, Inc.", "To evaluate the feasibility of using the pressure support ventilation with volume guarantee (PSV-VG) as an initial ventilatory mode in preterm infants with respiratory distress syndrome (RDS) after surfactant treatment to achieve accelerated weaning of peak inspiratory pressure (PIP) and mean airway pressure (MAP).\n Initial 24-hour ventilatory parameters were compared in two groups of preterm infants managed by PSV-VG and the synchronized intermittent mandatory ventilation (SIMV) mode in a randomized controlled pilot study after surfactant treatment for RDS. A total of 16 babies were randomized to PSV-VG (1198+/-108 g [mean+/-SEM]; 27.9+/-0.6 weeks) and 18 babies to SIMV (birth weight 1055+/-77 g; gestational age 27.4+/-0.5 weeks). Repeated measures analysis of variance was used to compare serial values of PIP and MAP in the two groups.\n The PIP and MAP decreased over time (p<0.001) during the first 24 hours after surfactant administration in both groups but the decrease in MAP was faster in the SIMV group compared to PSV-VG group (p=0.035). The median numbers of blood gases during the first 24 hours were four and two in the SIMV and PSV-VG groups, respectively (p<0.001). The overall outcomes were not significantly different between the two groups.\n PSV-VG did not offer any ventilatory advantage over SIMV in the initial management of surfactant-treated premature newborns with RDS except for minimizing the number of blood gases." ]

[ "11810100", "11120515", "937989", "3336553", "6914388", "10870784", "16055571", "6829657", "10647530" ]

[ "Continuing regular exercise during pregnancy: effect of exercise volume on fetoplacental growth.", "Beginning regular exercise in early pregnancy: effect on fetoplacental growth.", "Heart volume and physical fitness of parturients.", "The effect of participation in a regular exercise program upon aerobic capacity during pregnancy.", "Swimming and physical fitness during pregnancy.", "Antenatal exercise and birthweight.", "Aerobic exercise and submaximal functional capacity in overweight pregnant women: a randomized trial.", "Maternal and fetal responses to a maternal aerobic exercise program.", "Physical and psychological changes with vigorous exercise in sedentary primigravidae." ]

[ "The purpose of this study was to test the null hypothesis that the volume of exercise at different times during pregnancy has no effect on fetoplacental growth.\n Seventy-five women who exercised regularly were evaluated before pregnancy and randomly assigned at 8 weeks' gestation to one of 3 exercise regimens for the remainder of pregnancy. Primary outcome variables included placental growth rate, birth weight, and placental volume at term.\n The offspring of the women who were randomly assigned to a high volume of exercise in mid and late pregnancy were significantly lighter (3.39 kg vs 3.81 kg) and thinner (8.3% fat vs 12.1% fat) than those offspring born of women who were randomly assigned to reduce their exercise volume after the 20th week. Maternal weight gain, fresh placental volumes, and histomorphometric indices of placental function were greater in the high-low group.\n These data indicate that a high volume of moderate-intensity, weight-bearing exercise in mid and late pregnancy symmetrically reduces fetoplacental growth, whereas a reduction in exercise volume enhances fetoplacental growth with a proportionally greater increase in fat mass than in lean body mass.", "Our purpose was to test the null hypothesis that beginning regular, moderate-intensity exercise in early pregnancy has no effect on fetoplacental growth. Study Design: Forty-six women who did not exercise regularly were randomly assigned at 8 weeks either to no exercise (n = 24) or to weight-bearing exercise (n = 22) 3 to 5 times a week for the remainder of pregnancy. Outcome variables included antenatal placental growth rate and neonatal and placental morphometric measurements.\n The offspring of the exercising women were significantly heavier (corrected birth weight: 3.75 +/- 0.08 kg vs 3.49 +/- 0.07 kg) and longer (51.8 +/- 0.3 cm vs 50.6 +/- 0.3 cm) than those born to control women. The difference in birth weight was the result of an increase in both lean body mass and fat mass. In addition, midtrimester placental growth rate was faster (26 +/- 2 cm(3)/wk vs 21 +/- 1 cm(3)/wk) and morphometric indexes of placental function were greater in the exercise group. There were no significant differences in neonatal percentage body fat, head circumference, ponderal index, or maternal weight gain.\n These data indicate that beginning a moderate regimen of weight-bearing exercise in early pregnancy enhances fetoplacental growth.", "One hundred and three primigravidae were studied to establish the correlation between physical fitness and heart volume. Twenty-three of the mothers were allocated at random to the exercise group and 21 to control group 1, between the 10th and 14th weeks of pregnancy. In addition, 59 mothers were allocated to control group 2, which was formed two weeks before term. The exercise group underwent a rather strenuous training programme during pregnancy. Physical fitness was measured by work tests on a bicycle ergometer two weeks before term. The heart volume was determined radiologically on the 6th day post partum. There was a positive correlation between physical fitness and the relative heart volume, which was greatest when physical fitness was measured by a method which takes the level of training into consideration. The relative heart volume of the exercise group was almost significantly greater than that of control group 1. The physical performance of the exercise group was very significantly greater than in the control groups. There was no significant correlation between either physical fitness or relative heart volume and the duration of pregnancy or the weight of newborn.", "This study examined the questions of whether pregnancy decreases physical fitness, as measured by maximal oxygen consumption, between the second and third trimesters, and whether maintaining a regular exercise program during the second half of pregnancy affects fitness. At the beginning of their second trimester, pregnant women were randomly assigned to either a nonexercising control group or an exercising group. They completed a maximal progressive exercise test on a cycle ergometer at 20 and 30 weeks, during which pulmonary parameters of aerobic capacity were measured. The exercising group demonstrated greater improvement in aerobic capacity than did the control group, manifested by increases in tidal volume and oxygen consumption and a stable ventilatory equivalent for oxygen. Pregnancy did not reduce maximal oxygen consumption between the second and third trimesters of pregnancy.", "nan", "Does strenuous antenatal exercise reduce birthweight? Does reducing maternal exercise increase birthweight? What to advise about exercise during pregnancy? We recruited 117 women who intended to exercise 5 or more times weekly during pregnancy to a study of whether reducing the amount of maternal exercise during pregnancy is associated with an increase in birthweight. Only 61/117 (52%) of women agreed to be randomised to either continue or to reduce (to 3 or fewer sessions of exercise weekly) their intended pregnancy exercise program. Most women who refused randomisation did not want to risk being asked to reduce their exercise during pregnancy. Within the randomised trial, there was no statistically significant difference between the mean birthweight of babies born to women who continued and those who reduced their intended exercise program. The high rate of refusal of randomisation limits the power of the study to find a difference in birthweight, limits the generalisability of the results and shows that many women intending to exercise at this level during pregnancy have an uncompromising attitude to exercise.", "To evaluate the effects of aerobic training on submaximal cardiorespiratory capacity in overweight pregnant women.\n We conducted a randomized clinical trial in a referral center prenatal clinic during the period 2000-2002. Of 132 overweight (body mass index 26-31 kg/m2) but otherwise healthy volunteers, at 20 years of age or older, with gestational age of 20 weeks or less, and without diabetes or hypertension, 92 consented to participate and were randomized. Intervention consisted of 3 one-hour aerobic exercise sessions per week; the control group received weekly relaxation and focus group discussions. The main outcome measure was submaximal exercise capacity evaluated by oxygen uptake at the anaerobic (first ventilatory) threshold during cardiopulmonary treadmill testing 12 weeks after randomization.\n Oxygen uptake at the anaerobic threshold increased 18% (15.9 +/- 2.6 to 18.1 +/- 3.1 mL . min(-1) . kg(-1)) in the exercise group but decreased 16% (16.9 +/- 3.0 to 15.8 +/- 2.6 mL . min(-1) . kg(-1)) among the control group. Oxygen consumption at the anaerobic threshold, adjusted through analysis of covariance for baseline oxygen uptake, was 2.68 (95% confidence interval 1.23 to 4.12) mL . min(-1) . kg(-1) greater in the exercise group. Women in the exercise group were approximately 5 times more likely than those in the control group to have regular or good cardiorespiratory capacity (12/38 versus 2/38; relative risk 5.2, 95% confidence interval 1.2 to 22.0, number needed to treat 5).\n Aerobic training in overweight pregnant women substantially increases submaximal exercise capacity, overcoming the otherwise negative effects of pregnancy in this regard. Additional studies are required to evaluate its effect on major clinical outcomes.", "To investigate the effects of exercise on the pregnant woman and her fetus, 20 pregnant women were studied during the second and third trimesters. Twelve of the women participated in an aerobic exercise program while eight women did not perform any regular exercise and served as a control group. On the basis of submaximal exercise test results, an 18% improvement and a 4% decline in absolute aerobic capacity (liters of oxygen per minute) were observed in the exercise and control groups, respectively. Functional aerobic capacity (milliliters of oxygen per kilogram per minute) rose 8% in the exercise group and declined 10% in the control group. A small but significant rise in fetal heart rate was measured during the exercise sessions. A comparison of pregnancy outcome of the two groups showed no differences in labor duration, Apgar scores, or fetal growth.", "The present study examined the effects of exercise on physical and psychological variables in sedentary primigravidae (PRA).\n A total of nine women randomly assigned to an exercise (E) (mean age = 31.3 +/- 3.1 yr) and six subjects randomly assigned to a control (C) group (mean age = 27.8 +/- 3.1 yr) fulfilled all requirements for the study. Exercise included a variety of exercise activities performed to a target heart rate of 150-156 beats x min(-1), three times per week for 15 wk.\n Results showed no significant differences between E and C groups in physical characteristics initially. A repeated measures ANOVA showed a significant group effect (P < 0.05) and a significant group by time interaction (P = 0.001) with the E group showing a significantly longer amount of time on the PWC150 test than the C group. There was no significant group, time, or group by time interaction for lactate accumulation. This occurred, despite the fact that the E group spent 56% longer on the PWC150 test and the C group spent 30% less time on the same test at the conclusion of the study. Finally, the E group in comparison to the C group showed more favorable improvements in several items related to health and well-being on the Body Cathexis Scale. There were no significant differences between E and C groups in any pregnancy outcome measures. All babies were delivered healthy at term.\n These data suggest that a vigorous exercise program can lead to significant improvements in aerobic fitness at similar lactate concentrations compared to a control group and can be well tolerated by low risk sedentary PRA without any deleterious effects occurring to herself or unborn child." ]

[ "19583645", "7650352", "8409351", "20417038", "16457423", "18317710", "529194" ]

[ "An educational intervention to improve women's ability to cope with childbirth.", "Effect of relaxation with guided imagery on anxiety, depression, and self-esteem in primiparas.", "An exploratory study of the effectiveness of a relaxation with guided imagery protocol.", "Effects of relaxation on psychobiological wellbeing during pregnancy: a randomized controlled trial.", "The effects of acute relaxation on indices of anxiety during pregnancy.", "Effects of a mindfulness-based intervention during pregnancy on prenatal stress and mood: results of a pilot study.", "Preparation courses for childbirth in primipara. A comparison." ]

[ "To test the effectiveness of an efficacy-enhancing educational intervention to promote women's self-efficacy for childbirth and coping ability in reducing anxiety and pain during labour.\n The evidence of the effective application of the self-efficacy theory in health-promoting interventions has been well established. Little effort has been made by health professionals to integrate self-efficacy theory into childbirth care.\n Randomised controlled trial.\n An efficacy-enhancing educational intervention based on Bandura's self-efficacy theory was evaluated. The eligible Chinese first-time pregnant women were randomly assigned to either an experimental group (n = 60) or a control group (n = 73). The experimental group received two 90-minute sessions of the educational programme in between the 33rd-35th weeks of pregnancy. Follow-up assessments on outcome measures were conducted within 48 hours after delivery. The short form of the Chinese Childbirth Self-Efficacy Inventory was used to measure maternal self-efficacy prior to labour. Evaluation of pain and anxiety during the three stages of labour and performance of coping behaviour during labour were measured by the Visual Analogue Scale and Childbirth Coping Behaviour Scale respectively.\n The experimental group was significantly more likely than the control group to demonstrate higher levels of self-efficacy for childbirth (p < 0.0001), lower perceived anxiety (p < 0.001, early stage and p = 0.02, middle stage) and pain (p < 0.01, early stage and p = 0.01, middle stage) and greater performance of coping behaviour during labour (p < 0.01).\n The educational intervention based on Bandura's self-efficacy theory is effective in promoting pregnant women's self-efficacy for childbirth and reducing their perceived pain and anxiety in the first two stages of labour.\n Relief of pain and anxiety is an important issue for both women and childbirth health professionals. The efficacy-enhancing educational intervention should be further developed and integrated into childbirth educational interventions for promoting women's coping ability during childbirth.", "A pretest-posttest experimental design with a convenience sample of 60 subjects was used to examine the effects of a relaxation with guided imagery protocol on anxiety, depression, and self-esteem in primiparas during the first 4 weeks of the postpartum period. The results showed that the experimental group had less anxiety and depression and greater self-esteem than did the control group at the end of the period. Positive correlations were obtained between anxiety and depression; negative correlations between self-esteem and anxiety and depression. All findings were significant at the .05 level.", "An exploratory study was done to examine the effectiveness of a relaxation with guided imagery protocol in reducing anxiety and depression and increasing self-esteem in new mothers during the first 4 weeks postpartum. The results indicate that anxiety and depression declined and self-esteem increased in subjects in both the experimental and control groups over the 4-week period. However, the decline in anxiety and the increase in self-esteem was greater in the experimental group than in the control group. The decline in depression was about the same in both groups. Further study, using more precise methodology and instrumentation, needs to be done to verify the results.", "Prenatal maternal stress is associated with adverse birth outcomes and may be reduced by relaxation exercises. The aim of the present study was to compare the immediate effects of two active and one passive 10-min relaxation technique on perceived and physiological indicators of relaxation. 39 healthy pregnant women recruited at the outpatient department of the University Women's Hospital Basel participated in a randomized controlled trial with an experimental repeated measure design. Participants were assigned to one of two active relaxation techniques, progressive muscle relaxation (PMR) or guided imagery (GI), or a passive relaxation control condition. Self-reported relaxation on a visual analogue scale (VAS) and state anxiety (STAI-S), endocrine parameters indicating hypothalamic-pituitary-adrenal (HPA) axis (cortisol and ACTH) and sympathetic-adrenal-medullary (SAM) system activity (norepinephrine and epinephrine), as well as cardiovascular responses (heart rate, systolic and diastolic blood pressure) were measured at four time points before and after the relaxation exercise. Between group differences showed, that compared to the PMR and control conditions, GI was significantly more effective in enhancing levels of relaxation and together with PMR, GI was associated with a significant decrease in heart rate. Within the groups, passive as well as active relaxation procedures were associated with a decline in endocrine measures except epinephrine. Taken together, these data indicate that different types of relaxation had differential effects on various psychological and biological stress systems. GI was especially effective in inducing self-reported relaxation in pregnant women while at the same time reducing cardiovascular activity.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "Antenatal maternal anxiety has adverse effects on the fetus and the child. In this study we determined whether a short period of directed or of passive relaxation reduced maternal self-rated anxiety, heart rate, plasma catecholamines, cortisol and uterine artery resistance index, in pregnant women.\n Fifty-eight women (28-32 wks gestation) were assigned randomly to a session of directed active or passive (sitting quietly) relaxation. Spielberger self-rating anxiety questionnaires were completed, and a venous blood sample taken, before and after a Doppler scan.\n Both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, but the effect was significantly greater with the active relaxation. In contrast, the passive relaxation significantly reduced noradrenaline levels whereas active did not. Adrenaline levels were not changed significantly with either type of relaxation. Both methods significantly reduced cortisol, with a trend for the passive to have a greater effect. The active relaxation had no effect on uterine artery blood flow, whereas there was a statistically significant, but clinically negligible, increase in mean resistance index after passive relaxation.\n Both methods reduced maternal State Anxiety and heart rate, the active method more so. However there was a striking lack of correlation with the other biological indices studied. In order to reduce specific biological effects of anxiety during pregnancy, different methods may be needed from those which are most effective at reducing subjective anxiety.", "Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother-infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial (n=31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p<0.05) and negative affect (effect size, 0.83; p<0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy.", "nan" ]

[ "18628946", "18043319", "8245525", "20595141", "12045493", "19911990", "19662523", "19901865", "17413536", "19752714", "20168206", "15851918", "19002268" ]

[ "Willingness of men who have sex with men (MSM) in the United States to be circumcised as adults to reduce the risk of HIV infection.", "Circumcision status and HIV infection among Black and Latino men who have sex with men in 3 US cities.", "The association between circumcision status and human immunodeficiency virus infection among homosexual men.", "Circumcision among men who have sex with men in Scotland: limited potential for HIV prevention.", "HIV, syphilis and heterosexual bridging among Peruvian men who have sex with men.", "Circumcision and risk of sexually transmissible infections in a community-based cohort of HIV-negative homosexual men in Sydney, Australia.", "High HIV prevalence among men who have sex with men in Soweto, South Africa: results from the Soweto Men's Study.", "The association between lack of circumcision and HIV, HSV-2, and other sexually transmitted infections among men who have sex with men.", "Prevalence of circumcision and herpes simplex virus type 2 infection in men in the United States: the National Health and Nutrition Examination Survey (NHANES), 1999-2004.", "Circumcision and risk of HIV infection in Australian homosexual men.", "Circumcision status and HIV infection among MSM: reanalysis of a Phase III HIV vaccine clinical trial.", "Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States.", "Male circumcision and HIV status among Latino immigrant MSM in New York City." ]

[ "Circumcision reduces HIV acquisition among heterosexual men in Africa, but it is unclear if circumcision may reduce HIV acquisition among men who have sex with men (MSM) in the United States, or whether MSM would be willing to be circumcised if recommended.\n We interviewed presumed-HIV negative MSM at gay pride events in 2006. We asked uncircumcised respondents about willingness to be circumcised if it were proven to reduce risk of HIV among MSM and perceived barriers to circumcision. Multivariate logistic regression was used to identify covariates associated with willingness to be circumcised.\n Of 780 MSM, 133 (17%) were uncircumcised. Of these, 71 (53%) were willing to be circumcised. Willingness was associated with black race (exact odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.3-9.8), non-injection drug use (OR: 6.1, 95% CI: 1.8-23.7) and perceived reduced risk of penile cancer (OR: 4.7, 95% CI: 2.0-11.9). The most commonly endorsed concerns about circumcision were post-surgical pain and wound infection.\n Over half of uncircumcised MSM, especially black MSM, expressed willingness to be circumcised. Perceived risks and benefits of circumcision should be a part of educational materials if circumcision is recommended for MSM in the United States.", "To examine characteristics of circumcised and uncircumcised Latino and black men who have sex with men (MSM) in the United States and assess the association between circumcision and HIV infection.\n Using respondent-driven sampling, 1154 black MSM and 1091 Latino MSM were recruited from New York City, Philadelphia, and Los Angeles. A 45-minute computer-assisted interview and a rapid oral fluid HIV antibody test (OraSure Technologies, Bethlehem, PA) were administered to participants.\n Circumcision prevalence was higher among black MSM than among Latino MSM (74% vs. 33%; P < 0.0001). Circumcised MSM in both racial/ethnic groups were more likely than uncircumcised MSM to be born in the United States or to have a US-born parent. Circumcision status was not associated with prevalent HIV infection among Latino MSM, black MSM, black bisexual men, or black or Latino men who reported being HIV-negative based on their last HIV test. Further, circumcision was not associated with a reduced likelihood of HIV infection among men who had engaged in unprotected insertive and not unprotected receptive anal sex.\n In these cross-sectional data, there was no evidence that being circumcised was protective against HIV infection among black MSM or Latino MSM.", "To evaluate whether uncircumcised status is correlated with acquisition of human immunodeficiency virus (HIV), 502 homosexual men were surveyed; 85% were circumcised. HIV infection was significantly associated with uncircumcised status (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2, 3.8), nonwhite race, intravenous drug use, sexual contact with an intravenous drug user, number of male partners, frequency of unprotected receptive anal intercourse, and with history of genital herpes, anal herpes, or syphilis. Uncircumcised status was significantly associated with older age, nonwhite race, and history of syphilis; it was inversely associated with intravenous drug use. Using logistic regression analysis, the adjusted OR for the association between HIV infection and uncircumcised status was 2.0 (95% CI, 1.0, 4.0). Uncircumcised homosexual men had 2-fold increased risk of HIV infection. The role of circumcision as an intervention strategy to reduce sexual transmission of HIV warrants consideration.", "Male circumcision has been shown to reduce the risk of HIV acquisition among heterosexual men but the impact among men who have sex with men (MSM) is not known. In this paper, we explore the feasibility of research into circumcision for HIV prevention among MSM in Scotland.\n Anonymous, self-complete questionnaires and Orasure oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh.\n 1508 men completed questionnaires (70.5% response rate) and 1277 provided oral fluid samples (59.7% response rate). Overall, 1405 men were eligible for inclusion in the analyses. 16.6% reported having been circumcised. HIV prevalence was similar among circumcised and uncircumcised men (4.2% and 4.6%, respectively). Although biologically, circumcision is most likely to protect against HIV for men practising unprotected insertive anal intercourse (UIAI), only 7.8% (91/1172) of uncircumcised men reported exclusive UIAI in the past 12 months. Relatively few men reported being willing to participate in a research study on circumcision and HIV prevention (13.9%), and only 11.3% of uncircumcised men did so.\n The lack of association between circumcision and HIV status, low levels of exclusive UIAI, and low levels of willingness to take part in circumcision research studies suggest circumcision is unlikely to be a feasible HIV prevention strategy for MSM in the UK. Behaviour change should continue to be the focus of HIV prevention in this population.", "To determine prevalence of and risk factors associated with HIV and syphilis seropositivity and estimate incidence of HIV infection among Peruvian men who have sex with men (MSM) and characterize behaviors of men who report sex with both men and women ('bridgers').\n Cross-sectional study of MSM in Lima, Peru.\n Four-hundred and fifty-one MSM (of whom 442 responded to the question regarding sexual orientation) recruited through street outreach. Each was interviewed and underwent serologic testing for syphilis and HIV, including the less sensitive enzyme immunoassay test to estimate HIV incidence.\n Overall, HIV and syphilis prevalence were 18.5% and 16.0%, respectively, with highest prevalence among cross-dressers (33.3% and 51.1%, respectively). The estimated overall HIV seroincidence was 11.2% per year (95% confidence interval, 4.8-23.6). Overall, 47.1% of men reported ever having sex with a woman: 78.6% of men self-identifying as heterosexuals, 85.1% of bisexuals, 35.5% of homosexuals, and 12.5% of cross-dressers. Of these, 26.5% were 'bridgers', of whom 55% reported two or more female partners during the last year. 'Bridgers' were less likely to have always used condoms during the past year for vaginal sex (17%) than for insertive anal sex with men (25.5%).\n Among MSM in Peru, HIV and syphilis prevalence and HIV incidence were high, especially among cross-dressers. The high prevalence of bisexuality and low rates of consistent condom use, especially with female sexual partners indicates potential HIV transmission into the heterosexual population.", "Circumcision status was examined as an independent risk factor for sexually transmissible infections (STIs) in the Health in Men cohort of homosexual men in Sydney.\n From 2001 through 2004, 1427 initially human immunodeficiency virus (HIV)-negative men were enrolled and followed up until mid-2007. All participants were offered annual STI testing. The history of STIs was collected at baseline, and information on sexual risk behaviors was collected every 6 months. At annual face-to-face visits, participants reported STI diagnoses received during the previous year.\n Circumcision was not associated with prevalent or incident herpes simplex virus 1, herpes simplex virus 2, or self-reported genital warts. There was also no independent association of circumcision with incident urethral gonorrhea or chlamydia. Being circumcised was associated with a significantly reduced risk of incident (hazard ratio, 0.35 [95% confidence interval, 0.15-0.84]) but not prevalent (odds ratio, 0.71 [95% confidence interval, 0.35-1.44]) syphilis. The association was somewhat stronger among men who reported predominantly insertive unprotected anal intercourse (hazard ratio, 0.10 [95% confidence interval, 0.01-0.82]).\n These are the first prospective data obtained from homosexual men to assess circumcision status as a risk factor for STIs. Circumcised men were at reduced risk of incident syphilis but no other prevalent or incident STIs. Circumcision is unlikely to have a substantial public health impact in reducing acquisition of most STIs in homosexual men.", "The Soweto Men's Study assessed HIV prevalence and associated risk factors among MSM in Soweto, South Africa. Using respondent driven sampling (RDS) recruitment methods, we recruited 378 MSM (including 15 seeds) over 30 weeks in 2008. All results were adjusted for RDS sampling design. Overall HIV prevalence was estimated at 13.2% (95% confidence interval 12.4-13.9%), with 33.9% among gay-identified men, 6.4% among bisexual-identified men, and 10.1% among straight-identified MSM. In multivariable analysis, HIV infection was associated with being older than 25 (adjusted odds ratio (AOR) 3.8, 95% CI 3.2-4.6), gay self-identification (AOR 2.3, 95% CI 1.8-3.0), monthly income less than ZAR500 (AOR 1.4, 95% CI 1.2-1.7), purchasing alcohol or drugs in exchange for sex with another man (AOR 3.9, 95% CI 3.2-4.7), reporting any URAI (AOR 4.4, 95% CI 3.5-5.7), reporting between six and nine partners in the prior 6 months (AOR 5.7, 95% CI 4.0-8.2), circumcision, (AOR 0.2, 95% CI 0.1-0.2), a regular female partner (AOR 0.2, 95% CI 0.2-0.3), smoking marijuana in the last 6 months (AOR 0.6, 95% CI 0.5-0.8), unprotected vaginal intercourse in the last 6 months (AOR 0.5, 95% CI 0.4-0.6), and STI symptoms in the last year (AOR 0.7, 95% CI 0.5-0.8). The results of the Soweto Men's Study confirm that MSM are at high risk for HIV infection, with gay men at highest risk. HIV prevention and treatment for MSM are urgently needed.", "Observational studies evaluating the association of circumcision and HIV infection among men who have sex with men (MSM) have yielded mixed results. We examined the relationship between circumcision and HIV, herpes simplex virus type-2 (HSV-2), syphilis, urethral gonorrhea, and urethral chlamydia among MSM stratified by anal sexual role.\n Between October 2001 and May 2006, 4749 MSM who reported anal intercourse in the previous 12 months attended the Public Health-Seattle and King County STD clinic for 8337 evaluations. Clinicians determined circumcision status by examination and anal sexual role in the previous year by interview. Blood samples were used to test HIV, syphilis, and HSV-2 serostatus. Urethral gonorrhea and chlamydia were tested by culture or nucleic acid amplification. We used generalized estimating equations to evaluate the association between circumcision and specific diagnoses, adjusted for race/ethnicity and age.\n Among the 3828 men whose circumcision status was assessed, 3241 (85%) were circumcised and 587 (15%) were not. The proportion of men newly testing HIV-positive or with previously diagnosed HIV did not differ by circumcision status when stratified by men's anal sexual role in the preceding year, even when limited to men who reported only insertive anal intercourse in the preceding 12 months (OR = 1.45; 95% CI: 0.30, 7.12). Similarly, we did not observe a significant association between circumcision status and the other sexually transmitted infections (STI).\n Our findings suggest that male circumcision would not be likely to have a significant impact on HIV or sexually transmitted infections acquisition among MSM in Seattle.", "To study the prevalence of circumcision in the United States and to examine the association between circumcision and herpes simplex virus Type 2 (HSV-2) infection.\n As part of National Health and Nutrition Examination Surveys from 1999 to 2004, 6174 men were interviewed about circumcision status and sexual behaviors, and were tested for HSV-2 antibodies. Medical artwork was used to aid the reporting of circumcision status.\n The overall prevalence of circumcision was 79% and varied by race/ethnicity (88% in non-Hispanic whites, 73% in non-Hispanic blacks, 42% in Mexican Americans, and 50% in others). For men born in the United States from 1940 through 1979, the prevalence of circumcision increased, with larger increases in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites; the prevalence of circumcision decreased significantly in those born in the 1980s (84%) compared to those born in 1970s (91%) (P <0.001). Circumcision status was not associated with sexual behaviors we assessed. In multivariate analyses, circumcision was not associated with HSV-2 infection (P = 0.47).\n The prevalence of circumcision apparently peaked in those born in the 1970s and declined in those born in the 1980s. Circumcision was not associated with HSV-2 infection.", "To assess circumcision status as a risk factor for HIV seroconversion in homosexual men.\n The Health in Men (HIM) study was a prospective cohort of homosexual men in Sydney, Australia. HIV-negative men (n = 1426) were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. Participants underwent annual HIV testing, and detailed information on sexual risk behaviour was collected every 6 months.\n HIV incidence in circumcised compared with uncircumcised participants, stratified by whether or not men predominantly practised the insertive role in anal intercourse.\n There were 53 HIV seroconversions during follow-up; an incidence of 0.78 per 100 person-years. On multivariate analysis controlling for behavioural risk factors, being circumcised was associated with a nonsignificant reduction in risk of HIV seroconversion [hazard ratio 0.78, 95% confidence interval (CI) 0.42-1.45, P = 0.424]. Among one-third of study participants who reported a preference for the insertive role in anal intercourse, being circumcised was associated with a significant reduction in HIV incidence after controlling for age and unprotected anal intercourse (UAI) (hazard ratio 0.11, 95% CI 0.03-0.80, P = 0.041). Those who reported a preference for the insertive role overwhelmingly practised insertive rather than receptive UAI.\n Overall, circumcision did not significantly reduce the risk of HIV infection in the HIM cohort. However, it was associated with a significant reduction in HIV incidence among those participants who reported a preference for the insertive role in anal intercourse. Circumcision may have a role as an HIV prevention intervention in this subset of homosexual men.", "Determine whether male circumcision would be effective in reducing HIV transmission among men who have sex with men (MSM).\n Retrospective analysis of the VAXGen VAX004 HIV vaccine clinical trial data.\n Survival analysis was used to associate time to HIV infection with multiple predictors. Unprotected insertive and receptive anal sex predictors were highly correlated, thus separate models were run.\n Four thousand eight hundred and eighty-nine participants were included in this reanalysis; 86.1% were circumcised. Three hundred and forty-two (7.0%) men became infected during the study; 87.4% were circumcised. Controlling for demographic characteristics and risk behaviors, in the model that included unprotected insertive anal sex, being uncircumcised was not associated with incident HIV infection [adjusted hazards ratio (AHR) = 0.97, confidence interval (CI) = 0.56-1.68]. Furthermore, while having unprotected insertive (AHR = 2.25, CI = 1.72-2.93) or receptive (AHR = 3.45, CI = 2.58-4.61) anal sex with an HIV-positive partner were associated with HIV infection, the associations between HIV incidence and the interaction between being uncircumcised and reporting unprotected insertive (AHR = 1.78, CI = 0.90-3.53) or receptive (AHR = 1.26, CI = 0.62-2.57) anal sex with an HIV-positive partner were not statistically significant. Of the study visits when a participant reported unprotected insertive anal sex with an HIV-positive partner, HIV infection among circumcised men was reported in 3.16% of the visits (80/2532) and among uncircumcised men in 3.93% of the visits (14/356) [relative risk (RR) = 0.80, CI = 0.46-1.39].\n Among men who reported unprotected insertive anal sex with HIV-positive partners, being uncircumcised did not confer a statistically significant increase in HIV infection risk. Additional studies with more incident HIV infections or that include a larger proportion of uncircumcised men may provide a more definitive result.", "Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.", "This study investigated protective effects of circumcision in a sample of immigrant Latino men who have sex with men (MSM). A survey in Portuguese, Spanish, or English was administered with computer-assisted self-interview technology with audio enhancement (A-CASI) to 482 MSM from Brazil (n=146), Colombia (n=169), and the Dominican Republic (n=167), living in the New York metropolitan area. Logistic regression revealed that after controlling for age, income, education, having had syphilis, having done sex work, and preferring the receptive role in anal intercourse, uncircumcised men were almost twice as likely to be HIV-positive as circumcised men. Follow-up analyses revealed, however, that the protective effects occurred only among the group of Colombian men." ]

[ "10715297", "7608801", "8365459", "2202792", "9406362", "8614377", "9024516", "7742759", "1968484" ]

[ "Prevention of central venous catheter-related infections and thrombotic events in immunocompromised children by the use of vancomycin/ciprofloxacin/heparin flush solution: A randomized, multicenter, double-blind trial.", "A randomized, controlled trial of the efficacy of a heparin and vancomycin solution in preventing central venous catheter infections in children.", "A prospective randomized study of prophylactic teicoplanin to prevent early Hickman catheter-related sepsis in patients receiving intensive chemotherapy for haematological malignancies.", "Prevention of bacteremia attributed to luminal colonization of tunneled central venous catheters with vancomycin-susceptible organisms.", "Peroperative teicoplanin for prevention of gram-positive infections in neutropenic patients with indwelling central venous catheters: a randomized, controlled study.", "Prevention of indwelling central venous catheter sepsis.", "Efficacy of a vancomycin solution to prevent bacteremia associated with an indwelling central venous catheter in neutropenic and non-neutropenic cancer patients.", "Central venous catheter-related infections after bone marrow transplantation in patients with malignancies: a prospective study with short-course vancomycin prophylaxis.", "Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients." ]

[ "To determine whether an antibiotic flush solution containing vancomycin, heparin, and ciprofloxacin (VHC) can prevent the majority of line infections.\n A prospective double-blind study was performed comparing VHC to vancomycin and heparin (VH) to heparin alone in 126 pediatric oncology patients.\n The 153 assessable lines resulted in 36,944 line days studied. There were 58 blood stream infections (43 gram-positive, 14 gram-negative, and one fungal). Forty were defined as line infections (31 heparin, three VH, six VHC). The time to develop a line infection was significantly increased using either antibiotic flush (VH, P =.011; VHC, P =.036). The rate of total line infections (VH, P =.004; VHC, P =.005), gram-positive line infections (VH, P =. 028; VHC, P =.022), and gram-negative line infections (VH, P =.006; VHC, P =.003) was significantly reduced by either VH or VHC. Sixty-two (41%) of the lines developed 119 occlusion episodes (heparin, 3.99 per 1,000 line days; VHC, 1.75 per 1,000 line days; P =.0005). Neither antibiotic could be detected after flushing, and no adverse events were detected, including increased incidence of vancomycin-resistant Enterococcus colonization or disease.\n The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care resources.", "To determine whether adding vancomycin to central venous catheter (CVC) flush solution would significantly reduce the incidence of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms.\n Fifty-five children with cancer and eight children given total parenteral nutrition by the surgery or nutrition support services were randomly assigned to receive a heparin CVC flush solution (n = 31) or a heparin-vancomycin CVC flush solution (n = 32).\n During 9158 catheter days, 6.5% of the patients in the heparin group and 15.6% of the patients in the heparin-vancomycin group had bacteremia attributable to luminal colonization with vancomycin-susceptible organisms (p = 0.43). The mean rates of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms were 0.6/1000 catheter days in the heparin group and 1.4/1000 catheter days in the heparin-vancomycin group (p = 0.25). There was no significant difference between the groups when the time to the first episode of bacteremia attributable to luminal colonization with a vancomycin-susceptible organism was compared by means of Kaplan-Meier survival estimates. Streptococcus viridans infection was not attributable to luminal colonization.\n The addition of vancomycin to heparin CVC flush solution did not reduce bacteremia with vancomycin-susceptible organisms. Bacteremia with Streptococcus viridans was not related to the use of a CVC.", "In all, 88 patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin, 400 mg, or no teicoplanin immediately before insertion of a double-lumen Hickman catheter. Lower incidences of catheter-related Gram-positive sepsis were recorded in patients receiving prophylactic teicoplanin; exit site infection, tunnel infection and catheter-related Gram-positive septicaemia were all reduced. The benefit of prophylactic teicoplanin was observed particularly among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from infected skin sites or from blood cultures taken from Hickman catheters were susceptible to teicoplanin. No adverse reaction was reported in any of the patients receiving prophylaxis. Prophylactic teicoplanin, therefore, may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy, to reduce the early incidence of catheter-related sepsis, particularly during the period of neutropenia following chemotherapy.", "Forty-five children with oncologic or hematologic disorders requiring tunneled central venous catheters (TCVC) for the administration of immunosuppressive therapy were randomized to receive either 10 U/mL heparin (H) (24 patients) or a solution of 10 U/mL H and 25 micrograms/mL vancomycin (H-V) (21 patients) for all catheter flushes. Episodes of fever or suspected sepsis were evaluated to determine whether the addition of vancomycin to the flush solution would alter the incidence of symptomatic bacteremia attributed to luminal colonization of TCVC with vancomycin-susceptible bacteria. Patients were enrolled for 247 +/- 150 days, accounting for a total of 11,095 days of catheter use. Bacteremia attributed to luminal colonization with vancomycin-susceptible organisms occurred in five patients (six infections) receiving H alone compared with zero patients receiving H-V (P = .035). The time to the first episode of bacteremia with vancomycin-susceptible organisms, analyzed by Kaplan-Meier survival curves, was significantly longer in patients receiving H-V (P = .04). There were no differences in the incidence of other infections including bacteremia attributed to luminal colonization with vancomycin-resistant organisms, other bacteremias (including those arising from the catheter exit site), exit-site cellulitis, or fungal infections. No organisms resistant to vancomycin were identified. Vancomycin could not be detected in the peripheral blood of patients receiving vancomycin in the flush solution. No vancomycin-related toxicities were noted. We conclude that the use of an H-V flush solution in immunocompromised patients with TCVC can decrease the frequency of bacteremia attributed to luminal colonization with vancomycin-susceptible bacteria.", "A prospective, randomized, open study comparing two doses of teicoplanin with no therapy administered at the time of insertion of a central venous catheter was performed in patients with hematological malignancies and in patients scheduled to undergo allogeneic or autologous stem cell transplantation. The study was designed as a group sequential study. At predetermined intervals statistical analysis was performed for the main efficacy variable, which was the number of days to treatment failure. Sixty-five patients were randomized. Three patients were judged to be not evaluable. Baseline characteristics were identical in the two groups. No differences were found in overall infections, bacteremias, gram-positive infections, or local infections between the teicoplanin and control groups. Teicoplanin given at the time of insertion of central venous catheters did not reduce the risk of bacteremias or other line-associated infections.", "In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer, we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter \"flush solution.\" In a prospective, placebo-controlled, double-blinded, randomized trial, 69 children with different types of malignancies were studied. The central venous catheters in these children were flushed with either the standard solution (normal saline + 100 U/ml of heparin) or the study solution (25 microgram/ml of both amikacin and vancomycin added to the standard solution). At the conclusion of the study, 64 children with a total of 67 indwelling central venous lines were assessable. The total catheter days on study were 20,700 days, with a median of 323 catheter days per patient. We documented 10 events of catheter-related infections (0.49 events/1,000 catheter days at risk). Five of these events were catheter-related sepsis (0.24 sepses/1,000 catheter days): two were fungal and three were bacterial. Due to the low incidence of catheter-related sepsis in this study, no statement regarding the prophylactic use of antibiotics could be made. The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in handling these catheters. Staff education is essential, and probably the most effective factor in preventing catheter-related sepsis.", "We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms (VSO) in cancer patients with a tunneled central venous catheter (CVC). Eighty-three patients who had a single lumen CVC were randomized to use a heparin solution (25 U/ml) for daily catheter flush with (HepVan) or without (Hep) vancomycin, 25 mcg/ml. Febrile episodes were recorded, and central and peripheral blood cultures were drawn before beginning antibiotic therapy. Patients participated in follow-up to 16,677 catheter days (8,666 Hep and 8,011 HepVan), and 143 febrile episodes were recorded (82 Hep and 61 HepVan). Forty-four episodes of bacteremia occurred, 23 of them due to VSO (16 occurred in the Hep group and 7 in the HepVan group (P = 0.19). VSO bacteremia occurred in 14 neutropenic (absolute neutrophil count < 500 x 10(9)/l) episodes (7 Hep vs. 7 HepVan) and in 9 non-neutropenic episodes (9 Hep vs. O HepVan; P = 0.013). Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients, supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients.", "Infections associated with double-lumen central venous catheters (CVCs) in patients undergoing BMT are presented. We prospectively studied infections occurring with 46 CVCs in 40 patients with malignancies during and up to 30 days after BMT. We randomised patients with insertions of CVCs to receive either a short course of vancomycin 500 mg x 3 peri-operatively (16 CVCs) or no VCM (11 CVCs). Six per cent of CVCs in the group with vancomycin prophylaxis became infected with Gram positive microorganisms compared with 55% in the control group (P < 0.05). Next, 19 patients with CVCs were all given prophylaxis, so finally 35 patients were given vancomycin compared with 11 patients with no vancomycin. In a total of 11 CVC-related infections, 79% of the microbiological isolates were staphylococci, all of which were sensitive to vancomycin. Vancomycin prophylaxis reduced the number of infected CVCs to 11% compared with 45% (P < 0.05) and bacteraemias to 6% compared with 45% (P < 0.01). All infections responded to antibiotic treatment. Prophylactic short-duration vancomycin during insertion of CVCs may reduce the incidence of line-associated infections and Gram positive bacteraemias in patients undergoing BMT.", "To assess whether vancomycin administration at the time of central venous catheter insertion would prevent catheter-related sepsis (CRS) in immunocompromised patients, 98 cancer patients were entered into a randomized placebo-controlled trial. Patients were stratified according to whether they were having therapy for acute leukaemia or undergoing bone-marrow transplantation (group A) or required chemotherapy for a solid tumour (group B). Eligible patients were randomized to receive either 500 mg vancomycin in 250 ml of 0.9% saline prior to catheter insertion followed by a further 500 mg infused via the established catheter, or the same regimen with 0.9% saline alone. In group A, there were 32 instances of CRS occurring in 20 of the 35 evaluable catheters (57%). Six catheters were removed because of CRS. No significant difference was found in the incidence of CRS between the two arms. Of the 37 evaluable catheters in group B, CRS occurred in 6 (16%), and none of the catheters required removal because of CRS. Again, no significant differences were found in the incidence of CRS between the patients given vancomycin or placebo. These findings indicate that the incidence of CRS is greater in patients who have more severe and prolonged immunosuppression and that vancomycin prophylaxis fails to reduce CRS in patients undergoing chemotherapy for malignant disease." ]

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[ "Ovarian suppression induced with Buserelin or danazol in the management of endometriosis: a randomized, comparative study.", "Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study.", "Medical treatment of endometriosis: a comparative trial.", "Gestrinone versus danazol in the treatment of endometriosis.", "Buserelin versus danazol in the treatment of endometriosis-associated infertility.", "Metabolic changes during medical treatment of endometriosis: nafarelin acetate versus danazol.", "An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team.", "A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis.", "Updating the clinical experience in endometriosis--the European perspective.", "Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study.", "Buserelin acetate versus expectant management in the treatment of infertility associated with minimal or mild endometriosis: a randomized clinical trial.", "Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis.", "A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis.", "Successful treatment of asymptomatic endometriosis: does it benefit infertile women?", "Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial.", "Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial.", "Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study.", "Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. The Nafarelin European Endometriosis Trial Group (NEET).", "Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study.", "Effects of triptorelin versus placebo on the symptoms of endometriosis." ]

[ "The effectiveness of Buserelin (Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) (0.2 mg subcutaneously [SC] or 1.2 mg intranasally [IN] per day) and danazol (800 mg per day) in inducing ovarian suppression for the management of endometriosis was compared in a prospective randomized study. During 6 months of treatment, peripheral follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were suppressed to a similar degree in both groups. Symptomatic improvement and laparoscopically assessed regression of endometriotic lesions also were comparable. After treatment, 8 of 18 infertile women treated with Buserelin and 5 of 8 treated with danazol conceived. General and hypoestrogenic side effects were similar in both groups, while androgenic and anabolic were more frequent with danazol. High density lipoprotein (HDL)-cholesterol increased in the Buserelin and decreased in the danazol group. The study indicates that at the dose tested, buserelin and danazol induce a similar degree of ovarian suppression resulting in a comparable clinical improvement and regression of endometriotic lesions.", "We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis.", "In a comparison of danazol, and mestranol with norethynodrel (Enavid, Searle) in the treatment of endometriosis danazol was shown to be superior. Danazol is however relatively ineffective when large tumours or extensive adhesions are present and such patients will usually need a surgical operation. Women who have completed their families and who have severe symptoms will be better treated by hysterectomy. Treatment with danazol is indicated for young women with mild or moderate endometriosis. Danazol treatment may also be given postoperatively after conservative operations.", "Thirty-nine infertile patients with laparoscopic diagnosis of endometriosis were allocated randomly to treatment with gestrinone 2.5 mg twice weekly (20 patients) or danazol 600 mg/day (19 patients) for 6 months. If amenorrhea was not obtained after 1 month of treatment, the gestrinone dose was increased to 2.5 mg three times a week (7 patients) and the danazol dose to 800 mg/day (2 patients). One month after the end of the treatment, a repeat laparoscopy was performed only in the women who agreed (7 of the gestrinone treated group, 9 of the danazol group). All of the patients were followed for at least 12 months after the end of the treatment, during which time they attempted to conceive. There was a marked improvement of pain symptoms during the treatment in the patients of both groups. The repeat laparoscopy did not reveal significant differences between the two groups in the reduction of the disease extent. Eighteen months after treatment suspension, the cumulative pregnancy rate was 33% in the patients treated with gestrinone and 40% in those treated with danazol. Pain symptoms recurred during the follow-up in 57% of the gestrinone and 53% of the danazol group. The side effects were more frequent and severe with the danazol treatment, whereas those caused by gestrinone were mostly weight gain and acne. The results of this study suggest that gestrinone is as effective as danazol in the treatment of infertility associated with endometriosis and is better tolerated.", "A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.", "In this double-blind study of changes in plasma lipid and lipoprotein concentrations during 6-month medical treatment of endometriosis, 53 patients were randomly assigned to one of four treatment schedules: danazol, 800 mg/day (n = 10); danazol, 600 mg/day (n = 8); intranasal nafarelin acetate, 800 micrograms/day (n = 10); or intranasal nafarelin acetate, 400 micrograms/day (n = 25). Plasma levels of triglycerides, cholesterol, and low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein cholesterol fractions were obtained before, during, and 1 month after treatment. High-density lipoprotein2 and high-density lipoprotein3 cholesterol concentrations were measured in selected patients. Body weight was also followed. The drugs were equally effective in achieving symptomatic relief and laparoscopically demonstrated resolution of endometriosis but differed significantly in their effects on lipid concentrations. Nafarelin acetate had no adverse effects on serum lipoprotein concentrations, whereas danazol significantly decreased high-density lipoprotein cholesterol (p less than 0.01), as well as the high-density lipoprotein2 subfraction (p less than 0.05), and increased low-density lipoprotein cholesterol (p less than 0.01). Danazol significantly increased body weight (p less than 0.01), whereas nafarelin did not.", "To compare the efficacy and safety of goserelin depot and danazol for endometriosis.\n Open, randomized comparative trial.\n Multicenter European academic clinical institutions.\n A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy.\n A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks.\n Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures.\n There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol.\n The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d.", "To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis.\n Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients).\n Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test).\n Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.", "In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group.", "To determine the efficacy of medroxyprogesterone acetate (MPA), 50 mg/d for 3 months, in treating endometriosis, with a follow-up of 6 months.\n Prospective, randomized, double-blind, placebo-controlled trial.\n Academic infertility unit in a teaching hospital.\n One hundred infertile women found to have endometriosis at laparoscopy, with 50 recruited to each treatment arm.\n Laparoscopy within 3 months of finishing therapy.\n Initial and second-look laparoscopy for revised American Fertility Society stages and scores, pregnancies achieved, effects on well-being via symptomatic improvement, and side effects.\n Whether initially high or low, both MPA and placebo therapy achieved similar statistically significant reductions in stages and scores at second-look laparoscopy. MPA was rated more effective in improving overall well-being. Side effects were minimal in both groups (10% MPA; 2% placebo). Six pregnancies occurred without other endometriosis therapy being instituted in the placebo group (3 during therapy), and one with MPA (0 during therapy).\n Both MPA and placebo appear equally and significantly effective in treating endometriosis over a 3-month period, as judged by comparative laparoscopy. Therefore, not only must the use of MPA at 50 mg/d over 3 months be questioned, but the performance of placebo also suggests the need to review whether therapy should be instituted at all as well as the present concept that endometriosis is frequently a spontaneously progressive phenomenon.", "We performed a randomized clinical trial to evaluate the efficacy of intranasal 400 micrograms buserelin three times daily for 6 months versus expectant management in the treatment of infertile women with pelvic endometriosis stage I or II of the revised American Fertility Society classification.\n Seventy-one consecutive patients (mean age 32 years) were studied at the First Department of Obstetrics and Gynecology, University of Milan, and the Department of Obstetrics and Gynecology, Ospedali Riuniti, Bergamo, between February 1988 and June 1989. Thirty-five women were randomly allocated to buserelin treatment and 36 to expectant management. The baseline distribution of subjects for age, disease stage, and reproductive history was similar in the two groups. All patients were followed regularly; median follow-up was 17 months in the buserelin group and 18 months in the women given expectant management. If pregnancy did not occur within 12 months of randomization, cycles were monitored by ultrasonography and hormone measurements, and when abnormalities were detected clomiphene citrate and human chorionic gonadotropin were administered.\n A total of 17 pregnancies were observed both in the buserelin-treated patients and in the expectant management group. The 1- and 2-year actuarial overall pregnancy rates were similar in the two groups, 30% and 61% in the former and 37% and 61% in the latter group, respectively. Spontaneous abortion occurred in five of the 17 pregnancies in the women treated with buserelin and in one of the 17 in those managed expectantly; this difference was, however, not statistically significant (chi 1(2) adjusted for disease stage and use of clomiphene citrate and human chorionic gonadotropin treatment = 3.01, p = 0.08). No fetal death or stillbirth was observed.\n Our findings suggest that treatment with gonadotropin-releasing hormone agonists is unlikely to have a marked influence on the reproductive outcome of infertile women with minimal or mild endometriosis.", "Danazol (200 mg three times a day) and medroxyprogesterone acetate (MPA, 100 mg a day) were compared with placebo in the treatment of infertility of patients with endometriosis. Twenty-seven patients had medical therapy alone for 6 months, and 22 patients received it after conservative surgery. The clinical characteristics of the patients in the danazol group (n = 18), the MPA group (n = 17), and the placebo group (n = 14) were comparable to each other. The follow-up time was 30 months. The cumulative pregnancy rates, 33% in the danazol group (n = 6), 42% in the MPA group (n = 7), and 46% in the placebo group (n = 6), did not differ significantly from each other. The time to pregnancy after the start of therapy was 17.7 +/- 8.4 (standard deviation [SD]) months in the danazol group, 18.0 +/- 9.0 months in the MPA group and 10.0 +/- 5.8 months in the placebo group with no significant difference between the groups. The abortion rate was 26%, and there was no significant difference among the groups. Cox multivariant analysis did reveal ovarian endometriosis a prognostically significant negative indicator as regards fecundation in endometriosis (P less than 0.05). In summary, correction of infertility alone does not appear to be an indication for the use of danazol or MPA in the treatment of endometriosis, and ovarian endometriotic lesions but not peritoneal ones do make a worse prognosis as regards fecundation in endometriosis.", "To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post-operative hormonal therapy compared with women treated with surgery only. Pregnancy rates and time to conception in women wanting children were also evaluated.\n A multicentre, prospective, randomised controlled study.\n Nineteen Italian academic departments and teaching hospitals specialising in reparative and reconstructive surgery.\n A total of 269 women undergoing conservative surgery for mild to severe symptomatic endometriosis.\n After surgery the women were assigned to treatment with subcutaneous goserelin depot injections for six months or to expectant management. Dysmenorrhoea, deep dyspareunia, nonmenstrual pain and general discomfort were graded according to a verbal rating scale from 0 (absent) to 3 (severe) and the scores summed to give a total symptoms score. Only patients with at least one preoperative moderate or severe symptom were enrolled. The women were evaluated regularly for two years.\n Post-operative pain recurrences (total symptoms scores > or = 5), time to recurrence, pregnancy rates and time to conception in the two study groups.\n At one- and two-year follow up visits, 14/107 (13.1%) and 19/81 (23.5%) patients had moderate or severe symptoms recurrence in the goserelin group compared with, respectively, 22/103 (21.4%) and 27/74 (36.5%) in the expectant management group (P = 0.143 at 1 year and 0.082 at 2 years). Time to symptoms recurrence was significantly longer in the goserelin group according to survival analysis (Wilcoxon test, P = 0.041). Among women wanting children, few conceptions occurred in both the goserelin (8/69, 11.6%) and the expectant management group (14/76, 18.4%). There was no significant difference at survival analysis (Wilcoxon test, P = 0.427).\n Post-operative treatment with goserelin significantly prolonged the pain-free interval after conservative surgery for symptomatic endometriosis and did not influence reproductive prognosis.", "The relation between asymptomatic endometriosis and infertility was investigated in a randomised double blind placebo controlled trial of the impact of treating the endometriosis with gestrinone. The 12 month cumulative conception rate in those patients treated with gestrinone was 25% (5/20) and in those given placebo 24% (4/17). These same patients were divided into those in whom no visible endometriosis was present at the second laparoscopy and those in whom residual disease was present and the 12 month cumulative conception rates were 25% (4/16) and 30% (6/20) respectively. None of these rates differed significantly, and they compared with a rate of 23% (6/26) in a control group of patients with unexplained infertility. Those patients in whom the disease was eliminated did not return to normal fertility, though all other causes of infertility were excluded. This study failed to show any impact of treatment or the absence or presence of asymptomatic endometriosis on future fertility compared with patients with unexplained infertility. The findings therefore question any causal role of the disease in infertility.", "In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory.\n A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence.\n During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography.\n This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV.", "Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis.\n Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society, revised, classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions. Patients were assigned according to a randomization list to nasal nafarelin, 400 micrograms/day (36 subjects) or placebo nasal spray (39 subjects) for 3 months. Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale.\n No marked differences in pain scores emerged among women allocated to different treatments. The mean reduction of the multidimensional score was 3.6 and 4.0, respectively, in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9. These differences were not statistically significant. Within 1 year from randomization, of the 36 women allocated to nafarelin and the 39 allocated to placebo, seven (19%) and seven (18%), respectively, became pregnant.\n This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis.", "The effect of treatment with danazol was evaluated with respect to expectant management after laparoscopic conservative surgery. All patients conservatively operated at laparoscopy for stage III-IV endometriosis from July 1994 to October 1996 were requested to enter the study. Patients who underwent surgery for recurrent endometriosis were excluded from the study, as well as patients who had taken hormonal therapies before laparoscopy. Informed consent was obtained from 77 women who were randomized after surgery to treatment with danazol 600 mg daily for 3 months (n = 36) or to expectant management (n = 41). All patients were regularly followed up every 6 months for evaluation of fertility, recurrence of pain symptoms and disease. During the follow-up, six (55%) of the 11 infertile women allocated to danazol and eight (50%) of the 16 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during follow-up in seven (23%) of the 31 women with pelvic pain allocated to the danazol group and nine (31%) of the 29 allocated to no treatment; the respective cumulative pain recurrence rates at 12 months were 26 and 34% (log rank test, not significant). Three women (8.3%) treated with danazol and six (15%) who received no treatment had disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography (not significant). Our results do not demonstrate a significant advantage of 3 month danazol therapy after laparoscopic surgery for stage III-IV endometriosis with respect to postoperative expectant management.", "To compare the efficacy and safety of nafarelin and danazol for endometriosis.\n Randomized, double-blind, double-dummy.\n Multiple European institutions.\n In total, 307 patients with laparoscopically diagnosed endometriosis received nafarelin (n = 206) or danazol (n = 101); 263 (171 nafarelin, 92 danazol) were analyzed for efficacy.\n Intranasal nafarelin 200 micrograms two times a day or oral danazol 200 mg three times a day were administered for 6 months.\n Efficacy assessments were based on preadmission and end-of-treatment laparoscopic scores and subjective symptom scores at admission, end of treatment, 1, 3, 6, and 12 months after treatment. Safety was evaluated by adverse events and clinical laboratory tests.\n In each group, endometriosis growth and symptoms significantly improved during treatment (P less than 0.001). After treatment, symptoms returned in each group, but severity was less than at admission at all time points (P less than or equal to 0.016). Mean body weight increased in the danazol-treated group (P less than 0.001), serum glutamic oxaloacetic transaminase increased in both groups (P less than 0.001 for both) but significantly more in danazol users (P less than 0.002), and more nafarelin recipients had hot flushes (P less than 0.001).\n Nafarelin and danazol were equally effective in reducing endometriosis growth and symptoms during treatment and in preventing the return of symptoms during 12-month follow-up.", "To compare the efficacy of Dienogest versus Decapeptyl at 3.75 mg as consolidation therapy for surgery in the treatment of endometriosis.\n Multicenter, open, randomized, parallel-group clinical trial.\n Volunteer patients in an academic research environment.\n Women with grade 2, 3, and 4 (</=70) endometriosis at initial laparoscopy.\n We provided 16 weeks of treatment with Dienogest, 1 mg tablet daily; or with Decapeptyl, 3.75 mg IM injection every 4 weeks. Main Outcome Measure(S): A change in the patient's Revised American Fertility Society score at the post-treatment laparoscopy.\n From June 1994 to July 1998, 142 patients were enrolled in the trial. After exclusion for major protocol deviations, 59 patients were included in the Dienogest group and 61 in the Decapeptyl group. This study group was comparable to the first inclusion group. The patient demographic and clinical characteristics, median duration of endometriosis, Revised American Fertility Society scores, and Visual Analogic Squale (VAS) scores were comparable in both groups. Statistical analysis of efficacy was not significantly different between the two groups. Adverse events were reported by 87.7% of patients in the Dienogest group and 85.1% in the Decapeptyl group. Neither treatment affected patient body weight or vital signs.\n Dienogest is as effective as Decapeptyl for consolidation therapy after surgery for the treatment of endometriosis. The safety profile of dienogest differed from Decapeptyl (3.75 mg). Dienogest constitutes a new therapeutic alternative to the GnRH analogues.", "To compare the effect of a GnRH-agonist, triptorelin, versus placebo on the symptoms of endometriosis.\n A prospective, randomized, double-blind study of 6 months of treatment followed by 12 months of follow-up.\n Departments of Obstetrics and Gynecology at two universities and one general hospital.\n Forty-nine women with symptoms of laparoscopically verified endometriosis.\n Triptorelin depot or placebo was given every 4 weeks. Clinical evaluation, including the Duration Intensity Behavior Scale and Visual Analogue Scale for pain, was performed before the injections and up to 12 months after treatment. A control laparoscopy was performed 4-6 weeks after the last injection.\n Quantitation of pain.\n Twenty-four patients had active treatment and 25 received placebo. Pain symptoms according to both scales were significantly more reduced after 2 months of triptorelin treatment compared to placebo. The extent of endometriotic lesions was reduced 50% during triptorelin treatment and increased 17% during placebo. The average area of endometriotic lesions was reduced 45% during triptorelin treatment but was unchanged during placebo. Side effects, mainly hot flushes, were experienced by 80% of the actively treated group but also by 33% of patients in the placebo group. Because of recurrent symptoms, only five patients could be observed for 12 months after completion of treatment.\n Triptorelin reduces endometriotic lesions and pain to a significantly higher degree than placebo." ]

[ "1155439", "9809909" ]

[ "Some epidemiologic features of motorcycle collision injuries. I. Introduction, methods and factors associated with incidence.", "Effect of motorcycle rider education on changes in risk behaviours and motorcycle-related injuries in rural Thailand." ]

[ "Using official police reports and hospital admission and emergency room medical records, 1273 persons with confirmed medically treated motorcycle injury were identified in Sacramento County, California, during 1970. Less than 39% of all injured motorcyclists were identified in this study using only official police reports. The annual incidence rate was highest for 18-year-old male drivers. In addition to age of driver, risk of injury was associated with drivers of short stature (less than 173 cm) operating an intermediate or larger size motorcycle. Risk of injury was higher for drivers with training than for those without training or those who operated their motorcycles frequently regardless of type of use. Risk of injury was not related to make of motorcycle but was related to engine size. Two-thirds of the injury-producing collisions involved a motorcycle and a second motor vehicle. Motorcycle collisions occurred most fre quently during the afternoon and early evening hours and during the summer months, but peaks in incidence of collisions occurred during weeks which included a holiday.", "A community-based programme for motorcycle rider education was provided for motorcyclists in all villages of 3 randomly selected subdistricts in Mae Sot District, Tak Province, northern Thailand, between January and March 1995. To determine the extent of changes in risk-taking behaviours, we conducted an interview survey of motorcyclists in 3 villages selected by systematic sampling from the 3 intervention subdistricts and in 3 control (without intervention) villages for comparison in March 1997, 2 years after the programme. Motorcyclists in the intervention villages (69.7%) were significantly more likely to have valid licences than those in the control villages (46.5%). The proportion of motorcyclists who always or often wore helmets was significantly greater in the intervention sample (46.0%) than in the control sample (20.5%). In 1994, the annual incidence rate of motorcycle-related injuries was slightly higher in the intervention areas than in the control areas Following the education programme, the injury rates for 1995 and 1996 were significantly lower in the intervention than in the control population. The annual number and rate of fatal motorcycle injuries decreased after the intervention although there was no significant difference between the two populations. Motorcycle rider education may be a promising intervention for prevention of motorcycle-related injuries in rural areas where road safety measures, particularly enforcement activities, are commonly limited." ]

[ "19835717" ]

[ "Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel." ]

[ "This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol.\n This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years.\n Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG.\n A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC." ]

[ "18927130", "18554591", "19409544" ]

[ "A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program.", "Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study.", "A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of intracytoplasmic sperm injection cycles." ]

[ "The potentially damaging effect of free O(2) radicals to cultured embryos may be reduced by adding scavengers to the culture media or by reducing the incubator O(2) levels. However, lowering the O(2) in the culture environment can be expensive, troublesome and may not be justifiable. The objective of this study was to evaluate the effect of lowered incubator O(2) tension on live birth rates in a predominately Day 5 embryo transfer program.\n Two hundred and thirty first-cycle women undergoing routine IVF or ICSI with ejaculated sperm were randomized in a prospective clinical trial and stratified for patient age and physician. Embryos of patients were randomly assigned for culture in either a 21% O(2) (atmospheric) or 5% O(2) (reduced) environment. Clinical endpoints monitored were rates of implantation, clinical pregnancy, live birth and blastocyst cryopreservation.\n Embryos cultured in a 5% O(2) environment consistently resulted in higher rates of live birth implantation (106/247, 42.9% versus 82/267, 30.7%; difference of 12.2% with 95% confidence interval (CI) of 3.9-20.3, P = 0.005) and live births (66/115, 57.4% versus 49/115, 42.6%; difference of 14.8% with 95% CI of 1.9-27.0, P = 0.043) when compared with rates among women whose embryos were cultured in an atmospheric O(2) environment.\n The overall increase in live births demonstrated by this study indicates that the effort and expense to culture embryos in a low-O(2) environment is justified. The study was registered at clinicaltrials.gov. NCT00708487.", "To investigate birth rates with two oxygen (O(2)) concentrations in blastocyst culture.\n Randomized trial.\n Private in vitro fertilization (IVF) clinic.\n Six hundred women undergoing IVF.\n Blastocyst culture in atmospheres with either 6% carbon dioxide (CO(2)) in air, the equivalent to 19% O(2), a two-gas system; or 5% O(2), 6% CO(2), and 90% nitrogen (N(2)), a three-gas system.\n Birth rate.\n The inclusion criterion for blastocyst culture (at least five fertilized oocytes) was fulfilled in 396 women, randomized to 197 cultures with the three-gas system and 199 cultures with the two-gas system. The outcome with the three-gas system compared with the two-gas system showed a statistically significantly increased blastocyst rate (47.8% vs. 42.1%), mean number of blastocysts (3.8 vs. 3.3), and number of cryopreserved blastocysts (1.7 vs. 1.1). The mean number of transferred blastocysts was 1.2 versus 1.3. Culture with the three-gas system increased the relative birth rate by 10% compared with the two-gas system (42% vs. 32%, respectively), a statistically significant difference. The overall twin rate was 4.8%.\n Blastocyst culture with low-oxygen (5%) versus high-oxygen (19%) concentration yielded a better blastocyst outcome and a marked improvement in birth rate. Generation of cytotoxic reactive oxygen species with prolonged embryo culture might deteriorate blastocyst viability.", "To assess whether the embryo cultivation at different oxygen tensions had any effect on intracytoplasmic sperm injection (ICSI) outcome.\n Prospective randomized trial.\n University clinical center.\n Women undergoing ICSI (n = 647).\n Culturing of embryos, either at 6% CO(2), 5% O(2), 89% N(2), or at 6% CO(2) in air.\n The primary outcome was ongoing pregnancy rates (PR). Secondary outcomes: cumulative PRs, implantation, and embryo quality, for both treatment groups and clinical outcomes for subgroups (optimal cycles, poor responders, older women).\n Although low oxygen resulted in a higher proportion of good day 2 embryos (0.547 +/- 0.021 vs. 0.39 +/- 0.019) and optimal blastocysts (0.162 +/- 0.199 vs. 0.083 +/- 0.128), the ongoing PRs (31.6% vs. 27.1%) and implantation rates (28.8% vs. 25.2%) were similar in both oxygen groups. Low oxygen caused a higher cumulative PR (38% vs. 28.3%) in the main group and a higher PR in the poor responder subgroup (23% vs. 9.8%) with embryo transfers performed mostly on day 3.\n The use of reduced oxygen in IVF is reasonable, irrespective of the duration of embryo culture. It improves embryo development and cumulative PR and is also recommended in poor responding cycles.\n Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved." ]

[ "7508675", "1381102", "10711911", "10484947", "7694306", "8834417", "7691017", "11120421", "10693159", "1375801", "7542829", "11777998", "7683702" ]

[ "Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations.", "Risperidone: clinical safety and efficacy in schizophrenia.", "Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia.", "Risperidone in treatment-refractory schizophrenia.", "Double-blind comparison of risperidone and haloperidol in schizophrenic and schizoaffective psychoses.", "Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients.", "Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: a parallel group double-blind comparative trial.", "Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial.", "Effects of atypical neuroleptics on sustained attention deficits in schizophrenia: a trial of risperidone versus haloperidol.", "Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study.", "Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.", "A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia.", "A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients." ]

[ "Risperidone (RIS), a new neuroleptic with 5-HT2- and dopamine D2 receptor-blocking properties, was compared with perphenazine (PER) in a double-blind, multicentre, parallel-group study in 107 chronic schizophrenics with acute exacerbation. RIS 5-15 mg or PER 16-48 mg daily was given for 8 weeks. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression. Seventy-eight patients completed the trial; there was an equal number of dropouts on both drugs. The mean daily dose at endpoint was 8.5 mg RIS and 28 mg PER. The reduction in total PANSS score to endpoint did not differ significantly, although there was a tendency in favour of RIS. The number of patients with predominantly negative symptoms who showed at least 20% reduction in total PANSS score was significantly larger in the RIS group. Furthermore, the number of patients showing at least 20% reduction in Brief Psychiatric Rating Scale (BPRS) score (BPRS being a subscale of PANSS) was significantly larger in the RIS group. The hostility cluster of BPRS improved more on RIS than on PER in the endpoint analysis. The overall prevalence of side effects was fairly similar in the two groups.", "Risperidone represents a unique pharmacology of potent antagonism of both serotonin and dopamine receptors. In a randomized, parallel-group, double-blind trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in acute exacerbation, risperidone showed a quicker onset of antipsychotic activity than did haloperidol. Risperidone treatment was statistically superior to placebo, with a trend toward superiority to haloperidol. Risperidone did not differ from placebo on assessment scales of extrapyramidal side effects, but produced significantly less than did haloperidol. There were no major adverse reactions associated with risperidone use, but it was noted to reduce the signs of tardive dyskinesia. This study suggests that risperidone may offer a superior side-effect profile, and possibly greater efficacy, than a standard neuroleptic such as haloperidol.", "The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia.\n Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment.\n The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test.\n These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.", "The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia.\n Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N = 34) or haloperidol (N = 33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments.\n Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly les observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia.\n Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone.", "A double-blind eight-week study was carried out to compare the efficacy and safety of risperidone in relation to haloperidol. Sixty-two inpatients suffering from acute schizophrenic or schizoaffective psychoses diagnosed according to ICD-9 were treated with risperidone 2-20 mg daily or haloperidol 2-20 mg daily. The mean total BPRS scores were reduced from 45.5 to 32.4 in the risperidone group and from 43.1 to 28.5 in haloperidol group. There were no significant differences between the two treated groups with regard to the total BPRS score and the percentage of remissions achieved. No statistically significant difference was found between the groups in any of the factors or items except guilt feeling (p < 0.02), anxiety (p < 0.005), and factor I--anxiety/depression--(p < 0.02) in favour of haloperidol. Risperidone had the benefit of a lower incidence of extrapyramidal side-effects.", "The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were randomly assigned to receive risperidone (mean dose, 7.4 mg/day), haloperidol (7.6 mg/day), or methotrimeprazine (100 mg/day) for 4 weeks. Clinical improvement, defined a priori as a 20% reduction in total Positive and Negative Syndrome Scale (PANSS) scores at end point, was attained by 81% of the risperidone patients, 60% of the haloperidol patients, and 52% of the methotrimeprazine patients (p < 0.05). The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups. Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients; the difference between haloperidol and methotrimeprazine was not significant. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) were more severe in the haloperidol patients than in the other two groups, but few differences were apparent between risperidone and methotrimeprazine patients. It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients.", "A parallel group double-blind comparative trial was conducted to study the efficacy and safety of risperidone compared with haloperidol. After a one-week wash-out, 35 chronic schizophrenic patients (17 males, 18 females) were randomly assigned to one of two groups for eight weeks of double-blind treatment. The patients' psychopathology was assessed by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinical Global Impression (CGI). Safety assessments included the Extrapyramidal Symptom Rating Scale (ESRS), the UKU Side Effect Rating Scale, vital signs, body weight, ECG and laboratory screening. Thirty-two patients completed the trial: there were 3 dropouts in the risperidone group. The results on the PANSS and CGI indicate that the mean changes from baseline on the total PANSS score and on the total BPRS score were comparable in both treatment groups. The number of patients where a clinical improvement at least 20% reduction in baseline score was also similar in both treatment groups. Risperidone caused less extrapyramidal symptoms and less side effects in UKU scale than haloperidol. No significant ECG changes were induced, no relevant changes in blood pressure or clinical laboratory parameters were observed. This study has demonstrated that the combined serotonin 5-HT2 and dopamine-D2 antagonist risperidone is an antipsychotic as potent as haloperidol. Risperidone causes less extrapyramidal symptoms, and is better tolerated than haloperidol.", "A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication.\n Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men).\n An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication.\n In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.", "To help determine whether sustained attention deficits as measured with the Continuous Performance Test (CPT) are stable vulnerability indicators of schizophrenia, we compared the CPT performance of schizophrenic patients before and after treatment with risperidone or haloperidol. In this double blind trial, 56 schizophrenic patients were randomly assigned to a 12-week regimen of either risperidone or haloperidol, after a 1-week washout period. The patients undertook two sessions of the CPT (undegraded and 25% degraded) twice, one at the end of the washout period and the other at the end of the study. Thirty-eight patients completed the study, 19 in each group. Both groups experienced significant improvements in clinical symptoms, and the risperidone group showed no change in the severity of extrapyramidal symptoms. Despite those improvements, the CPT performance indexes did not change significantly from the beginning to the end of the study. These findings indicate that sustained attention deficits might be stable vulnerability indicators of schizophrenia.", "Forty-four chronic schizophrenic inpatients participated in this multicentre 12-week parallel-group double-blind trial. After a run-in period of 2 weeks and a single-blind placebo wash-out of 1 week, they were randomly assigned to treatment with either the serotonin2 and dopamine-D2 antagonist risperidone or haloperidol. Two patients were excluded from the efficacy analysis. Five patients dropped out in the haloperidol group and 1 in the risperidone group. At the end of the trial, the mean daily dose was 12 mg for risperidone and 10 mg for haloperidol. The risperidone group showed greater improvement on the Positive and Negative Syndrome Scale for Schizophrenia, the Schedule for Affective Disorders and Schizophrenia-change version, and the Nurses' Observation Scale for Inpatient Evaluation. The improvement of negative symptoms was more pronounced in the risperidone group until week 8 of double-blind treatment. The consumption of antiparkinsonian medication was 10 times lower with risperidone. Both drugs were well tolerated and the laboratory, endocrinological and cardiovascular safety parameters were comparable. This study suggests that risperidone is comparable to haloperidol as an antipsychotic, but that it has a safer EPS profile.", "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.", "Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder.\n In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year.\n Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group.\n Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol.", "In a double-blind study, 135 inpatients with a diagnosis of chronic schizophrenia were randomly assigned to 8 weeks of treatment with one of six parallel treatments: risperidone (a new central 5-hydroxytryptamine2 and dopamine D2 antagonist), 2, 6, 10, 16 mg/day; haloperidol, 20 mg/day; or placebo, after a single-blind placebo washout period. Doses were increased in fixed increments up to a fixed maintenance dose reached after 1 week. On the Clinical Global Impression-Severity of Illness and Improvement, all active medications were superior to placebo except for risperidone (2 mg) on the Clinical Global Impression-Improvement. On the total Positive and Negative Syndrome Scale (PANSS) score and positive subscale, superiority to placebo was observed for all treatment groups except for haloperidol and risperidone (2 mg), which tended to be superior to placebo on total PANSS and the positive subscale, respectively. On the PANSS negative subscale, only risperidone (6 mg/day) was significantly better than placebo. Risperidone (6 mg) was superior to haloperidol on the total PANSS, General Psychopathology, and Brief Psychiatric Rating Scale subscales. Although there was a linear increase in parkinsonism with increasing risperidone dosage, there were no statistically significant differences between risperidone (2, 6, and 16 mg/day) and placebo. At doses of 6 to 16 mg, risperidone displayed a marked antidyskinetic effect compared with placebo. This effect was more pronounced in patients with severe dyskinesia. By contrast, haloperidol produced significantly more parkinsonism than placebo and risperidone (2, 6 and 16 mg), with no effect on tardive dyskinesia. These data suggest that risperidone, at the optimal therapeutic dose of 6 mg/day, produced significant improvement in both positive and negative symptoms without an increase in drug-induced parkinsonian symptoms and with a significant beneficial effect on tardive dyskinesia." ]

[ "15743283", "16181164", "17678655", "10768528", "15574110", "19969159" ]

[ "Exercise leads to faster postural reflexes, improved balance and mobility, and fewer falls in older persons with chronic stroke.", "A community-based fitness and mobility exercise program for older adults with chronic stroke: a randomized, controlled trial.", "Circuit class therapy versus individual physiotherapy sessions during inpatient stroke rehabilitation: a controlled trial.", "Task-related circuit training improves performance of locomotor tasks in chronic stroke: a randomized, controlled pilot trial.", "Additional task-related practice improves mobility and upper limb function early after stroke: a randomised controlled trial.", "Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial." ]

[ "To determine the effect of two different community-based group exercise programs on functional balance, mobility, postural reflexes, and falls in older adults with chronic stroke.\n A randomized, clinical trial.\n Community center.\n Sixty-one community-dwelling older adults with chronic stroke.\n Participants were randomly assigned to an agility (n=30) or stretching/weight-shifting (n=31) exercise group. Both groups exercised three times a week for 10 weeks.\n Participants were assessed before, immediately after, and 1 month after the intervention for Berg Balance, Timed Up and Go, step reaction time, Activities-specific Balance Confidence, and Nottingham Health Profile. Testing of standing postural reflexes and induced falls evoked by a translating platform was also performed. In addition, falls in the community were tracked for 1 year from the start of the interventions.\n Although exercise led to improvements in all clinical outcome measures for both groups, the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group. In addition, the agility group experienced fewer induced falls on the platform.\n Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes, functional balance, and mobility and may lead to a reduction of falls in older adults with stroke.", "To examine the effects of a community-based group exercise program for older individuals with chronic stroke.\n Prospective, single-blind, randomized, controlled intervention trial.\n Intervention was community-based. Data collection was performed in a research laboratory located in a rehabilitation hospital.\n Sixty-three older individuals (aged > or = 50) with chronic stroke (poststroke duration > or = 1 year) who were living in the community.\n Participants were randomized into intervention group (n=32) or control group (n=31). The intervention group underwent a fitness and mobility exercise (FAME) program designed to improve cardiorespiratory fitness, mobility, leg muscle strength, balance, and hip bone mineral density (BMD) (1-hour sessions, three sessions/week, for 19 weeks). The control group underwent a seated upper extremity program.\n Cardiorespiratory fitness (maximal oxygen consumption), mobility (6-minute walk test), leg muscle strength (isometric knee extension), balance (Berg Balance Scale), activity and participation (Physical Activity Scale for Individuals with Physical Disabilities), and femoral neck BMD (using dual-energy x-ray absorptiometry).\n The intervention group had significantly more gains in cardiorespiratory fitness, mobility, and paretic leg muscle strength than controls. Femoral neck BMD of the paretic leg was maintained in the intervention group, whereas a significant decline of the same occurred in controls. There was no significant time-by-group interaction for balance, activity and participation, nonparetic leg muscle strength, or nonparetic femoral neck BMD.\n The FAME program is feasible and beneficial for improving some of the secondary complications resulting from physical inactivity in older adults living with stroke. It may serve as a good model of a community-based fitness program for preventing secondary diseases in older adults living with chronic conditions.", "To compare the effectiveness of circuit class therapy and individual physiotherapy (PT) sessions in improving walking ability and functional balance for people recovering from stroke.\n Nonrandomized, single-blind controlled trial.\n Medical rehabilitation ward of a rehabilitation hospital.\n Sixty-eight persons receiving inpatient rehabilitation after a stroke.\n Subjects received group circuit class therapy or individual treatment sessions as the sole method of PT service delivery for the duration of their inpatient stay.\n Five-meter walk test (5MWT), two-minute walk test (2MWT), and the Berg Balance Scale (BBS) measured 4 weeks after admission. Secondary outcome measures included the Iowa Level of Assistance Scale, Motor Assessment Scale upper-limb items, and patient satisfaction. Measures were taken on admission and 4 weeks later.\n Subjects in both groups showed significant improvements between admission and week 4 in all primary outcome measures. There were no significant between group differences in the primary outcome measures at week 4 (5MWT mean difference, .07m/s; 2MWT mean difference, 1.8m; BBS mean difference, 3.9 points). A significantly higher proportion of subjects in the circuit class therapy group were able to walk independently at discharge (P=.01) and were satisfied with the amount of therapy received (P=.007).\n Circuit class therapy appeared as effective as individual PT sessions for this sample of subjects receiving inpatient rehabilitation poststroke. Favorable results for circuit classes in terms of increased walking independence and patient satisfaction suggest this model of service delivery warrants further investigation.", "To evaluate the immediate and retention effects of a 4-week training program on the performance of locomotor-related tasks in chronic stroke.\n Randomized, controlled pilot study with 2-month follow-up.\n Rehabilitation center.\n A convenience sample consisting of 12 chronic stroke subjects was used. Subjects were randomly assigned to the experimental or the control group. Three subjects withdrew from the study.\n Both experimental and control groups participated in exercise classes three times a week for 4 weeks. The exercise class for the experimental group focused on strengthening the affected lower limb and practicing functional tasks involving the lower limbs, while the control group practiced upper-limb tasks.\n Lower-limb function was evaluated by measuring walking speed and endurance, peak vertical ground reaction force through the affected foot during sit-to-stand, and the step test.\n The experimental group demonstrated significant immediate and retained (2-month follow-up) improvement (p < or = .05) compared with the control group in walking speed and endurance, force production through the affected leg during sit-to-stand, and the number of repetitions of the step test.\n The pilot study provides evidence for the efficacy of a task-related circuit class at improving locomotor function in chronic stroke.", "The purpose of this study was to investigate whether additional practice of either upper limb or mobility tasks improved functional outcome during inpatient stroke rehabilitation. This prospective, randomised, single blind clinical trial recruited 30 stroke subjects into either an Upper Limb or a Mobility Group. All subjects received their usual rehabilitation and an additional session of task-related practice using a circuit class format. Independent assessors, blinded to group allocation, tested all subjects. Outcome measures used were three items of the Jebsen Taylor Hand Function Test (JTHFT), two arm items of the Motor Assessment Scale (MAS), and three mobility measures, the Timed Up and Go Test (TUGT), Step Test, and Six Minute Walk Test (6MWT). Both groups improved significantly between pre- and post-tests on all of the mobility measures, however only the Upper Limb Group made a significant improvement on the JTHFT and MAS upper arm items. Following four weeks training, the Mobility Group had better locomotor ability than the Upper Limb Group (between-group differences in the 6MWT of 116.4 m, 95% CI 31.4 to 201.3 m, Step Test 2.6 repetitions, 95% CI -1.0 to 6.2 repetitions, and TUGT -7.6 sec, 95% CI -15.5 to 0.2 sec). The JTHFT dexterity scores in the Upper Limb Group were 6.5 sec (95% CI -7.4 to 20.4 sec) faster than the Mobility Group. Our findings support the use of additional task-related practice during inpatient stroke rehabilitation. The circuit class format was a practical and effective means to provide supervised additional practice that led to significant and meaningful functional gains.", "Mudge S, Barber PA, Stott NS. Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial.\n To determine whether circuit-based rehabilitation would increase the amount and rate that individuals with stroke walk in their usual environments.\n Single-blind randomized controlled trial.\n Rehabilitation clinic.\n Sixty participants with a residual gait deficit at least 6 months after stroke originally enrolled in the study. Two withdrew in the initial phase, leaving 58 participants (median age, 71.5y; range, 39.0-89.0y) who were randomized to the 2 intervention groups.\n The exercise group had 12 sessions of clinic-based rehabilitation delivered in a circuit class designed to improve walking. The control group received a comparable duration of group social and educational classes.\n Usual walking performance was assessed using the StepWatch Activity Monitor. Clinical tests were gait speed (timed 10-meter walk) and endurance (six-minute walk test [6MWT]), confidence (Activities-Based Confidence Scale), self-reported mobility (Rivermead Mobility Index [RMI]), and self-reported physical activity (Physical Activity and Disability Scale).\n Intention-to-treat analysis revealed that the exercise group showed a significantly greater distance for the 6MWT than the control group immediately after the intervention (P=.030) but that this effect was not retained 3 months later. There were no changes in the StepWatch measures of usual walking performance for either group. The exercise and control groups had significantly different gait speed (P=.038) and scores on the RMI (P=.025) at the 3-month follow-up. These differences represented a greater decline in the control group compared with the exercise group for both outcome measures.\n Circuit-based rehabilitation leads to improvements in gait endurance but does not change the amount or rate of walking performance in usual environments. Clinical gains made by the exercise group were lost 3 months later. Future studies should consider whether rehabilitation needs to occur in usual environments to improve walking performance." ]

[ "19763813" ]

[ "Comparing couples' and individual voluntary counseling and testing for HIV at antenatal clinics in Tanzania: a randomized trial." ]

[ "Voluntary counseling and testing (VCT) for couples (CVCT) is an important HIV-prevention effort in sub-Saharan Africa where a substantial proportion of HIV transmission occurs within stable partnerships. This study aimed to determine the acceptance and effectiveness of CVCT as compared to individual VCT (IVCT). 1,521 women attending three antenatal clinics in Dar es Salaam were randomized to receive IVCT during that visit or CVCT with their husbands at a subsequent visit. The proportion of women receiving test results in the CVCT arm was significantly lower than in the IVCT arm (39 vs. 71%). HIV prevalence overall was 10%. In a subgroup analysis of HIV-positive women, those who received CVCT were more likely to use preventive measures against transmission (90 vs. 60%) and to receive nevirapine for themselves (55 vs. 24%) and their infants (55 vs. 22%) as compared to women randomized to IVCT. Uptake of CVCT is low in the antenatal clinic setting. Community mobilization and couple-friendly clinics are needed to promote CVCT." ]

[ "18056558" ]

[ "Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents." ]

[ "To compare the effects of a single nocturnal dose of buckwheat honey or honey-flavored dextromethorphan (DM) with no treatment on nocturnal cough and sleep difficulty associated with childhood upper respiratory tract infections.\n A survey was administered to parents on 2 consecutive days, first on the day of presentation when no medication had been given the prior evening and then the next day when honey, honey-flavored DM, or no treatment had been given prior to bedtime according to a partially double-blinded randomization scheme.\n A single, outpatient, general pediatric practice.\n One hundred five children aged 2 to 18 years with upper respiratory tract infections, nocturnal symptoms, and illness duration of 7 days or less.\n A single dose of buckwheat honey, honey-flavored DM, or no treatment administered 30 minutes prior to bedtime.\n Cough frequency, cough severity, bothersome nature of cough, and child and parent sleep quality.\n Significant differences in symptom improvement were detected between treatment groups, with honey consistently scoring the best and no treatment scoring the worst. In paired comparisons, honey was significantly superior to no treatment for cough frequency and the combined score, but DM was not better than no treatment for any outcome. Comparison of honey with DM revealed no significant differences.\n In a comparison of honey, DM, and no treatment, parents rated honey most favorably for symptomatic relief of their child's nocturnal cough and sleep difficulty due to upper respiratory tract infection. Honey may be a preferable treatment for the cough and sleep difficulty associated with childhood upper respiratory tract infection.\n clinicaltrials.gov Identifier: NCT00127686." ]

[ "2015715", "9363869", "6322957", "7908358", "2547030" ]

[ "The first international urokinase/warfarin trial in colorectal cancer.", "Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study.", "Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75.", "Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer.", "A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B." ]

[ "Three hundred and forty-four patients with operable colorectal adenocarcinoma, Dukes' stage B or C, were entered into a randomized controlled trial of intraoperative and postoperative intravenous urokinase and/or long-term sodium warfarin therapy. The factorial design of the trial allowed evaluation of each therapy separately. Age, sex, Dukes' stage and cancer site were similar in the treatment groups. Using life-table methods, survival and recurrence/metastases free survival were estimated up to 6 years postoperatively. No significant effects of either therapy on these endpoints were found.", "Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC.\n Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity.\n There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103).\n Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.", "VA Cooperative Study #75 was established to test in a controlled, randomized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy. No differences in survival were observed between warfarin-treated and control groups for advanced non-small cell lung, colorectal, head and neck and prostate cancers. However, warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression (P = 0.016) and a significant improvement in survival (P = 0.018) for patients with small cell carcinoma of the lung, including the subgroup of patients with disseminated disease at the time of randomization (P = 0.013). A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non-small cell lung cancer who had minimal disease at randomization. These results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung. Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present.", "Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1.3 to 1.9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2.6 (SD 1.2) mg for the warfarin group and the mean INR was 1.52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p = 0.45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p = 0.031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.", "The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease." ]

[ "9872200", "10859037", "7651472", "12358327", "12747812", "12536700", "12447511", "8099639" ]

[ "Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure.", "Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial.", "Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.", "Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial.", "[Noninvasive positive pressure ventilation for acute respiratory failure in chronic obstructive pulmonary disease in a general respiratory ward].", "[Effects of noninvasive positive pressure ventilation on gas exchange and patients' transformation in chronic obstructive pulmonary disease and respiratory failure].", "Noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial.", "Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease." ]

[ "To compare the efficacy of standard medical therapy (ST) and noninvasive mechanical ventilation additional to standard medical therapy in hypercapnic acute respiratory failure (HARF).\n Single center, prospective, randomized, controlled study.\n Pulmonary medicine directed critical care unit in a university hospital.\n Between March 1993 and November 1996, 30 HARF patients were randomized to receive ST or noninvasive positive pressure ventilation (NPPV) in addition to ST.\n NPPV was given with an air-cushioned face via a mechanical ventilator (Puritan Bennett 7200) with initial setting of 5 cm H2O continuous positive airway pressure and 15 cm H2O pressure support.\n At the time of randomization, patients in the ST group had (mean+/-SD) PaO2 of 54+/-13 mm Hg, PaCO2 of 67+/-11 mm Hg, pH of 7.28+/-0.02, and respiratory rate of 35.0+/-5.8 breaths/min. Patients in the NPPV group had PaO2 of 55+/-14, PaCO2 of 69+/-15, pH of 7.27+/-0.07, and respiratory rate of 34.0+/-8.1 breaths/min. With ST, there was significant improvement of only respiratory rate (p < 0.05). However, with NPPV, PaO2 (p < 0.001), PaCO2 (p < 0.001), pH (p < 0.001), and respiratory rate (p < 0.001) improved significantly compared with baseline. Six hours after randomization, pH (p < 0.01) and respiratory rate (p < 0.01) in NPPV patients were significantly better than with ST. Hospital stay for NPPV vs ST patients was, respectively, 11.7+/-3.5 and 14.6+/-4.7 days (p < 0.05). One patient in the NPPV group required invasive mechanical ventilation. The conditions of six patients in the ST group deteriorated and they were switched to NPPV; this was successful in four patients, two failures were invasively ventilated.\n This study suggests that early application of NPPV in HARF patients facilitates improvement, decreases need for invasive mechanical ventilation, and decreases the duration of hospitalization.", "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.", "In patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation may be used in an attempt to avoid endotracheal intubation and complications associated with mechanical ventilation.\n We conducted a prospective, randomized study comparing noninvasive pressure-support ventilation delivered through a face mask with standard treatment in patients admitted to five intensive care units over a 15-month period.\n A total of 85 patients were recruited from a larger group of 275 patients with chronic obstructive pulmonary disease admitted to the intensive care units in the same period. A total of 42 were randomly assigned to standard therapy and 43 to noninvasive ventilation. The two groups had similar clinical characteristics on admission to the hospital. The use of noninvasive ventilation significantly reduced the need for endotracheal intubation (which was dictated by objective criteria): 11 of 43 patients (26 percent) in the noninvasive-ventilation group were intubated, as compared with 31 of 42 (74 percent) in the standard-treatment group (P < 0.001). In addition, the frequency of complications was significantly lower in the noninvasive-ventilation group (16 percent vs. 48 percent, P = 0.001), and the mean (+/- SD) hospital stay was significantly shorter for patients receiving noninvasive ventilation (23 +/- 17 days vs. 35 +/- 33 days, P = 0.005). The in-hospital mortality rate was also significantly reduced with noninvasive ventilation (4 of 43 patients, or 9 percent, in the noninvasive-ventilation group died in the hospital, as compared with 12 of 42, or 29 percent, in the standard-treatment group; P = 0.02).\n In selected patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation can reduce the need for endotracheal intubation, the length of the hospital stay, and the in-hospital mortality rate.", "The aim of the present study was to clarify whether the known effects of noninvasive positive-pressure ventilation (NPPV) in patients with respiratory failure are real or due to placebo effects and whether early application of NPPV in the emergency department leads to rapid improvement of the patients condition and outcome. A prospective randomised placebo-controlled study was conducted in 20 patients with severe acute respiratory failure (ARF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute pulmonary oedema, not improving under conventional medical therapy and on the edge of intubation. Patients received either conventional medical therapy plus two-level NPPV (hi-level NPPV) or conventional medical therapy plus \"placebo\" NPPV. The main outcome measures involved the need for endotracheal intubation in the bi-level NPPV arm and in the placebo arm after crossing over to active NPPV. Morbidity, length of stay, mortality and the effect of the ventilatory mode on clinical, arterial-blood gas parameters, and the sternocleidomastoid muscles electromyogram (EMG) activity were also measured. The 10 patients in the active NPPV group rapidly improved and none needed intubation. Placebo NPPV resulted in no change in the clinical condition of patients that continued to worsen and the 10 patients were crossed over to active NPPV. Three patients were intubated. No differences in terms of morbidity, length of stay or mortality between the two groups were observed. Active NPPV (but not placebo NPPV) led to a rapid and significant improvement in the clinical parameters, pH and the carbon dioxide tension in arterial blood and to a decrease in respiratory frequency and sternocleidomastoid EMG activity. Early application of bi-level noninvasive positive-pressure ventilation in patients with severe acute respiratory failure, due to chronic obstructive pulmonary disease and acute pulmonary oedema, leads to a rapid improvement in clinical status and blood gases. Noninvasive positive-pressure ventilation had no placebo effect.", "In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), noninvasive ventilatory support (NPPV) with bilevel positive airway pressure (BiPAP) may improve clinical and physiological parameters. The present study used a randomized, prospective design to evaluate the possible benefits of NPPV plus standard therapy versus standard therapy alone in patients admitted with acute hypercapnic respiratory failure in a respiratory unit of a tertiary hospital.\n Forty-one patients were included in the study. Of them, 20 were randomly allocated to receive NPPV with a standard mask connected to a BiPAP ventilatory assist device (Respironics Inc, Murrysville, PA) and 21 to standard therapy. Both groups had similar characteristics upon their admission in the hospital.\n The use of noninvasive ventilation significantly reduced the respiratory rates and improved the conscious level within the first 2 h (p < 0.001). There were significant differences in PaCO2 and pH (p < 0.05) at 6 h of treatment. The need for intubation was 5% in the NPPV group vs 14% in the control group. The length of hospital stay was significantly shorter in the NPPV group (7 vs 10 days; p < 0.01). Nasal NPPV was well tolerated and complications were uncommon and mild.\n Early use of noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease leads to a more rapid improvement of physiological variables. Moreover, it is possible to apply this treatment in a general respiratory ward.", "This paper was to observe the effects of noninvasive positive pressure ventilation (NPPV) on gas exchange and patients' transformation and to evaluate their clinical value.\n Patients were randomly treated by either NPPV, or conventional medicine. The arterial blood gas readings, heart rates (HR), and respiratory rates (HR) were obtained at admission after the treatment. It was necessary to intubate when the clinical deterioation was marked by PaCO2 > 70 mmHg, PaCO2 gradually increasing 5-10 mmHg, pH decreasing 0.05-0.1 or mental obstacle, or PaO2 < 45 mmHg.\n NPPV significantly decreased the PaCO2 level, HR, and RR, significantly increased the PaO2 level, and also decreased the opportunity of intubation.\n The results suggest that NPPV can improve the gas exchange and reduce the need of intubation in COPD patients with acute respiratory failure.", "We conducted a randomized prospective study comparing noninvasive positive pressure ventilation (NPPV) with conventional mechanical ventilation via endotracheal intubation (ETI) in a group of patients with chronic obstructive pulmonary disease who failed standard medical treatment in the emergency ward after initial improvement and met predetermined criteria for ventilatory support.\n Prospective randomized study in a university hospital 13-bed general ICU.\n Forty-nine patients were randomly assigned to receive NPPV (n=23) or conventional ventilation (n=26).\n both NPPV and conventional ventilation significantly improved gas exchanges. The two groups had similar length of ICU stay, number of days on mechanical ventilation, overall complications, ICU mortality, and hospital mortality. In the NPPV group 11 (48%) patients avoided intubation, survived, and had a shorter duration of ICU stay than intubated patients. One year following hospital discharge the NPPV group had fewer patients readmitted to the hospital (65% vs. 100%) or requiring de novo permanent oxygen supplementation (0% vs. 36%).\n The use of NPPV in patients with chronic obstructive pulmonary disease and acute respiratory failure requiring ventilatory support after failure of medical treatment avoided ETI in 48% of the patients, had the same ICU mortality as conventional treatment and, at 1-year follow-up was associated with fewer patients readmitted to the hospital or requiring for long-term oxygen supplementation. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1503-3).", "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." ]

[ "14530224", "11439734", "11252687", "11115219", "12398962", "17039120", "14613272", "11754710", "14506910", "11304662", "11405384", "10817549", "10555907", "10500058", "12051399", "14624289", "15086644" ]

[ "Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial.", "Effect of rofecoxib therapy on measures of health-related quality of life in patients with osteoarthritis.", "Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis.", "Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Osteoarthritis Studies Group.", "Effects of celecoxib and rofecoxib on blood pressure and edema in patients > or =65 years of age with systemic hypertension and osteoarthritis.", "COX-2 specific inhibitors in the management of osteoarthritis of the knee: a placebo-controlled, randomized, double-blind study.", "Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis: appropriate trial design considerations and results of a randomized, placebo-controlled trial.", "Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial.", "A randomised, double-blind, clinical trial comparing the efficacy of nimesulide, celecoxib and rofecoxib in osteoarthritis of the knee.", "Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients.", "A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis.", "Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac sodium: results of a one-year, randomized, clinical trial in patients with osteoarthritis of the knee and hip. Rofecoxib Phase III Protocol 035 Study Group.", "Effect of specific COX-2 inhibition in osteoarthritis of the knee: a 6 week double blind, placebo controlled pilot study of rofecoxib. Rofecoxib Osteoarthritis Pilot Study Group.", "A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group.", "Renal tolerability of three commonly employed non-steroidal anti-inflammatory drugs in elderly patients with osteoarthritis.", "Comparative evaluation of the effectiveness and tolerability of nimesulide versus rofecoxib taken once a day in the treatment of patients with knee osteoarthritis.", "Efficacy and safety of rofecoxib 12.5 mg versus nabumetone 1,000 mg in patients with osteoarthritis of the knee: a randomized controlled trial." ]

[ "Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform.\n To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis.\n Randomized, controlled trial.\n 600 office and clinical research sites.\n 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine.\n Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted.\n Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12.\n Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events.\n In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.", "Bodily pain and physical disability can negatively impact health-related quality of life (HRQL) in patients with osteoarthritis (OA).\n To assess the effects of treatment with a new agent, rofecoxib, on HRQL in patients with OA.\n Randomized, double-blind, 6-week clinical trial comparing treatment with rofecoxib, 5 to 50 mg, with placebo in 672 patients with OA of the hip or knee.\n Patient HRQL was assessed at baseline and at the end of treatment using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).\n At 6 weeks, mean change from baseline in all SF-36 mental and physical health domain scores demonstrated significant improvement with rofecoxib use (P < .05 for all doses for all SF-36 domains), with evidence of a dose-response relation. Improvements in mental and physical HRQL domains with rofecoxib treatment were significantly greater than those with placebo treatment (P < .05 for each dose of rofecoxib vs placebo for all domains except general health) and highly correlated with improvements observed using disease-specific OA outcome measures such as the Western Ontario and McMaster Universities Osteoarthritis Index-visual Analog 3.0 OA index pain and physical function subscales. The effect of rofecoxib vs placebo treatment on mental health largely disappeared after adjustment for improvement in OA disease-specific measures.\n Rofecoxib treatment increased physical and mental HRQL domain scores on the SF-36. Improvements in mental health with rofecoxib use primarily resulted from effective treatment of OA (i.e., reduction in pain and improvement in physical function).", "To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).\n Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting).\n Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy.\n Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).", "Rofecoxib, a cyclooxygenase 2 inhibitor (sometimes known as a specific cyclooxygenase 2 inhibitor or Coxib), is used in osteoarthritis (OA). Published information indicates rofecoxib's improved gastrointestinal safety profile over nonselective nonsteroidal anti-inflammatory agents (NSAIDs).\n To evaluate the efficacy and safety of rofecoxib in treating OA in 2 studies.\n Two randomized, double-blind, parallel-group studies in patients with OA of the knee or hip were conducted using identical entry criteria and end points. A 6-week placebo-controlled trial in 736 patients compared 12.5 and 25 mg of rofecoxib once daily with 800 mg of ibuprofen 3 times daily, and a 1-year study compared 12.5 and 25 mg of rofecoxib once daily with 50 mg of diclofenac 3 times daily in 693 patients.\n Rofecoxib, at 12.5 and 25 mg, demonstrated efficacy clinically comparable with ibuprofen, assessed by 3 primary end points according to predefined comparability criteria. Both rofecoxib doses and ibuprofen provided significantly greater efficacy than placebo on all primary end points at 6 weeks. Both rofecoxib doses and diclofenac showed similar efficacy over 1 year. All treatments were well tolerated.\n Rofecoxib is effective in treating OA with once-daily dosing for 6 weeks and 1 year. Rofecoxib was generally safe and well-tolerated in OA patients for 6 weeks and 1 year. Arch Fam Med. 2000;9:1124-1134", "Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), including the cyclooxygenase-2 (COX-2) specific inhibitors, with antihypertensive medication is common practice for many patients with arthritis. This study evaluated the effects of celecoxib 200 mg/day and rofecoxib 25 mg/day on blood pressure (BP) and edema in a 6-week, randomized, parallel-group, double-blind study in patients > or =65 years of age with osteoarthritis who were treated with fixed antihypertensive regimens. One thousand ninety-two patients received study medication (celecoxib, n = 549; rofecoxib, n = 543). Significantly more patients in the rofecoxib group compared with the celecoxib group developed increased systolic BP (change >20 mm Hg plus absolute value > or =140 mm Hg) at any time point (14.9% vs 6.9%, p <0.01). Rofecoxib caused the greatest increase in systolic BP in patients receiving angiotensin-converting enzyme inhibitors or beta blockers, whereas those on calcium channel antagonists or diuretic monotherapy receiving either celecoxib or rofecoxib showed no significant increases in BP. Clinically significant new-onset or worsening edema associated with weight gain developed in a greater percentage of patients in the rofecoxib group (7.7%) compared with the celecoxib group (4.7%) (p <0.05). Thus, in patients with controlled hypertension on a fixed antihypertensive regimen, careful monitoring of BP is warranted after the initiation of celecoxib or rofecoxib therapy.", "COX-2 specific inhibitors have demonstrated significant safety advantages and comparable efficacy in osteoarthritis (OA) compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs), but no direct comparative trials between COX-2 specific inhibitors have been published. In this double-blind, placebo-controlled, parallel group, multicenter study, 182 patients (> or =40 years old) with OA of the knee were randomly assigned to treatment with celecoxib 200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n = 59), or placebo (n = 60) for 6 weeks. Arthritis assessments were performed at baseline and Weeks 3 and 6, or at early termination. At Week 6, celecoxib and rofecoxib treatment resulted in similar mean changes from baseline (p > 0.55) in arthritis pain visual analogue scale, patient's global assessment, and total score for WOMAC; all changes were superior to placebo (p < 0.05). In the patient's global assessment of arthritis pain at Week 6, 79% of celecoxib-treated and 78% of rofecoxib-treated patients improved by > or =1 grade, compared with 50% of placebo patients (celecoxib, p = 0.025; rofecoxib, p = 0.020). Adverse event incidences were similar among the active comparators; however, celecoxib-treated patients had significantly fewer adverse gastrointestinal symptoms compared with rofecoxib-treated patients, which suggests that celecoxib may have a better gastrointestinal tolerability profile than rofecoxib at these doses. Adverse events that prompted withdrawal occurred in fewer than 7% of patients, and the overall incidences were similar between the active agents. Once-daily doses of celecoxib 200 mg and rofecoxib 25 mg offer comparable efficacy and are an effective alternative to conventional NSAIDs in the management of OA.", "To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA).\n In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination).\n In primary measures of efficacy (OA pain score on a 100-mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was -2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events.\n Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.", "Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or specific inhibitors of cyclooxygenase 2 (COX-2).\n To assess the relative therapeutic efficacy of rofecoxib, celecoxib, and acetaminophen in adults with OA.\n Randomized, parallel-group, double-blind trial, conducted from June 1999 to February 2000, in 29 clinical centers in the United States.\n Three hundred eighty-two patients aged at least 40 years who had OA of the knee that was previously treated with NSAIDs or acetaminophen.\n Patients were randomly assigned to receive rofecoxib, 12.5 mg/d (n = 96); rofecoxib, 25 mg/d (n = 95); celecoxib, 200 mg/d (n = 97); or acetaminophen, 4000 mg/d (n = 94) for 6 weeks.\n Assessments over days 1 to 6 and over 6 weeks included pain on walking, night pain, pain at rest, and morning stiffness as measured on a Western Ontario McMaster Universities Osteoarthritis Index (100-mm visual analog scale [VAS]) and global response to therapy compared among 4 treatment groups.\n 79% of patients completed the study. More patients treated with acetaminophen discontinued early due to lack of efficacy than patients treated with COX-2 inhibitors (31% vs 18%-19%). Efficacy assessed in the first 6 days of therapy showed greatest response to rofecoxib, 25 mg/d, followed by rofecoxib, 12.5 mg/d, celecoxib, and acetaminophen, respectively, in terms of relief of pain on walking (-32.2, - 29.0, - 26.4, and -20.6 mm change on the VAS; P</=.04 for all others vs acetaminophen; P =.05 for 25-mg rofecoxib vs celecoxib), rest pain (-21.8, - 18.6, - 15.5, and - 12.5 mm; P</=.02 for either dose of rofecoxib vs acetaminophen and P =.02 for rofecoxib, 25 mg/d, vs celecoxib), night pain (-25.2, - 22.0, - 18.7, and - 18.8 mm; P =.04 for rofecoxib, 25 mg/d, vs both acetaminophen and celecoxib), and morning stiffness (-30.4, - 28.4, - 25.7, and - 20.9 mm; P</=.02 for either dose of rofecoxib vs acetaminophen). Over 6 weeks, rofecoxib, 25 mg/d, provided greatest response for night pain (P<.002 vs celecoxib and P =.006 vs acetaminophen and P =.02 vs rofecoxib, 12.5 mg/d), composite pain subscale (P</=.03 vs all other treatments), stiffness subscale (P</=.04 vs celecoxib and acetaminophen), and physical function subscale (P =.001 vs acetaminophen). Global responses over 6 weeks showed a similar pattern (good or excellent response at week 6: 60%, 56%, 46%, and 39%, respectively; P</=.03 for rofecoxib, 25 mg/d, vs celecoxib and acetaminophen; P =.02 for rofecoxib, 12.5 mg/d, vs acetaminophen). All treatments were generally safe and well tolerated.\n Rofecoxib, 25 mg/d, provided efficacy advantages over acetaminophen, 4000 mg/d, celecoxib, 200 mg/d, and rofecoxib, 12.5 mg, for symptomatic knee OA.", "Joint pain is the main complaint in patients affected by osteoarthritis (OA), and NSAIDs are commonly used to treat pain associated with OA. Over the past few years, cyclo-oxygenase (COX)-2-selective inhibitors have been proved to have certain advantages over non-selective NSAIDs and have been increasingly used for pain management in patients with OA.\n The main objective of this randomised, double-blind, within-patient study was to compare the analgesic efficacy of three COX-2 inhibitors in 30 patients affected by symptomatic OA of the knee. We evaluated the effects of oral nimesulide (100mg), celecoxib (200mg) and rofecoxib (25mg). Each drug was administered for 7 days.\n Analgesic efficacy was determined using the patient's assessment of pain on a visual analogue scale (VAS) and by total pain relief over 3 hours (TOPAR3) on the first and last days of treatment. In addition, the overall analgesic efficacy and tolerability were determined by a global assessment by the patient at the end of each week of treatment, using 5-point categorical scales. At the end of the study, each patient was asked about which of the three forms of treatment they would choose as a continuation of the pain therapy.\n Taking all the results into consideration, nimesulide proved to be significantly more effective in providing symptomatic relief than did celecoxib and rofecoxib. Furthermore, nimesulide provided more rapid relief of pain associated with walking than did the other two drugs tested. Patients expressed similar preference for nimesulide and rofecoxib, but a lesser preference for celecoxib treatment. No patient withdrew from the study because of adverse events and the three different forms of treatment were generally safe and well tolerated.\n The present data confirm our previous observations in patients with rheumatoid arthritis, further suggesting that nimesulide represents an effective agent for the treatment of joint pain, with particular reference to the rapid onset of its analgesic effect.", "Arthritis and hypertension are common comorbid conditions affecting elderly adults. Use of nonsteroidal anti-inflammatory drugs in patients treated with antihypertensive medication can lead to destabilization of blood pressure control and other cardiorenal events. The potential for similar interactions with cyclooxygenase-2-specific inhibitors has not been fully explored. The authors evaluated the cardiorenal safety of two new cyclooxygenase-2-specific inhibitors, celecoxib and rofecoxib.\n This study was a 6-week, randomized, parallel-group, double-blind trial in patients with osteoarthritis who were > or =65 years of age and were taking antihypertensive agents. Patients received once-daily celecoxib 200 mg or rofecoxib 25 mg. The primary endpoints were the development of edema, changes in systolic blood pressure, and changes in diastolic blood pressure as measured at any time point in the study. Measurements occurred at baseline and after 1, 2, and 6 weeks of treatment.\n Eight hundred ten patients received study medication (celecoxib, n = 411; rofecoxib, n = 399). Nearly twice as many rofecoxib- compared with celecoxib-treated patients experienced edema (9.5% vs. 4.9%, P = 0.014). Systolic blood pressure increased significantly in 17% of rofecoxib- compared with 11% of celecoxib-treated patients (P = 0.032) at any study time point. Diastolic blood pressure increased in 2.3% of rofecoxib- compared with 1.5% of celecoxib-treated patients (P = 0.44). At week 6, the change from baseline in mean systolic blood pressure was +2.6 mmHg for rofecoxib compared with -0.5 mmHg for celecoxib (P = 0.007).\n Patients taking antihypertensive therapy and receiving cyclooxygenase-2-specific inhibitors should be monitored for the development of cardiorenal events. Patients receiving celecoxib experienced less edema and less destabilization of blood pressure control compared with those receiving rofecoxib.", "This 6-week study was conducted to test the efficacy, safety, and tolerability of rofecoxib (a selective COX-2 inhibitor) compared to nabumetone (a non-selective NSAID) and placebo in osteoarthritis (OA) patients aged 80 and older. Three hundred forty-one patients, mean age 83 years, were randomized. Allocations were made in an approximately 1:2:1:2 ratio (placebo: 12.5 mg rofecoxib: 25 mg rofecoxib: 1500 mg nabumetone). Least square mean changes from baseline in the primary efficacy endpoint, Patient Global Assessment of Disease Status, were as follows (with negative numbers indicating improvement): -14.85 mm for placebo; -25.34 mm for 12.5 mg rofecoxib; -25.40 mm for 25 mg of rofecoxib; and -25.95 mm for nabumetone (p<0.001 for all active treatments vs placebo.) Results from secondary endpoints, including the 3 WOMAC sub-scales (pain, stiffness, and disability) and the Investigator Global Assessment of Disease Status, were consistent with those for the primary endpoint. No significant between-group differences were observed in the proportions of patients who discontinued treatment due to either clinical or laboratory adverse experiences. Renal safety (edema and hypertension adverse experiences) was similar for rofecoxib and nabumetone. No gastroduodenal ulcers occurred; however, the demonstration of gastrointestinal risk with rofecoxib or nabumetone was beyond the scope of this trial. We conclude that in patients 80 years and older, rofecoxib, 12.5 mg and 25 mg once daily, demonstrated clinical efficacy for the treatment for OA as did 1500 mg of nabumetone. Rofecoxib and nabumetone were generally well tolerated in this elderly population.", "To compare the clinical efficacy of rofecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2), with that of diclofenac in patients with osteoarthritis (OA) and to evaluate the safety and tolerability of rofecoxib.\n We performed a randomized, double-blind, active comparator-controlled trial in 784 adults with OA of the knee or hip. Patients were randomized to 1 of 3 treatment groups: 12.5 mg of rofecoxib once daily, 25 mg of rofecoxib once daily, and 50 mg of diclofenac 3 times daily. Clinical efficacy and safety were evaluated over a 1-year continuous treatment period.\n Rofecoxib at dosages of 12.5 and 25 mg demonstrated efficacy that was clinically comparable to that of diclofenac, as assessed by all 3 primary end points according to predefined comparability criteria. Results from secondary end points were consistent with those of the primary end points. There were small statistical differences favoring diclofenac for 2 of the end points. All treatments were well tolerated.\n Rofecoxib was well tolerated and provided efficacy that was clinically comparable, according to predefined statistical criteria, to that of 150 mg of diclofenac per day in this 1-year study. Specific inhibition of COX-2 provided therapeutic efficacy in OA.", "To determine the efficacy and safety of the cyclooxygenase 2 (COX-2) specific inhibitor, rofecoxib in patients with osteoarthritis (OA) of the knee.\n Rofecoxib, 25 mg or 125 mg once daily, was compared with placebo in a 6 week, double blind, parallel group, randomized, multicenter study of 219 patients with knee OA.\n Both doses of rofecoxib produced clinically significant improvement as assessed by primary (e.g., WOMAC Pain Subscale 0-100 mm, decrease from baseline: placebo: 7.1 mm; rofecoxib 25 mg: 28.1 mm, rofecoxib 125 mg: 28.0 mm; p < 0.001 rofecoxib vs placebo) and secondary efficacy (p < 0.05) criteria compared with placebo. Clinical improvement with the 25 mg dose was similar to that with the 125 mg dose. Both rofecoxib doses were generally well tolerated.\n Specific inhibition of COX-2 by 25 and 125 mg rofecoxib, administered once daily, resulted in clinically meaningful improvements in patients with OA. This study confirms that COX-2 derived prostanoids are important clinical mediators of pain and other symptoms of knee OA and that inhibition of COX-1 is not required to provide clinical benefit.", "Prostaglandin production in the normal gastrointestinal tract, believed to be critical for mucosal integrity, is mediated by cyclooxygenase (COX)-1, whereas prostaglandin production at inflammatory sites seems to occur via induction of COX-2. We hypothesized that COX-2-specific inhibition with rofecoxib (25 mg once daily) in the treatment of patients with osteoarthritis would cause fewer gastroduodenal ulcers than an equally effective dose of ibuprofen (800 mg 3 times a day), a nonspecific COX inhibitor.\n A total of 742 osteoarthritis patients without ulcers on baseline endoscopy were randomly assigned to receive rofecoxib (25 or 50 mg once daily), ibuprofen (800 mg 3 times daily), or placebo. Endoscopy was repeated at 6, 12, and 24 weeks. At 16 weeks, by study design, 95% of the placebo group and 5% of the other groups were discontinued.\n The cumulative incidence of gastroduodenal ulcers >/=3 mm with rofecoxib (25 or 50 mg once daily) was significantly (P < 0.001) lower than with ibuprofen and was statistically equivalent to placebo at week 12 (placebo, 9.9%; 25 mg rofecoxib, 4.1%; 50 mg rofecoxib, 7.3%; and ibuprofen, 27.7%). At 24 weeks, ulcer rates were 25 mg rofecoxib, 9. 6%; 50 mg rofecoxib, 14.7%; and ibuprofen, 45.8% (P < 0.001, ibuprofen vs. 25 and 50 mg rofecoxib).\n Rofecoxib, at doses 2-4 times the dose demonstrated to relieve symptoms of osteoarthritis, caused significantly less gastroduodenal ulceration than ibuprofen, with ulcer rates comparable to placebo.", "The primary endpoint of this study was to compare the renal tolerability of amtolmetin guacyl (AMG), diclofenac and rofecoxib in elderly patients with symptomatic osteoarthritis (OA). The assessment of efficacy was the secondary endpoint.\n 90 patients who satisfied the American College of Rheumatology classification criteria for hand, hip or knee OA were randomly assigned to 3 treatment groups receiving either: AMG 1,200 mg over thefirst 3 days and and 600 mg/day thereafter; diclofenac 150 mg/day; or rofecoxib 25 mg/day for 2 weeks. At baseline and after therapy patients were clinically assessed by the same examiner who was unaware of the treatment arm assignement. Serum and urinary parameters of renal function and the outcome measures of efficacy were evaluated before (t(0)) and after therapy (t(1)).\n Diclofenac produced a significant reduction in creatinine clearance (t(0) = 88.93 +/- 11.59; t(1) = 75.90 +/- 16.32; p: < 0.001) and in the daily urine volume (t(0) = 1,337.93 +/- 202.07; t(1) = 1,027.59 +/- 249.14; p: < 0.001). In the same treatment group a significant increase in serum creatinine, blood urea nitrogen, uric acid and potassium were observed. Rofecoxib treated patients showed a significant increase in body weight (t(0) = 75.31 +/- 4.26; t(1) = 76.54 +/- 4.84; p: < 0.001), systolic blood pressure (t(0) = 144 +/- 10.86; t(1) = 154 +/- 11.8; p < 0.001), diastolic blood pressure (t(0) = 80 +/- 6.05; t(1) = 89 +/- 7.66; p < 0.001) and serum sodium (t(0) = 138.73 +/- 1.28; t(1) = 140.12 +/- 1.80; p < 0.005) associated with a significant decrease in the daily urine volume (t(0) = 1294.64 +/- 205.21; t, = 1,115.48 +/- 238.47; p < 0.001) and creatinine clearance (t(0)= 86.73 +/- 8.14; t(1) = 83.15 +/- 7.96; p < 0.01). No significant changes in the clinical and humoral parameters were recorded in AMG treated patients. Diclofenac was more efficacious than the other 2 drugs (p < 0.001). No differences were observed between AMG and rofecoxib. Side effects related to altered kidney function were significantly higher in the rofecoxib group (p < 0.005).\n Diclofenac mainly impaired blood renal flow and the glomerularfiltration rate, while rofecoxib negatively influenced the renal sodium-water exchange. AMG demonstrated a renal sparing effect, although the eract mechanism is unclear", "The treatment of osteoarthritis, a common degenerative joint disease, is focused on the relief of symptoms, mainly pain, and sometimes joint stiffness. Nonsteroidal antiinflammatory drugs are considered the treatment of choice in cases where the pain cannot be reduced with acetaminophen. This trial was conducted to compare the effectiveness of 2 nonsteroidal antiinflammatory drugs taken once daily to relieve the symptoms of osteoarthritis.\n To compare the safety and efficacy of 2 nonsteroidal antiinflammatory drugs, nimesulide versus rofecoxib, given once a day in patients with knee osteoarthritis.\n 114 patients with the diagnosis of knee osteoarthritis were recruited in a randomized, double-blinded fashion, and they received a daily dose of either 300 mg of nimesulide retard or 25 mg of rofecoxib. The effectiveness was evaluated by means of: visual analog scale 0 to 10 cm measured at 0, 15, 30, and 45 minutes after the first dose and then after 2, 3, 15, and 30 days of continuous drug dosing. The quality of life was assessed by the scale of the Western Ontario and McMaster Universities on days 0, 15, and 30. The patients' opinions and that of the physicians were recorded at the end of the study.\n The 2 groups of patients were matched for race, sex, menopause status (for females), pathologic antecedents, the duration of osteoarthritis, and the history of nonsteroidal antiinflammatory drug therapy; however, patients' affected knees could differ in the 2 treatments. The 2 drugs were equally effective in terms of overall improvement of pain and the quality of life; they were equally well tolerated. However, significant differences were found between the 2 drugs in favor of nimesulide in the relief of the pain on days 2, 3, and 30, and in the scale of Western Ontario and McMaster Universities Osteoarthritis index on day 15 and 30.\n In this trial, both medications were effective in improving the pain and the quality of life in patients with knee osteoarthritis; however, nimesulide, compared with rofecoxib, was quicker in reducing the pain and was more effective on days 2, 3, and 30. Nimesulide was also superior in improving the quality of life after 30 days of treatment.", "To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis (OA) of the knee.\n A 6-week, randomized, parallel-group, double-blind, placebo-controlled study.\n One hundred thirteen outpatient sites in the United States.\n A total of 1,042 male and female patients aged 40 and older with OA of the knee (>6 months).\n Rofecoxib 12.5 mg once a day (n=424), nabumetone 1,000 mg once a day (n=410), or placebo (n=208) for 6 weeks.\n The primary efficacy endpoint was patient global assessment of response to therapy (PGART) over 6 weeks, which was also specifically evaluated over the first 6 days. The main safety measure was adverse events during the 6 weeks of treatment.\n The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib (55.4%) than nabumetone (47.5%; P=.018) or placebo (26.7%; P<.001 vs rofecoxib or nabumetone). Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib (2 days) than with nabumetone (4 days, P=.002) and placebo (>5 days, P<.001) (nabumetone vs placebo; P=.007). The safety profiles of rofecoxib and nabumetone were generally similar, including gastrointestinal, hypertensive, and renal adverse events.\n Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily. Both therapies were generally well tolerated." ]

[ "18624803", "11128820", "10437184", "11531895", "1594255", "16055451", "2262314", "17059439", "17955168" ]

[ "Acupuncture in patients with headache.", "Acupuncture for episodic tension-type headache: a multicentre randomized controlled trial.", "Does psychological testing help to predict the response to acupuncture or massage/relaxation therapy in patients presenting to a general neurology clinic with headache?", "Needle acupuncture in tension-type headache: a randomized, placebo-controlled study.", "Traditional Chinese acupuncture in tension-type headache: a controlled study.", "Acupuncture in patients with tension-type headache: randomised controlled trial.", "Health status in patients with tension headache treated with acupuncture or physiotherapy.", "Chronic tension-type headache treated with acupuncture, physical training and relaxation training. Between-group differences.", "Acupuncture for tension-type headache: a multicentre, sham-controlled, patient-and observer-blinded, randomised trial." ]

[ "We aimed to investigate the effectiveness of acupuncture in addition to routine care in patients with primary headache (> 12 months, two or more headaches/month) compared with treatment with routine care alone and whether the effects of acupuncture differ in randomized and non-randomized patients. In a randomized controlled trial plus non-randomized cohort, patients with headache were allocated to receive up to 15 acupuncture sessions over 3 months or to a control group receiving no acupuncture during the first 3 months. Patients who did not consent to randomization received acupuncture treatment immediately. All subjects were allowed usual medical care in addition to study treatment. Number of days with headache, intensity of pain and health-related quality of life (SF-36) were assessed at baseline, and after 3 and 6 months using standardized questionnaires. Of 15,056 headache patients (mean age 44.1 +/- 12.8 years, 77% female), 1613 were randomized to acupuncture and 1569 to control, and 11,874 included in the non-randomized acupuncture group. At 3 months, the number of days with headache decreased from 8.4 +/- 7.2 (estimated mean +/-s.e.) to 4.7 +/- 5.6 in the acupuncture group and from 8.1 +/- 6.8 to 7.5 +/- 6.3 in the control group (P < 0.001). Similarly, intensity of pain and quality of life improvements were more pronounced in the acupuncture vs. control group (P < 0.001). Treatment success was maintained through 6 months. The outcome changes in non-randomized patients were similar to those in randomized patients. Acupuncture plus routine care in patients with headache was associated with marked clinical improvements compared with routine care alone.", "A multicentre, randomized clinical trial was undertaken to test the hypothesis that acupuncture is more efficacious than sham control procedure in the prevention of episodic tension-type headache. Fifty subjects were randomized to receive a course of treatment with either brief acupuncture or a sham procedure. Subjects were followed up for 3 months. Changes in headache were assessed by daily diary, the primary outcome measure being the number of days with headache. No significant differences were found between the changes in the two groups for any measure at any time point. Results also show that patient blinding was successful. In conclusion, this study does not provide evidence that this form of acupuncture is effective in the prevention of episodic tension-type headache.", "Patients with chronic headache were offered treatment by acupuncture or massage with relaxation instead of a change in their prescribed medication. They were randomly allocated to either treatment. There was a significant improvement in pain ratings with both treatment types. Specifically a greater effect was seen in migraine patients treated by massage with relaxation when compared to acupuncture. No psychological factors were found to predict response to either treatment. At the end of the study, 13% of patients were significantly more worried that there may be a more serious cause underlying their headache despite reassurance and an improvement in their headache scores.", "A study with needle acupuncture was performed in tension-type headache employing a new placebo acupuncture\n Sixty-nine patients (mean age 48.1 years, SD = 14.1) fulfilling the International Headache Society criteria for tension-type headache were randomly assigned to verum or placebo condition. No significant differences between placebo and verum with respect to visual analogue scale and frequency of headache attacks could be observed immediately, 6 weeks and 5 months after the end of treatment. There was a significant but weak improvement in quality of life parameters (clinical global impressions, Nottingham Health Profile) after verum treatment. In decision tree analyses, the changes in clinical global impressions and headache frequency depended significantly on primary headache frequency with a limit value of 24.5 days headache per month. High values in the von Zerssen Depression Score resulted in high mean visual analogue scale values.", "Thirty patients with tension-type headache were randomly chosen to undergo a trial of traditional Chinese acupuncture and sham acupuncture. Five measures were used to assess symptom severity and treatment response: intensity, duration and frequency of headache pain episodes, headache index and analgesic intake. The five measures were assessed during a 4 week baseline period, after 4 and 8 weeks of treatment, and 1, 6 and 12 months thereafter. Before the start of the study, each patient was administered the MMPI. Split-plot ANOVAs showed that, compared to baseline, at 1 month after the end of treatment and for the 12 month follow-up, the frequency of headache episodes, analgesic consumption and the headache index (but not the duration or intensity of headache episodes) significantly decreased over time; however, no difference between acupuncture and placebo treatment was found. No single MMPI scale predicted the response to treatment, but the mean MMPI profile of acupuncture non-responders showed the presence of 'Conversion V'.", "To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache.\n Three armed randomised controlled multicentre trial.\n 28 outpatient centres in Germany.\n 270 patients (74% women, mean age 43 (SD 13) years) with episodic or chronic tension-type headache.\n Acupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or waiting list control. Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks.\n Difference in numbers of days with headache between the four weeks before randomisation and weeks 9-12 after randomisation, as recorded by participants in headache diaries.\n The number of days with headache decreased by 7.2 (SD 6.5) days in the acupuncture group compared with 6.6 (SD 6.0) days in the minimal acupuncture group and 1.5 (SD 3.7) days in the waiting list group (difference: acupuncture v minimal acupuncture, 0.6 days, 95% confidence interval -1.5 to 2.6 days, P = 0.58; acupuncture v waiting list, 5.7 days, 3.9 to 7.5 days, P < 0.001). The proportion of responders (at least 50% reduction in days with headache) was 46% in the acupuncture group, 35% in the minimal acupuncture group, and 4% in the waiting list group.\n The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache.\n ISRCTN9737659.", "Sixty-two female patients with chronic tension headache were randomly divided into two treatment groups--acupuncture and physiotherapy. Their overall function (Sickness Impact Profile), and mental well-being (Mood Adjective Check List) and the intensity and frequency of headache were assessed before and after treatment. Before treatment the patients showed significantly more dysfunction and less positive mental well-being than a general population sample. Both treatment groups improved in overall function, the physiotherapy group somewhat more. The mental well-being increased only in the physiotherapy group. The intensity and frequency of headache was significantly reduced in both the physiotherapy group and the acupuncture group. The intensity of headache was significantly more improved in the physiotherapy group. The improvement of headache intensity persisted unchanged 7-12 months after treatment.", "The aim of this study was to compare acupuncture, relaxation training and physical training in the treatment of chronic tension-type headache (CTTH). The study comprised 90 consecutive patients with CTTH who were randomly allocated to acupuncture, relaxation training or physical training. Headache intensity, headache-free days and headache-free periods were registered using a visual analogue scale and a headache diary. The measurements were made 4 weeks before, immediately after, and 3 and 6 months after the treatment period. Immediately after the last treatment, the number of headache-free periods and of headache-free days was higher in the relaxation group compared with the acupuncture group. There were no other significant differences between the groups at any time point. The clinical implications of our findings are that relaxation training induced the most pronounced effects directly after the treatment period, compared with acupuncture and physical training.", "Acupuncture treatment is frequently sought for tension-type headache (TTH), but there is conflicting evidence as to its effectiveness. This randomised, controlled, multicentre, patient-and observer-blinded trial was carried out in 122 outpatient practices in Germany on 409 patients with TTH, defined as > or =10 headache days per month of which < or =1 included migraine symptoms. Interventions were verum acupuncture according to the practice of traditional Chinese medicine or sham acupuncture consisting of superficial needling at nonacupuncture points. Acupuncture was administered by physicians with specialist acupuncture training. Ten 30-min sessions were given over a six-week period, with additional sessions available for partial response. Response was defined as >50% reduction in headache days/month at six months and no use of excluded concomitant medication or other therapies. In the intent-to-treat analysis (all 409 patients), 33% of verum patients and 27% of sham controls (p=0.18) were classed as responders. Verum was superior to sham for most secondary endpoints, including headache days (1.8 fewer; 95% CI 0.6, 3.0; p=0.004) and the International Headache Society response criterion (66% vs. 55% response, risk difference 12%, 95% CI: 2%-21%; p=0.024).). The relative risk on the primary and secondary response criterion was very similar ( approximately 0.8); the difference in statistical significance may be due to differences in event rate. TTH improves after acupuncture treatment. However, the degree to which treatment benefits depend on psychological compared to physiological effects and the degree to which any physiological effects depend on needle placement and insertion depth are unclear." ]

[ "9475639", "10979879", "1548998", "16772251", "8100607", "11371683", "10190777", "18320351", "2223891", "11936063", "10416558", "15090799", "16540826" ]

[ "The effect of exercise training on aerobic fitness, immune indices, and quality of life in HIV+ patients.", "Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial.", "Effects of exercise training on men seropositive for the human immunodeficiency virus-1.", "Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial.", "Supervised exercise training improves cardiopulmonary fitness in HIV-infected persons.", "Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults.", "Moderate and high intensity exercise training in HIV-1 seropositive individuals: a randomized trial.", "The effects of exercise training on quality of life in HAART-treated HIV-positive Rwandan subjects with body fat redistribution.", "Exercise intervention attenuates emotional distress and natural killer cell decrements following notification of positive serologic status for HIV-1.", "Effectiveness of a home-based exercise intervention for HIV-infected adults: a randomized trial.", "Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.", "Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients.", "Exercise training in HIV-1-infected individuals with dyslipidemia and lipodystrophy." ]

[ "Thirty four HIV+ patients participated in a 6-wk aerobic exercise training program to determine whether exercise improved aerobic fitness, immune indices, and quality of life.\n Subjects were assigned to three groups: control (no regular aerobic exercise), moderate exercise, and heavy exercise training. At study entry and exit (in each subject) we evaluated aerobic function with a symptom limited cardiopulmonary exercise test, immune indices with CD4 counts and Candida skin tests, viral replication with plasma HIV RNA measurements, and quality of life with a HIV+ population validated questionnaire.\n Aerobic fitness increased significantly in both exercise groups relative to the control group; immune indices changed very little among all three groups; however, the Candida skin tests (mm2) increased significantly in the moderate group; viral replication was essentially unchanged in all three groups; quality of life (QOL) markers improved in both exercising groups but not the control group. There were no opportunistic infections during the study.\n Exercise training resulted in a substantial improvement in aerobic function while immune indices were essentially unchanged. Quality of life markers improved significantly with exercise. Exercise training is safe and effective in this patient group and should be promoted for HIV+ patients.", "Substantial loss of muscle mass occurs among men with AIDS wasting.\n To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting.\n Randomized, controlled trial.\n University hospital.\n 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%).\n In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks.\n Cross-sectional muscle area and other indices of muscle mass.\n Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052).\n In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.", "We examined the effects of chronic exercise on fitness and immune status in Caucasian males (34.9 +/- 5.6 yr) diagnosed by Western blot as seropositive for the HIV-1 virus. The exercise regimen involved 12 wk of 1 h sessions 3 d.wk: 20 min of cycle exercise at 60-80% HRreserve was followed by 35 min of strength and flexibility training. After matching subjects on health status (modified Walter Reed criteria), subjects (N = 37) were randomly assigned to exercise or a counseling control condition. Changes in strength, responses to the YMCA cycle test, and serum lymphocytes were tested by MANOVA in a condition (exercise or counseling)-by-time (pretest, posttest) design with repeated measures on time. Results indicated significant (P less than 0.001) group-by-time interactions for strength (N.m) (chest press and leg extension) and for HR (beats.min-1) and total time (TT) on the cycle test at 150 W. Strength and TT increased and HR decreased in the exercise condition, while control subjects did not change. Total leukocyte, lymphocyte, CD4+, and CD8+ cell counts, and the CD4+/CD8+ ratio were statistically unchanged for each condition. We conclude that HIV-1+ men, including those symptomatic for AIDS-related complex, can experience significant increases in neuromuscular strength and cardiorespiratory fitness without changes in lymphocyte phenotypes or clinical diagnosis when the exercise regimen is prescribed and monitored in accordance with ACSM guidelines for healthy adults.", "Women infected with human immunodeficiency virus (HIV) increasingly demonstrate abnormalities in fat distribution and metabolism; however, the effects of a home-based exercise regimen in this group have not been investigated.\n We conducted a 16-week randomized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution. Cross-sectional muscle area and muscle attenuation were measured by computed tomography. Cardiorespiratory fitness was determined by calculated maximum oxygen consumption (VO2max) and strength by 1-repetition maximum.\n Cardiorespiratory fitness (VO2max) was markedly lower at baseline (median [95% confidence interval], 15.4 [8.3-25.2] mL x kg(-1) x min(-1)) than reported values for healthy female subjects (26-35 mL x kg(-1) x min(-1)). Subjects randomized to exercise had significant improvement in mean +/- SEM VO2max (1.5 +/- 0.8 vs -2.5 +/- 1.6 mL x kg(-1) x min(-1); P<.001) and endurance (1.0 +/- 0.3 vs -0.6 +/- 0.3 minute; P<.001). Strength increased at the knee extensors, pectoralis, knee flexors, shoulder abductors, ankle plantar flexors, and elbow flexors (all P<.001). Total muscle area (6 +/- 1 vs 2 +/- 1 cm2; P = .02) and attenuation (2 +/- 1 vs -1 +/- 1 Hounsfield unit; P = .03) increased in the exercise group. No significant difference was seen in lipid levels, blood pressure, or abdominal visceral fat between the groups, but subjects randomized to exercise reported improved energy and appearance.\n A 16-week, supervised, home-based exercise regimen improved measures of physical fitness in HIV-infected women. The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen.", "We attempted to measure cardiopulmonary effects, CD4 counts, and perceived sense of well-being in 25 individuals moderately to severely immunocompromised from HIV infection (mean entry CD4 count = 144.microliters-1) before and after a 24-wk program of exercise training. Only six subjects completed the 24-wk program. All six showed evidence of a training effect. Statistically significant improvements were seen in maximal oxygen consumption (VO2max), oxygen pulse, and minute ventilation. Submaximal exercise performance improved significantly by 12 wk in the 10 individuals available for testing: decreases were seen in heart rate, rate pressure product, and rate of perceived exertion. White blood cell counts and T-lymphocyte subsets were stable at 12 and 24 wk in the subjects available for testing. High depression/anxiety scores on a mental health inventory (General Health Questionnaire) correlated with low CD4 counts. Scores did not correlate with compliance with the exercise program. There was a trend (P < 0.10) for scores to improve over time among those individuals who attended > or = 80% of scheduled exercise sessions. We conclude that exercise training is feasible and beneficial for some HIV-infected individuals.", "The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200-499 x 106 CD4+ cells/l).\n The study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment.\n Sixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program.\n At baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups.\n We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.", "HIV-infected individuals are frequently active, but guidelines for exercise in this population lack scientific support, since studies on the effects of exercise training on immunologic variables of HIV-1 positive individuals have shown conflicting results. Exercise capacity, immunologic markers (CD4, CD8 and CD4:CD8 ratio), anthropometric measurements, and depression scores were evaluated to compare the effects of two intensities of aerobic exercise on HIV-1 seropositive individuals. Twenty-one healthy subjects (14 men, 7 women), carriers of the HIV-1 virus (CD4>200 cells x mm(-3)), and inactive for at least 6 months, completed a 12 week exercise training program (36 sessions of 1 h, 3 times per week), in a moderate intensity group (60+/-4% of maximal heart rate) or a high intensity group (84+/-4% of maximal heart rate). Exercise capacity estimated by treadmill time was increased significantly in both moderate intensity (680+/-81 s before; 750+/-151 s after) and high intensity (651+/-122 s before; 841+/-158 s after) groups, but the high intensity group presented a significantly larger increment (p<0.01). There were no significant changes in the immunologic variables, anthropometric measurements or depression scores. Thus, HIV-seropositive individuals that participate in moderate and high intensity exercise programs are able to increase their functional capacity without any detectable changes in immunologic variables, anthropometric measurements or depression scores.", "Our objective was to examine the effects of exercise training (EXS) on quality of life (QoL) in highly active antiretroviral therapy (HAART)-treated HIV-positive (HIV+) subjects with body fat redistribution (BFR) in Rwanda.\n The effects of a randomised controlled trial of EXS on QoL were measured using World Health Organisation Quality of Life (WHOQOL)-BREF in HIV+ subjects with BFR randomised to EXS (n = 50; BFR + EXS) or no exercise training (n = 50; BFR + noEXS).\n At 6 months, scores on the psychological [1.3 (0.3) vs. 0.5 (0.1); P < 0.0001], independence [0.6 (0.1) vs. 0.0 (0.0); P < 0.0001], social relationships [0.6 (0.2) vs. 0.0 (0.0); P < 0.0001] and HIV HAART-specific QoL domains [1.4 (0.2) vs. -0.1 (0.2); P < 0.0001] improved more in BFR + EXS than BFR + noEXS group, respectively. Self-esteem [1.3 (0.8) vs. 0.1 (0.6); P < 0.001], body image [1.5 (0.6) vs. 0.0 (0.5); P < 0.001] and emotional stress [1.6 (0.7) vs. 0.2 (0.5); P < 0.001] improved more in the BFR + EXS group than BFR + noEXS group, respectively. Psychological [1.5 (0.2) vs. 1.1 (0.3); P < 0.0001], social relationship [0.8 (0.2) vs. 0.4 (0.2); P < 0.0001], and HIV HAART-specific well-being [1.8 (0.2) vs. 1.0 (0.0); P < 0.0001] improved more in BFR + EXS female than male subjects.\n Exercise training improved several components of QoL in HAART-treated HIV+ African subjects with BFR. Exercise training is an inexpensive and efficacious strategy for improving QoL in HIV+ African subjects, which may improve HAART adherence and treatment initiatives in resource-limited areas of sub-Saharan Africa.", "The impact of aerobic exercise training as a buffer of the affective distress and immune decrements which accompany the notification of HIV-1 antibody status in an AIDS risk group was studied. Fifty asymptomatic gay males with a pretraining fitness level of average or below (determined by predicted VO2 max) were randomly assigned to either an aerobic exercise training program or a no-contact control condition. After five weeks of training, at a point 72 hours before serostatus notification, psychometric, fitness and immunologic data were collected on all subjects. Psychometric and immunologic measures were again collected one-week postnotification. Seropositive controls showed significant increases in anxiety and depression, as well as decrements in natural killer cell number following notification whereas, seropositive exercisers showed no similar changes and in fact, resembled both seronegative groups. These findings suggest that concurrent changes in some affective and immunologic measures in response to an acute stressor might be attenuated by an experimentally manipulated aerobic exercise training intervention.", "The authors conducted a randomized controlled trial to assess the impact of a 15-week (20 minutes three times per week) home-based aerobic exercise intervention versus usual care on the physical endurance, immune status, and self-reported health status of 99 HIV-infected adults. In the exercise group, there was no improvement in physical endurance or health-related quality of life (HRQOL), except in the Medical Outcomes Study-HIV Health Survey Overall Health subscale (difference = 12.1, 95% confidence interval = 2.0-22.2, p = .02). Although physical endurance levels were maintained at baseline levels in the intervention group and declined in the control group, differences between the groups were small and not significant. There were also no significant changes in CD4+ T-lymphocyte counts. Exercise appears to be safe in HIV-infected patients. Improvements in physical endurance and HRQOL might result if the exercise protocol is longer or progressive. Further research is needed to establish guidelines for exercise in patients on highly active antiretroviral therapy.", "The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse.\n Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded.\n Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05).\n We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.", "To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients.\n We conducted a prospective, randomized, 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution. Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week. Cardiovascular parameters, including blood pressure and endurance during sub-maximal stress testing, body composition, strength, insulin and other biochemical parameters were determined.\n Thirty-seven patients were randomized and 25 subjects completed the study. Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [-0.02 (-0.06, -0.01) (median (interquartile range) versus -0.01 (0.03, 0.02), P = 0.026], resting systolic [-12 (-20, -4) versus 0 (-11, 11), P = 0.012] and diastolic blood pressures [-10 (-14, -8) versus 0 (-7, 8), P = 0.001], increased thigh muscle cross-sectional area [3 (-3, 12) versus -7 (-11, 0), P = 0.015], and improved exercise time [3 (0, 4) versus 0 (-1, 1), P = 0.045] compared with subjects receiving metformin alone. Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05). Lipids and resting lactate did not change significantly between treatment groups.\n These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia. Combined treatment was safe, well tolerated and may be a useful strategy to decrease cardiovascular risk in this population.", "Highly active antiretroviral therapy has improved the prognosis of human immuno deficiency virus type 1 (HIV-1)-infected individuals, but it has been associated with the development of metabolic and fat distribution abnormalities known as the lipodystrophy syndrome. This study tested the hypothesis that aerobic exercise training added to a low-lipid diet may have favorable effects in HIV-1-infected individuals with dyslipidemia and lipodystrophy.\n Thirty healthy subjects, carriers of HIV-1, with dyslipidemia and lipodystrophy, all of whom were using protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors, were randomly assigned to participate in either a 12-wk program of aerobic exercise or a 12-wk stretching and relaxation program. All subjects received recommendations for a low-lipid diet. Before and after intervention, peak oxygen uptake, body composition, CD4, viral load, lipid profile, and plasma endothelin-1 levels were measured.\n Peak oxygen uptake increased significantly in the diet and exercise group (mean +/- SD: 32 +/- 5 mL x kg(-1) x min(-1) before; 40 +/- 8 mL x kg(-1) x min(-1) after) but not in the diet only group (34 +/- 7 mL x kg(-1) x min(-1) before; 35 +/- 8 mL x kg(-1) x min(-1) after). Body weight, body fat, and waist-to-hip ratio decreased significantly and similarly in the two groups. There were no significant changes in immunologic variables in either group. Likewise, plasma triglycerides, total cholesterol, and HDL cholesterol levels did not change significantly in either group. Plasma endothelin-1 levels were elevated in both groups and presented no significant changes during the study.\n HIV-seropositive individuals with lipodystrophy and dyslipidemia submitted to a short-term intervention of low-lipid diet and aerobic exercise training are able to increase their functional capacity without any consistent changes in plasma lipid levels." ]

[ "363236", "2540285", "707035", "4571680", "16099630" ]

[ "Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis.", "A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis.", "Linoleic acid in multiple sclerosis: failure to show any therapeutic benefit.", "Double-blind trial of linoleate supplementation of the diet in multiple sclerosis.", "Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients." ]

[ "One hundred and sixteen patients with acute remitting multiple sclerosis (MS) took part in a double-blind controlled trial of treatment with polyunsaturated fatty acids and were randomly allocated to one of four groups. Two groups received linoleic acid, one alone as a spread and one with gamma-linolenic acid in capsules (Naudicelle); and two control groups received oleic acid, one as a spread and one in capsules. Rates of clinical deterioration and frequencies of attacks were not significantly different between treated and control groups. Exacerbations were shorter and less severe in patients receiving a high dose of linoleic acid than in controls, but those receiving a lower dose--that is, Naudicelle--showed no such difference. Thus supplementing the diet with 20 g linoleic acid marginally affected the duration and severity of relapses of MS but had no effect on overall disability. The dose of Naudicelle used provided insufficient supplementation.", "A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period. Ambulant patients (312) with acute remitting disease were randomly allocated to treatment or placebo. Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids. Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration, frequency and severity of relapses and the number of patients who had improved or remained unchanged. The results showed no significant difference at the usual 95% confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined.", "We have studied the effect of a dietary supplement with linoleic acid (LA) in 76 patients with MS. We could detect no effect of this supplement on the progression of neurological findings, the relapse rate, or the severity of relapses. We were also able to show that oral supplementation with a linoleic acid preparation would raise the blood level of LA in these patients. We were unable to show that there was any reduction in the linoleic acid blood levels associated with acute relapses of MS during this study.", "Seventy-five patients in London and Belfast with multiple sclerosis were given daily supplements of a vegetable oil mixture containing either linoleate or oleate for two years in a double-blind control trial. Relapses tended to be less frequent and were significantly less severe and of shorter duration in the linoleate-supplemented group than in those receiving the oleate mixture, but clear evidence that treatment affected the overall rate of clinical deterioration was not obtained.", "To determine whether a low fat diet supplemented with omega-3 positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial, patients were randomized to two dietary interventions: the \"Fish Oil\" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the \"Olive Oil\" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was the Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires, neurological status and relapse rate were obtained.\n 31 RRMS patients were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050) at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The relapse rate decreased in both groups relative to the rates during the 1 year preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies." ]

[ "2513939", "3484773", "6499513", "1337623", "4081404", "10225575", "1929311", "2906171", "1310715", "6269263", "3563430", "10440621", "2291755", "6604266", "8471899", "11820968", "2003341", "6794832", "10724022", "1638586", "4002410", "3310941", "6887360", "7202832", "6396834", "9064058", "6245976", "3887560" ]

[ "Different lengths of treatment with co-trimoxazole for acute uncomplicated urinary tract infections in women.", "Randomized study of single-dose, three-day, and seven-day treatment of cystitis in women.", "Comparative efficacy of 3-day and 7-day chemotherapy with twice-daily pivmecillinam in urinary tract infections seen in general practice.", "Lomefloxacin versus norfloxacin in the treatment of uncomplicated urinary tract infections: three-day versus seven-day treatment. The South Swedish Lolex Study Group.", "Nalidixic acid and pivmecillinam for treatment of acute lower urinary tract infections.", "A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection.", "Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women.", "Double-blind comparison of 3-day versus 7-day treatment with norfloxacin in symptomatic urinary tract infections. The Inter-Nordic Urinary Tract Infection Study Group.", "Comparison of three-day temafloxacin with seven-day ciprofloxacin treatment of urinary tract infections in women.", "[Pivmecillinam (Selexid) in acute cystitis. A comparative study of 3- and 7-day treatments].", "Comparison of three- and ten-day regimens with a sulfadiazine-trimethoprim combination and pivmecillinam in acute lower urinary tract infections.", "Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women. Sparfloxacin Multicenter Uncomplicated Urinary Tract Infection Study Group.", "Pivmecillinam treatment in acute cystitis. Three versus seven days study.", "Acute cystitis in young women. Treatment with citrated nalidixic acid compared with co-trimoxazole.", "Treating acute urinary tract infections. An RCT of 3-day versus 7-day norfloxacin.", "[Urinary infections without complications: comparison of a treatment with norfloxacin for 7 days versus norfloxacin for 3 days].", "Randomized study to evaluate efficacy and safety of ofloxacin vs. trimethoprim and sulfamethoxazole in treatment of uncomplicated urinary tract infection.", "Treatment of acute urinary tract infection with three doses of co-trimoxazole.", "Comparison of pivmecillinam and cephalexin in acute uncomplicated urinary tract infection.", "Ofloxacin versus trimethoprim/sulfamethoxazole in the treatment of uncomplicated urinary tract infection.", "[Treatment of acute urinary infections. Comparison between pivmecillinam for 3 days and sulfamethizole therapy for 6 days].", "A multicenter comparative trial of three-day norfloxacin vs ten-day sulfamethoxazole and trimethoprim for the treatment of uncomplicated urinary tract infections.", "Treatment of urinary tract infections with varying regimens of sulfisoxazole.", "A comparison of a 3-day course of Mictral with a 7-day course of ampicillin in the treatment of urinary tract infection.", "A randomised comparison of single-dose vs. three-day and ten-day therapy with trimethoprim-sulfamethoxazole for acute cystitis in women.", "[Treatment of uncomplicated recurrent cystitis in women: lomefloxacin versus norfloxacin].", "Comparative efficacy of 3-day and 7-day chemotherapy with pivmecillinam in urinary tract infections in general practice.", "Cefadroxil once daily for three or seven days versus amoxycillin for seven days in uncomplicated urinary tract infections in women." ]

[ "To compare three days' and seven days' treatment with co-trimoxazole in women with acute dysuria, strangury, and urinary frequency or urgency.\n Randomised double blind placebo controlled trial.\n General practices in the south east of The Netherlands.\n 327 Non-pregnant female patients aged 12 to 65.\n 161 Women were allocated to three days' treatment (co-trimoxazole 960 mg twice a day), and 166 women were allocated to seven days' treatment (co-trimoxazole 960 mg twice a day).\n Resolution of symptoms at one, two, and six weeks.\n The rates for resolution of symptoms were not significantly different between the two groups. Cumulative rates of recurrence after three days' and seven days' treatment were 31/139 (22%) and 23/151 (15%) respectively six weeks after entry (p = 0.16). Adverse effects occurred in a quarter of women given three days' treatment compared with a third of women receiving seven days' treatment (p = 0.29). In only two patients did adverse effects necessitate stopping treatment.\n Three days of co-trimoxazole seems to be as effective as a seven days' course for treating acute urinary tract infection in non-pregnant women.", "We evaluated the following five treatment regimens for acute cystitis in nonpregnant women: cefadroxil, 1,000 mg single-dose; cefadroxil, 500 mg twice a day for three days; cefadroxil, 500 mg twice a day for seven days; trimethoprim-sulfamethoxazole (TMP-SMZ), 320-1,600 mg single-dose, and TMP-SMZ, 160-800 mg twice a day for three days. At four weeks after the end of treatment, 25%, 58%, 70%, 65%, and 88% of patients, respectively, remained cured of infection. The results indicated that three-day treatment (1) might improve cure rates (over single-dose), (2) would reduce incidence of relapse (vs. single-dose), and (3) may be as curative as seven-day treatment. The results of the antibody-coated bacteria test did not predict treatment failure or relapse.", "In a multi-centre general practice study, 183 females suffering from symptoms of acute urinary tract infection were randomly assigned to receive 400 mg pivmecillinam twice-daily for either 3 or 7 days. The clinical response was equally good in both treatment groups with a mean reduction in symptom scores of 88%. Positive pre-treatment bacteriological cultures were obtained from 48 (36%) of the 134 patients for whom data were complete. Bacteriological cure was achieved in all these patients except for 1 in the 3-day treatment group. Pivmecillinam was well tolerated, with side-effects reported by 7 (7%) patients in the 3-day group and 12 (13%) patients in the 7-day group. One patient in the 3-day group and 2 patients in the 7-day group stopped treatment prematurely due to side-effects.", "This randomised, double-blind, multicenter study compared the safety and efficacy of lomefloxacin and norfloxacin in adult female outpatients with uncomplicated urinary tract infections. Patients were randomly assigned to one of 3 treatment groups: 400 mg lomefloxacin once daily for 3 days (L3), 400 mg lomefloxacin once daily for 7 days (L7), or 400 mg norfloxacin twice daily for 7 days (N7). A total of 703 patients (age 17-75 years) were enrolled at 21 investigative sites in southern Sweden. Clinical and microbiological evaluations were conducted at the start, 5-9 days and 3-4 weeks post therapy. Patients with quantitative urine cultures of > or = 10(4) CFU/ml of a susceptible pathogen were considered evaluable for efficacy. Escherichia coli and Staphylococcus saprophyticus were the most commonly isolated pathogens. In both L3 and L7 groups, 196 patients and in the N7 group 195 patients met the criteria for efficacy evaluation. At the 5-9 day post-treatment evaluation, 88% of the pathogens were eradicated in the L3 group, 93% in the L7 group and 93% in the N7 group. At the 3-4 week post-treatment evaluation, 81%, 82%, and 85% of urine cultures remained negative in the L3, L7, and N7 groups, respectively. No statistically significant differences between the 3 treatment groups were noted with the exception of eradication of S. saprophyticus, for which the 7 day courses were more effective at 4-9 days post treatment. No persistent pathogen developed resistance to the study drugs. All 3 treatment regimens were equally well tolerated, except for photosensitivity reactions, which were more frequently reported in patients in the lomefloxacin groups.", "Women, 15-45 years of age, with symptoms of lower urinary tract infection (UTI) were randomly treated with nalidixic acid (1 g X 3) or pivmecillinam (200-400 mg X 3) for three or seven days, respectively. Therapeutic failure, relapse, or reinfection occurred among 18% of 82 women, even though the isolated strains of gram-negative rods in these patients were susceptible in vitro to the antibiotics used. Therapeutic failure, i.e. no effect or at best only a minor effect on the symptoms, was registered in 10 of 13 cases of UTI caused by Staphylococcus saprophyticus and treated with nalidixic acid, which was consistent with the high minimum inhibitory concentrations (MIC) (128-512 micrograms/ml) of this antibiotic. S. saprophyticus was isolated in 9 of 12 patients during treatment with nalidixic acid. On the other hand, pivmecillinam therapy was clinically effective in 16 of 18 patients with UTI caused by S. saprophyticus, even though the MIC of mecillinam to these strains was considerably higher (8-64 micrograms/ml) than that vis-à-vis gram-negative rods. Thus the clinical effect of pivmecillinam was significantly better than that of nalidixic acid in cases of UTI caused by S. saprophyticus. The organism was not isolated from 14 patients receiving pivmecillinam therapy.", "The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4-10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = -20.6%, -3.9%) and nitrofurantoin (82%; 95% CL = -17.1%, -0.9%). Clinical resolution 4-10 days after therapy and at the 4-6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P = 0.093) among the three drug regimens, although co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P < or = 0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P < or = 0.01).", "We compared the safety and efficacy of a single 400-mg dose of ofloxacin, ofloxacin (200 mg) once daily for 3 days, and trimethoprim-sulfamethoxazole (160:800 mg) twice daily for 7 days for the treatment of acute uncomplicated cystitis (urinary tract infection [UTI]) in women. At 5 weeks posttreatment, 35 (81%) of 43 patients treated with single-dose ofloxacin, 40 (89%) of 45 treated with 3 days of ofloxacin, and 41 (98%) of 42 treated with trimethoprim-sulfamethoxazole were cured (P = 0.03, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). Retreatment for symptomatic recurrent UTI was given to 7 (16%) of 43 patients initially treated with single-dose ofloxacin, 3 (7%) of 45 patients treated with 3 days of ofloxacin, and 0 of 42 patients treated with trimethoprim-sulfamethoxazole (P = 0.01, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). There was a trend in each of the three treatment groups toward an association between persistent or recurrent episodes of significant bacteriuria and a history of UTI in the past year and with diaphragm use. Ofloxacin was more effective than trimethoprim-sulfamethoxazole in eradicating Escherichia coli from rectal cultures during or soon after therapy, but there were no differences at later follow-up visits. Adverse effects were equally common among the three treatment groups. We conclude that single-dose ofloxacin was less effective than 7 days of trimethoprim-sulfamethoxazole for treatment of uncomplicated cystitis in women, while the 3-day ofloxacin regimen and the trimethoprim-sulfamethoxazole regimen were not significantly different in efficacy.", "The therapeutic efficacy and safety of norfloxacin 400 mg twice daily for 3 or 7 days was compared in a double-blind randomized multiclinic study including 485 female general practice patients with uncomplicated symptomatic lower urinary tract infections. 373 patients were considered valid for efficacy, 193 in the 3-day treatment group and 180 in the 7-day treatment group. The short-term efficacy (elimination of significant bacteriuria 3-13 days post-treatment) was 93.8% and 96.6% in the 3 and 7-day treatment groups, respectively, and the accumulated efficacy (elimination of significant bacteriuria 3 days post-treatment up until 45 days after the first dose) 81.3% and 91.7%, respectively (p less than 0.004). The median time to disappearance of symptoms was 3 days in both groups. Norfloxacin was well tolerated in both treatment groups.", "Temafloxacin is a new broad-spectrum arylfluoroquinolone antimicrobial with an extended serum half-life.\n In this large, multicenter, double-blind clinical trial, 404 women with acute, uncomplicated urinary tract infections (UTI) were randomized to receive temafloxacin 400 mg once daily for 3 days, or ciprofloxacin 250 mg twice daily for 7 days. Clinical and microbiologic evaluations were repeated at 4 to 5 days after initiation of treatment, at the end of therapy, and at 5 to 9 days posttreatment. One hundred fifteen patients who received temafloxacin and 105 patients who received ciprofloxacin met the eligibility criteria for efficacy evaluation. The predominant urinary pathogens were Escherichia coli, Proteus mirabilis, and coagulase-negative staphylococci. No pretherapy isolate was resistant to either study drug.\n Bacteriologic eradication was observed in 112 (97%) of 115 women treated with temafloxacin and 101 (96%) of 105 women treated with ciprofloxacin. Clinical cure rates at 5 to 9 days posttreatment were 90% (the remaining 10% improved) with temafloxacin and 95% (the remaining 5% improved) with ciprofloxacin. Adverse effects associated with treatment occurred in 24 (12%) women who received temafloxacin and 31 (15%) women who received ciprofloxacin. Headache (2% with temafloxacin and 2% with ciprofloxacin), nausea (3% with temafloxacin and 6% with ciprofloxacin), and somnolence (4% with temafloxacin and 3% with ciprofloxacin) were reported most often. Only three and five patients who were treated with temafloxacin and ciprofloxacin, respectively, discontinued treatment because of adverse effects.\n In this study, a 3-day treatment regimen using a single daily 400-mg dose of temafloxacin was found to be as effective as a 7-day course of ciprofloxacin in women with acute uncomplicated UTI.", "nan", "132 female hospital employees (mean age 32 years) with uncomplicated, bacteriologically verified acute lower urinary tract infection were included in a randomized study. The patients were treated for 3 or 10 days with a sulfadiazine-trimethoprim combination (500 mg + 150 mg) b.i.d. or for 3 or 10 days with pivmecillinam (500 mg) t.i.d. The first follow-up evaluation was performed 3-5 days after the treatment. In both sulfadiazine-trimethoprim groups the cure rate was 97% and in both pivmecillinam groups 80%. This difference was mainly due to the occurrence of pivmecillinam-resistant Staphylococcus saprophyticus strains. 109 patients attended the second follow-up visit about 4 weeks after treatment. The prevalences of reinfections and relapses were 18% in both 3-day regimens and 4-7% in both 10-day regimens. No side-effects were reported in the 3-day sulfadiazine-trimethoprim group, while about 20% in the corresponding 10-day group had side-effects. Side-effects were not common in patients treated with pivmecillinam.", "Urinary tract infection (UTI) is a common illness, with > or =30% of all women experiencing a UTI during their lifetime. Less than a decade ago, the standard therapy for acute uncomplicated UTIs involved treatment with > or =7 days of an antibacterial agent, but recent studies using a variety of newly introduced antibiotics, including the fluoroquinolones, have demonstrated that a 1- to 5-day treatment regimen can be equally effective. This randomized, double-masked, multicenter study was conducted to compare the efficacy and tolerability of a single dose of sparfloxacin with those of a 3-day regimen of sparfloxacin and a 7-day regimen of ciprofloxacin in the treatment of women with community-acquired acute uncomplicated urinary tract infection. A total of 1175 women were enrolled; 395 received sparfloxacin as a single 400-mg dose on day 1, 394 received sparfloxacin as a 400-mg loading dose on day 1 followed by 200 mg once daily for 2 additional days, and 386 received ciprofloxacin 250 mg twice daily for 7 days. Patients were comparable with respect to demographic characteristics and underlying conditions. A total of 954 patients were clinically assessable; 490 of these were also bacteriologically assessable. All patients treated were included in the tolerability analysis. Escherichia coli (75.4%), Klebsiella pneumoniae (4.9%), Enterococcus faecalis (4.6%), and Staphylococcus saprophyticus (4.1%) were the most commonly isolated organisms. In the all-treated population, clinical success was achieved 5 to 9 days after therapy in 91.8%, 92.2%, and 91.6% of patients in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; bacteriologic success was observed in 91.7%, 92.6%, and 96.6% of those in the 3 groups. Sustained clinical success rates 4 to 6 weeks after therapy were 76.6%, 80.2%, and 79.5% in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; sustained bacteriologic success rates were 80.7%, 90.1%, and 92.6%. The most common adverse events were nausea, headache, vaginal thrush, dizziness, and diarrhea; >92% of adverse events were mild or moderate in severity. The 2 drugs had comparable frequencies of adverse events, except for photosensitivity, which occurred in 3.3% of the 3-day sparfloxacin group, 1.3% of the single-dose sparfloxacin group, and 0.3% of the ciprofloxacin group (P = 0.005). The 3-day sparfloxacin regimen was effective and well tolerated. The initial response to single-dose sparfloxacin treatment was comparable to the response to the other 2 regimens, but the single-dose regimen proved less effective over time, with higher rates of clinical recurrence and bacteriologic relapse. Sparfloxacin provides an alternative to ciprofloxacin for patients with acute uncomplicated urinary tract infection who are not at risk for photosensitivity reactions or adverse events associated with a prolonged corrected QT interval.", "In an open randomized study pivmecillinam (Selexid; CAS 32886-97-8) was studied by general practitioners in 345 female patients with uncomplicated acute cystitis. Out of the bacteriologically evaluated 299 patients 151 patients were treated for three days with two tablets of pivmecillinam 200 mg t.i.d. and 148 patients for seven days with one tablet t.i.d. There were no significant differences in the bacteriological effect between the two regimens. In the 3-day group 91% and 88% were cured at the first and the second control; in the 7-day group 94% and 95%, respectively. There was no significant difference in the total clinical effect, either. Adverse reactions, usually gastrointestinal disturbances, occurred in 10% of the 3-day group and in 11% of the 7-day group (N.S.). Pivmecillinam treatment in acute cystitis in women was equally effective whether given for three or seven days, with the same total frequency of adverse reactions for the two regimens.", "nan", "A randomized, controlled trial was carried out to compare two courses of treatment in women with acute urinary tract infection in general practice. The 3-day course of treatment was found to be as effective as, and cheaper than, the 7-day therapy.", "nan", "The efficacy and safety of ofloxacin taken orally once a day for three days was compared with a combination of trimethoprim and sulfamethoxazole (TMP/SMX) taken orally twice a day for seven days in the treatment of uncomplicated urinary tract infection. The diagnosis was established by the presence of symptoms including dysuria, frequency, suprapubic pain, and urgency. Bacteriuria was confirmed by a urine culture of a minimum of 10(5) organisms per mL, of at least one species. A treatment course of ofloxacin, once-a-day for three days, was as safe and effective as a standard course of TMP/SMX, twice a day for seven days.", "nan", "The clinical and bacteriological efficacy of a 3-day course of pivmecillinam, 200 mg three times daily, was compared with that of a 7-day course of cephalexin, 250 mg four times daily, in 216 patients with a bacteriologically confirmed, acute, uncomplicated, urinary tract infection. Both treatments were similarly effective. Clinical cure or improvement was obtained in 95.3% of patients given pivmecillinam and in 93.6% of patients given cephalexin. Bacteriological success was achieved in 89.7 and 81.7% patients taking pivmecillinam or cephalexin, respectively. Eradication rates for Escherichia coli were 90.1% for pivmecillinam and 80.6% for cephalexin. Both treatments were well tolerated. This study has confirmed that a 3-day course of pivmecillinam is effective and well tolerated in uncomplicated cystitis.", "A multicenter randomized study was conducted to compare the efficacy and safety of ofloxacin with that of trimethoprim/sulfamethoxazole (TMP/SMX) in the treatment of uncomplicated urinary tract infection in adults. Patients were randomized to receive either oral ofloxacin 200 mg daily for three days (102 patients), or oral TMP/SMX 160 mg/800 mg twice daily for seven days (100 patients). The pathogen was eradicated in 73 (97.3%) of the 75 evaluable patients receiving ofloxacin and in 66 (97.1%) of the 68 evaluable patients receiving TMP/SMX. The most frequently isolated pathogens were Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. More urinary pathogens were susceptible to ofloxacin than to TMP/SMX, although this difference was not statistically significant. The clinical cure rate for patients receiving ofloxacin was 93.3%, with 4% improved and 2.7% failed. For patients receiving TMP/SMX, the clinical cure rate was 86.4%, with 12.1% improved and 1.5% failed. Side effects were reported by 29.7% of the patients receiving ofloxacin and by 40.4% of the patients receiving TMP/SMX. Drug-related adverse experiences, as determined by the investigators, occurred in 5% of the ofloxacin patients and in 15.2% of the TMP/SMX patients, a statistically significant difference. No patients receiving ofloxacin, compared with three patients receiving TMP/SMX, discontinued therapy because of an adverse reaction. These results indicate that short-course ofloxacin is as effective as TMP/SMX in the treatment of uncomplicated urinary tract infection. Ofloxacin therapy is also better tolerated than TMP/SMX.", "nan", "Two-hundred nine patients with symptoms of acute urinary tract infection and pyuria were randomized to 400 mg of administered norfloxacin twice daily for three days, or 800 mg of sulfamethoxazole and 160 mg of trimethoprim administered twice daily for ten days. Therapeutic outcome was assessed five to nine days and four to six weeks after treatment. The cure rates were 71/74 (96%) with norfloxacin and 81/81 (100%) with sulfamethoxazole and trimethoprim five to nine days after treatment. Only seven patients had a recurrence at the second follow-up visit; four in the norfloxacin group and three in the sulfamethoxazole and trimethoprim group. No isolates were resistant to norfloxacin, but three Escherichia coli were resistant to sulfamethoxazole and trimethoprim. Fifteen patients in each group reported a side effect during treatment. Two patients in the norfloxacin group and four patients in the sulfamethoxazole and trimethoprim group discontinued therapy due to an adverse effect. In this multicenter study, a three-day course of norfloxacin was as effective and safe as a ten-day regimen of sulfamethoxazole and trimethoprim in the treatment of acute uncomplicated urinary tract infections.", "Four therapeutic regimens of sulfisoxazole were compared and contrasted with the antibody-coated bacteria test in patients with acute urinary tract infections. Of 158 college coeds who entered the study 146 completed the randomly assigned regimen. All 146 patients received 2 gm. sulfisoxazole initially and 1 gm. 4 times daily for 3 days in 44 patients (group 1), 7 days in 51 (group 2), 14 days in 29 (group 3) and 21 days in 22 (group 4). The presumptive sites of infection by the antibody-coated bacteria test were kidney (positive test) in 43 per cent of the patients and bladder (negative test) in 51.3 per cent. There was no correlation between the results of the antibody-coated bacteria test with either the presenting symptoms or the therapeutic responses. The bacteriologic cure rates at 2 days after therapy were 100 per cent in all groups and at 4 weeks after therapy they were 88.6 per cent in group 1, 86.3 per cent in group 2, 86.2 per cent in group 3 and 91 per cent in group 4. A 3-day course of sulfisoxazole was as effective as the longer regimens.", "This general practice study compared a 3-day course of a new preparation, Mictral, with a standard 7-day course of ampicillin in the treatment of uncomplicated urinary tract infection. Mictral achieved bacteriological cure in all infected patients by Day 4 while only 69% of infected patients in the ampicillin group were abacteriuric by Day 8. Symptomatic relief and the incidence of side-effects were similar for both groups. It is concluded that Mictral appears to be a useful addition to currently available therapy for urinary tract infection and merits further investigation.", "The efficacy of a single-dose (4 tablets) trimethoprim-sulfamethoxazole (TMP-SMX) was compared with that of a 3-day and 10-day treatment with TMP-SMX, 2 tablets twice daily, in 464 female out-patients with symptoms denoting acute, uncomplicated urinary tract infection (UTI). 321 patients (70%) had significant bacteriuria. Treatment effect could be assessed in 279 women. Comparable results were obtained with the 3 regimens 2 and 6 weeks after treatment. Eradication of the initial organism occurred in 96% with single-dose, in 96-94% with a 3-day, and in 98% with a 10-day course. The incidence of adverse reactions was significantly greater in patients treated with a 10-day (28%) than in those treated with a single-dose (5%), or 3-day (9%) regimen (p less than 0.01). This study suggests that short treatment regimens for uncomplicated UTI in women are as effective as and cause fewer side-effects than the conventional 10-day chemotherapy.", "compare the acceptability of 3-day regimen with that of 10-day regimen of fluoroquinolones for the treatment of recurrent uncomplicated lower urinary tract infection in women.\n a multicentric, randomized open trial was conduced in 421 patients by gynecologic and general practitioners to determine acceptability, efficacy and safety of lomefloxacin 400 mg in a once a day dose given for three days compared with norfloxacin 800 mg in twice a day dose given for ten days for the treatment of recurrent uncomplicated lower urinary tract infection in women.\n acceptability, assessed at day 14, was significantly better for lomefloxacin group than norfloxacin group, respectively 57,1 p.100 and 38,0 p.100. Clinical success rate at day 14 was 97,2 p.100 for lomefloxacin and 97,5 p.100 for norfloxacin; at day 30 clinical success rate was respectively 97,6 p.100 and 98,1 p.100 relapse at one year was comparable between two groups. Adverse events were reported respectively in 15,6 p.100 and 16,6 p.100 of the patients, vaginal infections, dermatologic disorders and digestive disorders (abdominal pain, nausea) predominated. There were no serious adverse event.\n the acceptability is better for a 3-day regimen of lomefloxacin than a 10-day regimen of norfloxacin for treatment of recurrent uncomplicated lower urinary tract infection in women for comparable efficacy and safety.", "nan", "The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group." ]

[ "11389408", "1826175", "9761803", "2139241", "8235809", "9253097", "10457579", "14560075" ]

[ "Long-term effects of specific stabilizing exercises for first-episode low back pain.", "Effects of an exercise program on sick leave due to back pain.", "A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.", "Conservative treatment of acute low-back pain. A prospective randomized trial: McKenzie method of treatment versus patient education in \"mini back school\".", "A randomized, placebo-controlled trial of exercise therapy in patients with acute low back pain.", "Effect of exercise on sick leave due to low back pain. A randomized, comparative, long-term study.", "The effect of a Mensendieck exercise program as secondary prophylaxis for recurrent low back pain. A randomized, controlled trial with 12-month follow-up.", "Does early intervention with a light mobilization program reduce long-term sick leave for low back pain: a 3-year follow-up study." ]

[ "A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups.\n To report a specific exercise intervention's long-term effects on recurrence rates in acute, first-episode low back pain patients.\n The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term.\n Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients.\n Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P < 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P < 0.01).\n Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone.", "The purposes of this study were to evaluate the effect of a weekly exercise program on short-term sick leave (less than 50 days) attributable to back pain and to determine whether changes in absenteeism were related to changes in cardiovascular fitness. Subjects were randomly assigned to an exercise group (n = 58) and a control group (n = 53). Sick leave attributable to back pain was determined in the intervention period of 1 1/2 years and a comparable 1 1/2-year period prior to the study. In the exercise group, the number of episodes of back pain and the number of sick-leave days attributable to back pain in the intervention period decreased by over 50%. Absenteeism attributable to back pain increased in the control group. The decrease in sick leave in the exercise group was not accompanied by any change in cardiovascular fitness. Suggestions for establishing exercise programs are given.", "There are few data on the relative effectiveness and costs of treatments for low back pain. We randomly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy, chiropractic manipulation, or a minimal intervention (provision of an educational booklet). Patients with sciatica were excluded. Physical therapy or chiropractic manipulation was provided for one month (the number of visits was determined by the practitioner but was limited to a maximum of nine); patients were followed for a total of two years. The bothersomeness of symptoms was measured on an 11-point scale, and the level of dysfunction was measured on the 24-point Roland Disability Scale.\n After adjustment for base-line differences, the chiropractic group had less severe symptoms than the booklet group at four weeks (P=0.02), and there was a trend toward less severe symptoms in the physical therapy group (P=0.06). However, these differences were small and not significant after transformations of the data to adjust for their non-normal distribution. Differences in the extent of dysfunction among the groups were small and approached significance only at one year, with greater dysfunction in the booklet group than in the other two groups (P=0.05). For all outcomes, there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain. About 75 percent of the subjects in the therapy groups rated their care as very good or excellent, as compared with about 30 percent of the subjects in the booklet group (P<0.001). Over a two-year period, the mean costs of care were $437 for the physical-therapy group, $429 for the chiropractic group, and $153 for the booklet group.\n For patients with low back pain, the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs, and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet. Whether the limited benefits of these treatments are worth the additional costs is open to question.", "The purpose of this study was to compare the effect of the McKenzie method of treatment with patient education in \"mini back school\" in patients with acute low-back pain. The study included 100 patients, 23 women and 77 men with the average age 34.4 +/- 9.7 (range 18-61) years. The study included only those who were employed. The patients were randomly allocated to two groups, one group receiving treatment according to the McKenzie technique and the other group receiving education in a \"mini back school.\" Assessments were made after 3 weeks by an independent observer and after 52 weeks they were seen by one of the authors. Patients were assessed on seven variables: return to work, sick-leave during the initial episode, sick-leave during recurrences, recurrences of pain during the year of observation, patients' ability to self-help, pain and movement. Although the effect of attention placebo cannot be ruled out, the results demonstrated that the McKenzie method of treatment for patients with acute low-back pain was superior for five out of seven variables studied. The only variables that did not show any statistically significant differences were sick-leave during recurring episodes of pain and patients' ability to self-help.", "To assess the efficacy of exercise therapy for acute low back pain, a randomized, placebo-controlled trial was performed in 40 Dutch general practices. Patients received either exercise instruction with advice for daily life by a physiotherapist; placebo ultrasound therapy by a physiotherapist; or usual care by the general practitioner. All patients received analgesic agents and information on low back pain before randomization. Four hundred seventy-three patients were included. No differences in number of recurrences, functional health status, or medical care usage could be found among the three groups. In the exercise group, duration of recurrences was shorter and patients were less tired during the first 3 months than in the usual care group, but no differences were found between the exercise and placebo groups. It was concluded that exercise therapy for patients with acute low back pain has no advantage over usual care from the general practitioner.", "The study was carried out as an open, randomized, multicenter, parallel-group study with an observation period of 12 months. Four norwegian physiotherapy institutes took part. Patients were subsequently followed for 12 months of home exercise on their own, without for 12 months of home exercise on their own, without the supervision of a physiotherapist.\n 1) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1-year training program under the supervision of a physiotherapist. 2) To investigate the effect supervision by, and motivation from, physiotherapists has on training compliance and efficacy.\n After ordinary physiotherapy treatment for low back problems, patients were randomly allocated either to a conventional training program designed by physiotherapists or to a training program using a new Norwegian-developed training apparatus called the TerapiMaster. The study included 153 patients with low back problems, all of whom had been referred to physiotherapy by their general practitioners. One hundred twenty-six patients were followed for an additional 12 months when performing home exercise programs on their own.\n Monitoring patient satisfaction with the training program, compliance with the program, and absenteeism from work during the training period.\n Patient satisfaction with both training programs was high, with about 83% of participating patients completing the study in accordance with the protocol. Mean absenteeism (SD) during the preceding year totaled 82.5 days (19.8) in the conventional training group and 61.6 days (14.7) in the TerapiMaster group. Significant reductions to 17.2 days (6.0) and 16.4 days (5.3) in the two groups, respectively, were recorded during the training period, corresponding to a 75% to 80% reduction compared with the preceding 1-year period. Mean absenteeism showed a further significant decline during the 12-month period without supervised training. The average values were 9.9 days (3.2) for conventional training and 9.3 days (3.1) for the TerapiMaster, respectively.\n Both exercise programs reduced absenteeism significantly (75-80%). No difference in the effects of the two different programs was discernible. Regular follow-up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems. This thesis was corroborated by the 12-month study of unsupervised exercise.", "A prospective, randomized, controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group.\n To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working.\n One episode of low back pain increases the risk of further episodes of the condition. The Mensendieck approach combines education and exercise. This approach has been used for many years in Scandinavia and the Netherlands. However, the effects on low back pain have not been evaluated previously in a randomized, controlled trial.\n A total of 77 men and women, mean age 39.6 years (range, 21.2-49.8 years), who had finished treatment for a low back pain episode, were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years. The patients were assigned at random to either the Mensendieck program or a control group. The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks. At 5- and 12-month follow-up examinations, the patients were assessed for recurrence of low back pain, days of sick leave, low back pain, and functional scores.\n After 12 months, there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group (P < 0.05). There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group, but no significant differences between the groups. There was reduction in pain and improvement in function in both groups, with no significant differences between the groups.\n A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition. However, there were no differences between the groups with regard to days of sick leave, low back pain, and function.", "A randomized clinical trial.\n To evaluate long-term clinical and economical effects of a light mobilization program on the duration of sick leave for patients with subacute low back pain.\n Twelve-month follow-up results from a previous study showed that early intervention with examination at a spine clinic, giving the patients information, reassurance, and encouragement to engage in physical activity as normal as possible had significant effect in reducing sick leave. At 12-month follow-up, 68.4% in the intervention group were off sick leave, as compared with 56.4% in the control group. Patients in this study were followed-up for a period of 3 years to investigate possible long-term effects.\n Four hundred fifty-seven patients placed on a sick list for 8 to 12 weeks for low back pain were randomized into two groups: an intervention group (n = 237) and a control group (n = 220). The intervention group was examined at a spine clinic and given information and advice to stay active. The control group was not examined at the clinic but was treated within the primary health care.\n Over the 3 years of observation, the intervention group had significantly fewer days of sickness compensation (average 125.7 d/person) than the control group (169.6 d/person). This difference is mainly caused by a more rapid return to work during the first year. There was no significant difference for the second or third year. In particular, there is no increased risk for reoccurrence of illness from early return to work. At 6-month follow-up, patients in the intervention group were less likely to use bed rest and more likely to use stretching and walking to cope with their back pain compared with the control group. This effect diminished. At 12-month follow-up, the only significant difference between the groups was in the use of stretching. Economic returns of the intervention were calculated in terms of increases in the net present value of production for the society because of the reduction in number of days on sick leave. Net benefits accumulated over 3 years of treating the 237 patients in the intervention group amount to approximately 2,822 dollars per person.\n For patients with subacute low back pain, a brief and simple early intervention with examination, information, reassurance, and encouragement to engage in physical activity as normal as possible had economic gains for the society. The effect occurred during the first year after intervention. There were no significant long-term effects of the intervention. The initial gain obtained during the first year does not lead to any increased costs or increased risks for reoccurrence of illness over the next 2 years." ]

[ "144507", "6342625" ]

[ "Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis.", "Low-dose D-penicillamine therapy in rheumatoid arthritis. A controlled, double-blind clinical trial." ]

[ "In order to evaluate clinical efficacy of D-penicillamine (DP) a double-blind study was conducted by the Metalcaptase Research Group consisting of forty-one rheumatological centers in Japan. A total of 179 patients with rheumatoid arthritis (RA) was divided into two groups; one treated with 5 mg (control group) and the other with 100 mg (drug group) of DP in capsule form. The trial lasted 24 weeks. Global judgment by physicians revealed that improvement was found in 27% in the controls and 65% in the drug group. Adverse reactions occurred in 34% of the controls and 49% of the drug group. Skin rashes, taste disturbances, gastrointestinal upset and proteinuria were frequent in the drug group, but severe or fatal reactions could not be seen in this trial.", "Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity." ]

[ "16097980", "4596724", "11166746", "11523256", "12113971", "10426640", "9926882", "10688504", "9926890", "12407329", "12421172", "10399256", "9808382" ]

[ "The modified Misgav-Ladach versus the Pfannenstiel-Kerr technique for cesarean section: a randomized trial.", "Extraperitoneal lower segment caesarean section for infected cases. A reappraisal.", "Can Joel-Cohen incision and single layer reconstruction reduce cesarean section morbidity?", "Study on modification of the Misgav Ladach method for cesarean section.", "Comparison of two transverse abdominal incisions for cesarean delivery.", "Modified Joel-Cohen technique for caesarean delivery.", "A randomized clinical trial of two surgical techniques for cesarean section.", "Introduction of the Misgav Ladach caesarean section at an African tertiary centre: a randomised controlled trial.", "The Misgav Ladach method for cesarean section compared to the Pfannenstiel method.", "[Comparison of two cesarean techniques: classic versus Misgav Ladach cesarean].", "Joel-Cohen or Pfannenstiel incision at cesarean delivery: does it make a difference?", "[In Process Citation]", "Short-term outcome of newborn infants born by a modified procedure of cesarean section. A prospective randomized study." ]

[ "Modifications to the classic cesarean section technique described by Pfannenstiel and Kerr have been proposed in the last few years. The objective of this trial was to compare intraoperative and short-term postoperative outcomes between the Pfannenstiel-Kerr and the modified Misgav-Ladach (MML) techniques for cesarean section.\n This prospective randomized trial involved 162 patients undergoing transverse lower uterine segment cesarean section. Patients were allocated to one of the two arms: 88 to the MML technique and 74 to the Pfannenstiel-Kerr technique. Main outcome measures were defined as the duration of surgery, analgesic requirements, and bowel restitution by the second postoperative day. Additional outcomes evaluated were febrile morbidity, postoperative antibiotic use, postpartum endometritis, and wound complications. Student's t, Mann-Whitney, and Chi-square tests were used for statistical analysis of the results, and a p < 0.05 was considered as the probability level reflecting significant differences.\n No differences between groups were noted in the incidence of analgesic requirements, bowel restitution by the second postoperative day, febrile morbidity, antibiotic requirements, endometritis, or wound complications. The MML technique took on average 12 min less to complete (p = 0.001).\n The MML technique is faster to perform and similar in terms of febrile morbidity, time to bowel restitution, or need for postoperative medications. It is likely to be more cost-effective.", "nan", "To compare an innovative cesarean section based on Joel-Cohen incision with the traditional Pfannenstiel technique in terms of operative data and post-operative recovery.\n Out of 158 randomized patients, 83 patients underwent the innovative cesarean section (Joel-Cohen incision, one-layer locked uterine suture, no peritoneization) and 75 the traditional operative approach (Pfannenstiel incision, double layer closure of the uterus, visceral and parietal peritoneization). Operative data and post-operative morbidity were compared; sample size was calculated to detect a 13% difference in the occurrence of post-operative fever with a statistical power of 80%.\n Post-operative fever was not different in the two groups. Total operating time was shorter with the innovative technique: 31.6 +/-1.38 min vs. 44.4+/-1.44 (P=0.0001) and fewer sutures were used: 3.6+/-0.13 vs. 6+/-0.13 (P=0.001). Patients operated by the new technique began moving sooner and intestinal function restarted earlier.\n The proposed technique made for shorter operating times and faster recovery but no decrease in puerperal morbidity.", "172 cases of pregnant women scheduled for delivery by cesarean section were randomly assigned to 59 cases in modification group with modified Misgav Ladach technique, 57 cases in Misgav Ladach group with Misgav Ladach technique and 56 cases in Pfannenstiel group with Pfannenstiel technique from May to Dec. 1999. The modified points included: transversely incising the fascia 2 to 3 cm, then dividing it bluntly; without opening and dissociating the visceral peritoneum; two layers suturing of low transverse uterine incision; closing the skin by continuous suturing. Results showed the average delivery time in the modification group was (3.6 +/- 2.6) min and (5.7 +/- 2.9) min in the Misgav Ladach group (P < 0.05). Median operating time was (28.3 +/- 5.4) min in modification group compared with (27.5 +/- 6.5) min in the Misgav Ladach group (P > 0.05). Average blood loss was (128 +/- 35) ml in modification group compared with (212 +/- 147) ml in the Pfannenstiel group (P < 0.05). It was concluded that the modified Misgav Ladach technique not only preserved all advantages of Misgav Ladach method, but also had additional advantages, such as faster in delivering the fetus, less damage, easier mastering for obstetricians.", "nan", "To investigate whether a series of changes in the current caesarean section operative routine, based on new knowledge, would be beneficial.\n A prospective controlled trial.\n Labour ward with approximately 3000 deliveries annually in a suburban area of Gothenburg, Sweden.\n Seventy-two pregnant women scheduled for delivery by caesarean section were randomised to either modified Joel-Cohen technique (n = 36) or Pfannenstiel technique (n = 36).\n Blood loss during surgery and operating time.\n The median estimated intra-operative blood loss was 250 mL in the modified Joel-Cohen group and 400 mL in the Pfannenstiel group (P = 0.026). The proportion of women with > or = 300 mL was 16/36 in the modified Joel-Cohen group vs 28/36 in the Pfannenstiel group (OR 0.229, 95% CI 0.082-0.637). Median operating time was 20 min in the modified Joel-Cohen group compared with 28 min in the Pfannenstiel group (P < 0.001). The proportion of women with > or = 25 min was 1/36 in the modified Joel-Cohen group vs 33/36 in the Pfannenstiel group (OR 0.003, 95% CI 0.000-0.026).\n We conclude that the modified Joel-Cohen technique of caesarean delivery reduced intraoperative blood loss and operating time compared with the Pfannenstiel technique.", "The Joel-Cohen incision followed by nonclosure of pelvic and parietal peritoneum has been advocated as an alternative method to the Pfannenstiel incision with peritonealization at cesarean section. A randomized trial was designed to compare intra- and postoperative morbidity between the two techniques. Women to undergo a cesarean section were randomly allocated to have either the Joel-Cohen incision with the parietal and pelvic peritoneum left open (group 1) or to have the Pfannenstiel incision with both peritoneal layers sutured (group 2). The myometrium was closed with 1-0 polyglactin 910 suture using a continuous single-layer nonlocking technique. Patients in group 2 had the peritoneum approximated with 2-0 polyglactin 910 suture. The fascia was sutured with continuous 1-0 polyglactin 910 suture in all cases. Opening time was defined as the interval from skin incision to the opening of the uterine cavity. Febrile morbidity was defined as a temperature > or =38 degrees C on two occasions 4 hours (hr) apart excluding the first postoperative day. Endometritis was defined as postpartum temperature > or =38 degrees C on two occasions 4 hr apart, with uterine tenderness and/or foul-smelling lochia. One hundred forty-nine and 150 patients were allocated to group 1 and to group 2, respectively. A shorter median (range) opening time [4 min (2-21) vs. 6 min (2-19), respectively, p < 0.01] and a shorter median (range) operative time [30 min (10-65) vs. 40 min (20-110), respectively, p < 0.01] were observed in group 1. No difference was found in terms of intraoperative complications, proportion of patients who required transfusion, endometritis, sepsis, febrile morbidity, and urinary tract infections. A higher rate of wound infections was found in group 2 than in group 1 [14 of 150 (9.3%) vs. 2 of 149 (1.3%), respectively, p < 0.01]. The Joel-Cohen incision without peritonealization resulted in a shorter opening and total operative time than the Pfannenstiel laparotomy with peritonealization. This was accomplished with a reduction of wound infections.", "To determine whether the Misgav Ladach caesarean section technique can offer benefits compared with conventional caesarean section technique in the prevailing conditions of a busy African tertiary centre.\n A randomised controlled trial.\n A tertiary African obstetric unit with 18,000 deliveries annually.\n Three hundred and thirty-nine women undergoing caesarean section.\n Eight residents and registrars were instructed in the Misgav Ladach technique for caesarean section during one week, after which the study commenced. The course participants instructed their colleagues; in total, 16 doctors participated. Women requiring caesarean section were randomised to Misgav Ladach or to the conventional lower midline incision procedure, excluding those with a previous scar.\n During 11 weeks 339 randomised procedures (328 of which were emergency procedures) were carried out. Mean operating time was 25 x 3 minutes for Misgav Ladach and 32 x 6 minutes for the lower midline incision procedure (95% CI -8 x 3; -6 x 3). Mean blood loss was 354 mL and 447 mL (-133; -53), and the number of sutures 3 x 1 and 6 x 1 (-3 x 1; -2 x 9), respectively. No significant difference was found in Apgar scores. Mobilisation was earlier with the Misgav Ladach procedure. No difference was found in overall post-operative infection rates i.e. wound infection or febrile illness, but the combination of wound infection and fever was more common in the Misgav Ladach group.\n The Misgav Ladach caesarean section confers benefits such as reduced blood loss, conservation of time and suture material, and rapid mobilisation, but more studies are needed to explore modifications aimed at reducing post-operative infections in settings with limited resources.", "The aim of the study was to evaluate the outcome of two different methods of cesarean section (CS).\n The study was designed as a prospective, randomized, controlled trial.\n All CS were performed at the University Hospital in Uppsala, Sweden.\n Fifty women admitted to hospital for a first elective CS were consecutively included in the study. They were randomly allocated to two groups.\n One group was operated on by the Misgav Ladach method for CS and the other group by the Pfannenstiel method. All operations were performed by the same surgeon.\n Duration of operation, amount of bleeding, analgesics required, scar appearance and length of hospitalization.\n Operating time was significantly different between the two methods, with an average of 12.5 minutes with the Misgav Ladach method and 26 minutes with the Pfannenstiel method (p<0.001). The amount of blood loss differed significantly, with 448 ml and 608 ml respectively (p=0.017). Significantly less analgesic injections and tablets (p=0.004) were needed after the Misgav Ladach method.\n The Misgav Ladach method of CS has advantages over the Pfannenstiel method by being significantly quicker to perform, with a reduced amount of bleeding and diminished postoperative pain. The women were satisfied with the appearance of their scars. In this study no negative effects of the new operation technique were discovered.", "The aim of the study was to compare two cesarean section techniques Methodology. A prospective study was conducted UB 400 cesareans performed at the Gynecological and Obstetric Clinic of the Dakar Teaching Hospital between March 2000 and August 2000. Two hundred patients underwent the classical procedure (CL group) and the other 200 the Misgav Ladach procedure (ML group). Per- and post-operative data were compared between the two groups with Student's test and the Chi(2) test. A p-value less than 0.05 was considered statistically significant.\n The two groups were similar for socio-demographic and clinical data. The delay between the skin incision and infant delivery was significantly shorter in the ML group (5 minutes 26 seconds versus 6 minutes 20 seconds). The same trend was found for the length of operation (36 minutes 36 seconds versus 54 minutes 38 seconds). Fewer sutures were used in the ML group (2.92 versus 4.14). There is no significant difference for dose of analgesia, post-operative complications and hospital discharge. Cost analysis demonstrated that the Misgav Ladach procedure was 10000 FCFA (15 euros) less costly.\n Misgav Ladach method is simple, rapid, cost-effective cesarean procedure which appears to be an attractive alternative to traditional cesarean section.", "To evaluate whether the technique to open the abdomen might influence the operative time and the maternal and neonatal outcome.\n All consecutive women who underwent a cesarean section at a gestational age greater than or equal to 32 weeks were randomly allocated to have either the Joel-Cohen or the Pfannenstiel incision. Exclusion criteria were two or more previous cesarean sections and previous longitudinal abdominal incision. During the study period 366 patients underwent a cesarean delivery. Of these patients, 56 did not meet the inclusion criteria. The remaining patients were allocated to the Joel-Cohen (n = 152) group and to the Pfannenstiel (n = 158) group. Extraction time was defined as the time interval from skin incision to the clamping of the umbilical cord.\n The total operative time was similar in both groups [Joel-Cohen 32 min (12-60) vs. Pfannenstiel 33 min (18-70)]. The extraction time was shorter in the Joel-Cohen group than in the Pfannenstiel group [190 s (60-600) vs. 240 s (50-600), p = 0.05]. This remained statistically significant after adjustment for confounding variables (Hazard = 1.26, p = 0.05). No difference was found between groups in terms of intraoperative and postoperative complications. No difference was found in the neonatal neurodevelopmental assessment at 6 months of age in relation to the abdominal incision performed.\n The Joel-Cohen method of opening the abdomen at cesarean delivery is faster then the Pfannenstiel technique at delivering the fetus. However, considering the absence of benefits to the mother and the fetus there is no clear indication for performing a Joel-Cohen incision.", "This paper was intended to settle the question whether the so-called gentle sectio caesarea with a high skin incision as described by Cohen in 1972 [2] could be applied in combination with a sectio on the level of the classic Pfannenstiel's incision which would be more satisfying cosmetically. Furthermore a comparison was to be drawn between the postoperative condition of those patients on whom this surgical method had been performed and the condition following a classic Pfannenstiel's incision. Between January 1997 and July 1997 we compared the classic method of Pfannenstiel's incision with the variant of Cohen's method as described above in a prospective randomised study. On applying this surgical technique, the abdomen was opened according to Cohen's method using a surgical knife but for the skin, and the tissue layers underneath were opened blunt with two fingers. Following the extraction of the child only three sutures were made: Uterus, fascia and skin. Redon drainages were not inserted. We were able to show that this method of applying mainly blunt \"incision\" to sectio caesarea the tissue is at least equal to the sharp opening of the abdominal cavity. In some respects, such as the early postoperative mobilisation, it is, in fact, superior, because the blunt opening causes less bleeding and the reduction to three sutures only, deliberately leaving the two peritoneal membranes open, as well as leaving away the redon drainages, considerably increases the patients' postoperative well-being. It is for these reasons that we call for this method to become part of the routine procedures in caesarean sectio.", "nan" ]

[ "1455306", "16132406", "16284796", "12691930", "1733360", "1677616", "11683740", "9824933", "18299182", "7742052", "8156354", "1373231", "10973392", "15006886", "1351276", "21694864", "7552016", "7809832" ]

[ "A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas.", "Prospectively randomized trial using perioperative low-dose octreotide to prevent organ-related and general complications after pancreatic surgery and pancreatico-jejunostomy.", "Effects of somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma motilin.", "The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial.", "Role of octreotide in the prevention of postoperative complications following pancreatic resection.", "[Effect of somatostatin on basal and stimulated exocrine pancreatic secretion after partial duodenopancreatectomy. A clinical experimental study].", "Randomized controlled multicentre trial of somatostatin infusion after pancreaticoduodenectomy.", "[Prospective and randomized study on the usefulness of octreotide in the prevention of complications after cephalic duodeno-pancreatectomy].", "Prophylactic octreotide and delayed gastric emptying after pancreaticoduodenectomy: results of a prospective randomized double-blinded placebo-controlled trial.", "[Somatostatin prophylaxis following cephalic duodenopancreatectomy].", "Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. Italian Study Group.", "[Somatostatin in the prevention of postoperative increase of pancreatic enzyme after pancreatic surgery].", "Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial.", "Octreotide in the prevention of intra-abdominal complications following elective pancreatic resection: a prospective, multicenter randomized controlled trial.", "[Somatostatin in duodenocephalopancreatectomy for neoplastic pathology].", "The role of somatostatin in 67 consecutive pancreatectomies: a randomized clinical trial.", "Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis.", "Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial." ]

[ "Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas.\n Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded.\n Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different.\n Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas.", "The aim of the present study was to evaluate the influence of low-dose perioperative octreotide on the prevention of complications (pancreatic fistula and general complications) in patients undergoing pancreatic surgery followed by pancreaticojejunostomy. A total of 105 patients were randomized to receive either octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no octreotide. The primary endpoints were the occurrence of a pancreatic fistula and or general complications, including extended length of hospital stay. There were 25 surgical draining procedures performed and 80 duodenopancreatectomies with or without preservation of the pylorus. In all, 25 (23.8%) of the patients were treated for chronic pancreatitis, 8 (7.6%) for benign tumoral disease, and 72 (68.6%) for carcinoma. All patients underwent pancreaticojejunostomy.", "Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue damage and pancreatic stump complications. Because our earlier clinical work saw a major increase in delayed gastric emptying (DGE) with somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy (PPPD), this small-group study was designed to confirm or disprove that observation. From August 1997 to December 2000, a total of 23 post-PPPD patients were randomized to receive somatostatin prophylaxis [somatostain (+)] (n = 11) or not [somatostatin] (-) (n = 12). The incidence of DGE, scintographic solid-phase emptying results on day 14 postoperatively, and sequential fasting plasma motilin levels were compared, as motilin levels are related to both gastric motility and somatostatin levels. The somatostatin(+) group exhibited greatly increased patient complaints of DGE: 9 of 11 (82%) versus 3 of 12 (25%) in the somatostatin(-) group. Radiologic scintography showed somatostatin prophylaxis prolonged the half-time (T(1/2)) of solid-phase emptying: 144.5 +/- 51.4 minutes for somatostatin(+) versus 89.0 +/- 59.9 minutes for somatostatin(-) (p < 0.001). Comparing pre-PPPD and post-PPPD plasma motilin levels prior to somatostatin infusion, motilin decreased 80% in reaction to the surgery. For somatostatin(-) patients, motilin levels oscillated, or \"rang,\" postoperatively, reaching a higher level on day 3, declined to a new record minimum on day 7, and by day 21 were 50% of the original and the slope of the recovery curve was increasing well. In somatostatin(+) patients the same ringing pattern was observed but decreased with motilin levels 30% to 70% lower than in the somatostatin(-) patients. By day 21 somatostatin(+) motilin levels were recovering but still only 20% original levels, and the slope of the recovery curve was not optimistic. On postoperative day 14 the plasma motilin levels (below approximately 6 bg/ml) correlated strongly with DGE for both groups. Despite the small sample size, the results indicated that (1) somatostatin prophylaxis significantly decreases fasting plasma motilin; (2) somatostatin prophylaxis produces lingering suppression of plasma motilin; (3) PPPD surgery itself significantly reduces fasting motilin levels with recovery to 50% normal at day 21; (4) the mechanism of somatostatin-induced DGE seems related to reduced fasting plasma motilin levels.", "Pancreatectomy can be complicated by pancreatic anastomotic leakage, causing major morbidity.\n Our aim was to determine if vapreotide, a potent long-acting somatostatin analogue, would decrease pancreas-related complications. This prospective, multicenter, randomized, double-blind, placebo-controlled trial involved 275 patients without preexisting chronic pancreatitis undergoing elective proximal, central, or distal pancreatectomy. Complications were defined by objective criteria before beginning the study.\n One hundred thirty-five patients received vapreotide; 140 patients received placebo. There were no statistically significant differences between vapreotide- and placebo-treated patients in either pancreas-related complications (30.4% versus 26.4%, respectively) or in other complications not directly related to the pancreas (40% versus 42%, respectively).\n The potent somatostatin analogue vapreotide does not appear to decrease postoperative complications after major pancreatectomy in patients without chronic pancreatitis.", "Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.", "In a prospective trial 30 patients underwent pancreaticoduodenectomy (Whipple operation) for cancer. They were randomly assigned to receive Somatostatin (SST) (n = 15) or not (n = 15). SST was started at laparotomy with 250 micrograms/h and given over a period of 5 days. A small catheter, which was placed into the duct of the pancreatic remnant, gave access to the pancreatic juice. Volume, amylase, lipase and protein as well as bicarbonate outputs were analyzed. As regards endocrine function, insulin and glucagon plasma levels were measured. The nitrogen balance was calculated. A stimulation test was done on the fifth postoperative day. Six patients (3/3) were assessed as drop-outs. A significant reduction was found for volume, amylase, lipase, protein and bicarbonate with SST, this effect lasting for two days. Lipase however was reduced significantly for 5 days. Pancreatic exocrine function was reduced as well after stimulation, if SST was given. Insulin and glucagon were inhibited with SST, the latter more effectively. We found a positive nitrogen-balance as early as on the second postoperative day in the SST-group, whereas without SST this did not occur before the fourth postoperative day. This findings were significant on the third and fourth postoperative day. The inhibitoric effects of SST, which are demonstrated by our laboratory investigations, conform very well with a more favorable clinical course and a reduction of perioperative morbidity and mortality.", "It remains debatable whether somatostatin can prevent pancreatic fistula and other pancreatic stump-related complications following pancreaticoduodenectomy. This study assessed the effects of somatostatin-14 (S-14) on pancreatic remnant exocrine secretion.\n This was a double-blind, randomized, placebo-controlled trial in patients undergoing pancreaticoduodenectomy for malignancy. Patients received a continuous infusion of S-14 (n = 38) or placebo (n = 37) for 7 days. Pancreatic juice and peripancreatic drainage fluid was collected and measured, and pancreatic enzymes were monitored daily. Postoperative complications were recorded.\n S-14 infusion was associated with a decrease in median daily pancreatic juice and pancreatic amylase output. Amylase concentration and output in the peripancreatic drain fluid were significantly lower after S-14 infusion than in the control group (both P < 0.05). The incidence of clinical pancreatic fistula (two of 38 versus eight of 37; P < 0.05) and total pancreatic stump-related complications (five of 38 versus 12 of 37; P < 0.05) was lower in patients treated with S-14. Duration of hospital stay was shorter after S-14 (18 versus 26 days; P = 0.01).\n Although the effect of S-14 on exocrine secretion remains difficult to demonstrate, it did reduce pancreatic juice leakage from the pancreatic remnant.", "This study seeks to evaluate the role of the somatostatin analogue Octreotide as postoperative prophylaxis in the prevention of pancreatic fistula following Pancreaticoduodenectomy (PD).\n A prospective and randomized study has been completed in 34 patients undergoing PD. Sixteen patients were randomly assigned to receive Octreotide 0.1 cc (100 mcg) three times daily subcutaneously during the first seven days of the post-operative period and the remaining 18 constituted the control group. All patients were fed parenterally until normal oral feeding was restored (mean 8 days). Fisher's exact test was used to compare complications in both groups. Pancreatic fistula was defined as the persistence of an amylase-rich discharge at least 50 ml daily during a minimum period of two weeks.\n The mortality rate was 3% and the morbidity 26%. No significant differences were observed regarding the total number of complications. The appearance of pancreatic fistula was considerably smaller (p = 0.03) in the Octreotide group than in control group. Postoperative hospital stay and the number of subsequent surgical interventions were significantly higher (p < 0.05) in the control group.\n Octreotide prevents the occurrence of pancreatic fistula after PD when it is administered prophylactically during the immediate postoperative period.", "To evaluate the impact of prophylactic octreotide on gastric emptying in patients undergoing pancreaticoduodenectomy. Postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) are common complications after pancreaticoduodenectomy. Whereas several prospective randomized trials propose the prophylactic use of octreotide to prevent pancreatic fistula formation, somatostatin has, however, been associated with delayed gastric emptying after partial duodenopancreatectomy.\n In this prospective, randomized, double-blinded, placebo-controlled trial we analyzed the influence of prophylactic octreotide on delayed gastric empting after pancreaticoduodenectomy. Patients were randomized to the placebo group (n=32) and the octreotide group (n=35). Primary endpoint was the incidence of delayed gastric emptying, secondary endpoints included perioperative morbidity other than DGE. DGE was measured by clinical signs, gastric scintigraphy and the hydrogen breath test. Risk factors for DGE other than octreotide were analyzed by univariate and multivariate analyses.\n DGE measured by clinical signs was similar between both groups studied ( approximately 20% of the patients). Gastric scintigraphy (T(1/2)) was 76.3+/-15.2 min in the octreotide group and 86.7+/-18.0 min in controls at day 7, respectively. The H(2) breath test was 65.0+/-6.5 min in octreotide treatment group and 67.0+/-5.7 min in controls at day 8. POPF grade C occurred in approximately 3% of the patients, although prophylactic treatment of octreotide did not reduce the incidence of POPF. Multivariate analysis showed that postoperative intraabdominal bleeding and infection were independent risk factors for DGE. Furthermore preoperative biliary stenting reduced postoperative DGE after partial duodenopancreatectomy.\n Prophylactic octreotide has no influence on gastric emptying and does not decrease the incidence of postoperative pancreatic fistula after pancreaticoduodenectomy.", "This study was aimed at assessing the value of prophylactic somatostatin after cephalic duodenopancreatectomy. A randomized prospective study was undertaken using two groups of patients, one with prophylactic somatostatin (4.5 mg daily in continuous perfusion for 7 days postoperatively), known as group I, and group II, which did not receive somatostatin. During a five-year period, from April 1989 to April 1994, we performed 35 duodenopancreatectomies, of which 21 belonged to group I and 14 to group II. We found a lower incidence of pancreatic anastomosis fistulae in group I (9.5% vs 35.7%; p < 0.05). We did not find any correlation between prophylaxis with somatostatin and the appearance of other complications or postoperative mortality. The mean time of fistula closure in group I was 5 days while that of group II was 19.2 days. In conclusion, the administration of prophylactic somatostatin after cephalic duodenopancreatectomy reduces the incidence and duration of pancreatic fistula.", "A placebo-controlled double-blind multicentre study, with randomization into parallel groups, was performed to determine whether perioperative subcutaneous administration of octreotide 0.1 mg every 8 h reduces the rate of complications specifically related to pancreatic surgery. In all, 252 patients were evaluated (153 men, 99 women; mean(s.e.m.) age 53.1(0.8) years) who had pancreatic or periampullary tumour or other duodenal disease (157 patients) or chronic pancreatitis (95) and were undergoing elective pancreatic resection (100 Whipple's procedure, 60 distal resection, 12 others), pancreaticojejunostomy (66) or enucleation of pancreatic lesions (14). The proportion of patients with complications was significantly lower in the group treated with octreotide than in the placebo group (15.6 versus 29.2 per cent, P = 0.01). Octreotide thus appears to reduce substantially the risk of complications related to elective pancreatic surgery. Moreover, treatment acceptability was high.", "The prophylactic effect of perioperative use of somatostatin on postoperative increase of pancreatic digestive enzymes was investigated in this double blind, randomized study. Thirty three patients undergoing pancreatic surgery because of chronic pancreatitis were divided randomly into two groups. Fifteen patients received somatostatin- (dose 125 micrograms/hour), 18 placebo-infusion, pre- and postoperatively for a total time of 48 hours. The level of serum amylase, lipase, gammaGT, calcium, creatinine and blood glucose was determined every 12 hours. In the placebo group the serum lipase and amylase increased significantly (p less than 0.001), while the calcium decreased. In the somatostatin treated patients only the lipase level increased significantly (p less than 0.01), while the amylase and calcium showed no significant changes compared to their initial values. The postoperative increase in serum enzyme levels is interpreted as being an indicator of pancreatic injury. These results suggest that the perioperative use of somatostatin has beneficial effect for the prevention of pancreatic enzymes increases, associated with pancreatic surgery or its complications in patients with chronic pancreatitis.", "To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy.\n Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652.\n Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay.\n Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups.\n These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings.", "Prophylactic administration of octreotide acetate decreases the rate of postoperative intra-abdominal complications (IACs) after elective pancreatic resection.\n Single-blind, controlled, randomized trial.\n Multicenter (N = 20) trial in France.\n Of 230 randomized patients undergoing pancreatoduodenectomy and pancreatic enteric anastomosis or distal pancreatectomy for either malignant or benign tumor or chronic pancreatitis, 122 were allotted intraoperatively to receive octreotide; 108 served as controls.\n All 230 patients were analyzed. Both groups were comparable except that significantly more patients in the octreotide group had biological glue injected into the main pancreatic duct alone (P<.001) or reinforcing the pancreatic enteric anastomosis (68% [83/122] vs 39% [42/108]; P =.002). Fewer patients (P =.08) in the octreotide group sustained 1 or more IACs (22% vs 32%). In subgroup analysis, octreotide significantly reduced the rate of patients sustaining 1 or more IACs when the main pancreatic duct diameter was less than 3 mm (P<.02), when pancreatojejunostomy was performed (P<.02), or both (P<.02). No significant differences were found regarding IAC severity. Twenty-three patients (10%) died postoperatively, 16 (70% of deaths) of whom had 1 or more IACs. The only independent risk factor for IACs found on multivariate analysis was pancreatoduodenectomy compared with distal pancreatectomy (P<.01) (odds ratio, 3.54 [95% confidence interval, 1.44-8.65]).\n Our results suggest that octreotide is not necessary for all patients undergoing pancreatic resection; it could be useful when the main pancreatic duct is less than 3 mm in diameter and when pancreatoduodenectomy is completed by pancreatojejunostomy.", "nan", "Somatostatin has been found to be effective in the prevention of postoperative complications in pancreatic surgery. It can inhibit the pancreatic secretions that, quite often, are responsible for complications during the postoperative period.\n We randomized 67 patients in 2 groups. In the study group (n = 35), somatostatin was administered 30 minutes prior to surgery as well as intraoperatively and postoperatively. No medication was given to the control group (n = 32). Biopsies were taken and processed for electron microscopy and ultrastructural morphometric analysis.\n Administration of somatostatin reduced the exocrine granule number, and the patients suffered from fewer postoperative complications.\n Somatostatin reduces granule number and size of pancreatic cells, which can partially explain the prophylactic effect of the drug on early complications of pancreatic surgery, and which is confirmed by the clinical findings.", "A randomized double-blind placebo-controlled multicentre trial was carried out in 247 patients undergoing major elective surgery for chronic pancreatitis to clarify whether the perioperative application of octreotide prevents postoperative complications. Eleven complications were defined, including death, anastomotic leakage, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency and postoperative pancreatitis. A total of 124 patients underwent pancreatic head resection, 55 left resection, 61 pancreaticojejunostomy and seven had other procedures. The overall mortality rate was 1.2 per cent (octreotide group 1.6 per cent, placebo group 0.8 per cent [corrected] (P not significant)). The postoperative complication rate in the octreotide group was 16.4 per cent (20 of 122 patients) and in the placebo group 29.6 per cent (37 of 125) (P < 0.007). The perioperative application of octreotide substantially reduces the risk of postoperative complications in patients undergoing major pancreatic surgery for chronic pancreatitis.", "A prospective, randomized controlled clinical trial was conducted in 33 Italian surgical departments with the aim of evaluating the efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections.\n Between July 1990 and May 1992, 278 patients were enrolled in the study. Fifty-four dropped out because of unresectable disease and six were excluded because of protocol violation; the remaining 218 were randomly assigned to the octreotide group (n = 111) or to the placebo group (n = 107). There were 131 men and 87 women with a mean age of 58.2 +/- 11.7 yrs. Pancreaticoduodenectomy was the most common operation performed (n = 143), sixty-four percent of patients had a pancreatic or periampullary cancer; chronic pancreatitis accounted for 8.2% of cases.\n Mortality rate was 6.9%. A pancreatic fistula occurred in 31 patients (14.2%), 9% in the octreotide group and 19.6% in the placebo group (p < 0.05). Morbidity rate was significantly lower in the octreotide (21.6%) than in the placebo group (36.4%) (p < 0.05). When specific pancreatic complications were grouped together and evaluated, they occurred less frequently in the treated (15.3%) than in the placebo group (29.9%) (p < 0.05).\n Octreotide was able to reduce significantly the incidence of pancreatic fistula after elective pancreatic resections." ]

[ "7999849", "8629630", "9152821", "9159313", "1626207", "1777589", "2085577", "1867179", "8076441", "8959632", "1855327", "11054359", "9027792", "1361797", "6106868", "8840945" ]

[ "The treatment of Staphylococcus aureus nasal carriage in pediatric peritoneal dialysis patients.", "A randomized trial of Staphylococcus aureus prophylaxis in peritoneal dialysis patients: mupirocin calcium ointment 2% applied to the exit site versus cyclic oral rifampin.", "The use of povidone iodine in exit site care for patients undergoing continuous peritoneal dialysis (CAPD).", "The efficacy of exit site povidone-iodine ointment in the prevention of early peritoneal dialysis-related infections.", "Prophylactic antibiotics in the insertion of Tenckhoff catheters.", "Preventing Staphylococcus aureus infection during chronic peritoneal dialysis.", "Exit-site care and exit-site infection in continuous ambulatory peritoneal dialysis (CAPD): results of a randomized multicenter trial.", "Randomized controlled trial of prophylactic rifampin for peritoneal dialysis-related infections.", "Effect of sodium fusidate and ofloxacin on Staphylococcus aureus colonization and infection in patients on continuous ambulatory peritoneal dialysis.", "Nasal mupirocin prevents Staphylococcus aureus exit-site infection during peritoneal dialysis. Mupirocin Study Group.", "Vaccination for prevention of CAPD associated staphylococcal infection: results of a prospective multicentre clinical trial.", "Role of preoperative antibiotic prophylaxis in preventing postoperative peritonitis in newly placed peritoneal dialysis catheters.", "One-dose cefuroxime i.v. and i.p. reduces microbial growth in PD patients after catheter insertion.", "Treatment of Staphylococcus aureus nasal carriers in CAPD with mupirocin.", "Prophylactic cephalexin ineffective in chronic ambulatory peritoneal dialysis.", "A prospective randomized control study of oral nystatin prophylaxis for Candida peritonitis complicating continuous ambulatory peritoneal dialysis." ]

[ "This study evaluates the dialysis-related infection rate in children receiving peritoneal dialysis with Staphylococcus aureus nasal carriage. Children with S. aureus nasal carriage were randomized to treatment with rifampin and bacitracin or no treatment. The children were observed for one month after randomization for evidence of a S. aureus dialysis-related infection. Individuals with nasal carriage had a higher incidence of S. aureus dialysis-related infection than those patients without carriage (p < 0.05). Those children treated for nasal carriage had a lower dialysis-related infection rate than those who were untreated (p < 0.05). We conclude that children receiving peritoneal dialysis with nasal carriage of S. aureus are at a greater risk of developing a S. aureus dialysis-related infection. The treatment of nasal carriage in this population decreased the risk of a S. aureus dialysis-related infection.", "The objective of this study was to compare prophylaxis for Staphylococcus aureus infections in peritoneal dialysis patients using 600 mg cyclic oral rifampin for 5 days every 3 months versus mupirocin calcium ointment 2% applied daily to the exit site. The study design was a prospective randomized trial, controlling for S aureus nasal carriage. Eighty-two continuous ambulatory and continuous cyclic peritoneal dialysis patients (54% male, 71 % white, 34% insulin-dependent, mean prestudy time on peritoneal dialysis 1.2 years) were randomly assigned to cyclic rifampin (n = 41 patients) or daily exit site mupirocin prophylaxis (n = 41 patients). Mean follow-up was 1 year. S aureus catheter infection rates were 0.13/yr with mupirocin and 0.15/yr with rifampin (P = NS). Both rates were significantly lower than the center's historical rate (the period between 1983 and 1992) of 0.46/yr prior to the study (P < 0.001). S aureus peritonitis rates were 0.04/yr with mupirocin and 0.02/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.16/yr (P < 0.02). Catheter loss due to S aureus infections was 0.02/yr with mupirocin and 0/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.12/yr (P < 0.001). There were no side effects in patients using mupirocin, but 12% were unable to continue rifampin due to side effects. We conclude that mupirocin ointment at the exit site and cyclic oral rifampin are equally effective in reducing S aureus catheter infections. In addition, rifampin or mupirocin significantly reduced S aureus peritonitis and catheter loss due to S aureus infections. Mupirocin at the exit site provides an excellent alternative prophylaxis for S aureus infections, particularly in patients who cannot tolerate oral rifampin therapy.", "Exit site infection is a major risk factor for the development of peritonitis in continuous ambulatory peritoneal dialysis. The frequency of infection can be reduced by scrupulous exit site care with or without topical antiseptics. A randomized trial was performed of 149 catheters in 130 patients to assess any additional benefits conferred by the use of povidine iodine dry powder spray at dressing changes over an existing strict protocol of exit care. Exit infections occurred in 14 (18%) of 77 patients using spray and in 15 (21%) of 72 patients not using spray. The risk of peritonitis was also similar in each group. The proportion of infections caused by Staphylococcus aureus was reduced in the spray group, but those caused by Pseudomonas aeruginosa were increased. Rash occurred in 6% of those using the spray. The use of the spray did not therefore seem justified.", "Infections are the main complications of peritoneal dialysis, and currently there is no established method for prevention. A prospective, randomized, single-blind study was performed to evaluate the efficacy of regular application of povidone-iodine ointment at the catheter site (during the entire time on the study) in peritoneal dialysis. One hundred twenty patients were randomized; three were excluded for not completing the study. Sixty-one patients received application of povidone-iodine and 56 patients received standard care. Povidone-iodine ointment was effective in delaying infectious complications, with a lower proportion of treated patients having infections (exit site and peritonitis) within 140 days of starting dialysis compared with the controls (P = 0.04, Wilcoxon test). This protective benefit was lost after 140 days on dialysis. Staphylococcus aureus infections developed in only two (3.3%) of the treated patients compared with 10 (21.4%) of the controls (P = 0.009), despite the higher rate of S aureus nasal carriage in the treated group (22 of 61 patients [36%] v 14 of 56 patients [25%]).", "We assessed the efficacy of preoperative antibiotic prophylaxis in a prospective trial for patients undergoing insertion of Tenckhoff catheters for continuous ambulatory peritoneal dialysis (CAPD). The prophylactic regimen was a single dose of cefazolin (500 mg) and gentamicin (80 mg) given intravenously half an hour before surgery. There was no significant difference in the number of exit site infections (8 in the antibiotic group vs. 8 in the controls) and the number of episodes of peritonitis (5 in the antibiotic group vs. 2 in the controls). Our study showed that prophylactic preoperative antibiotics did not reduce the number of exit site infections and peritonitis after the insertion of Tenckhoff catheters.", "In the interest of studying the prevention of chronic peritoneal dialysis infections, serial studies of the bacterial epidemiology in peritonitis and of antibiotic prophylaxis, respectively, were carried out. For 18 months, prospective evaluation of catheter exist site cultures, performed at the time patients developed acute peritonitis, showed that Staphylococcus aureus peritonitis was associated with concordant S. aureus at the exist site in 85% of cases, significantly more frequent than that for other organisms (P less than 0.02). Furthermore, active inflammation along with concordant culture results at the exit site characterized more than 60% of S. aureus peritonitis cases, also significantly more than that for other organisms (P less than 0.01). Over the ensuing 2 yr, patients beginning chronic peritoneal dialysis with a new percutaneously placed catheter were prospectively entered into a randomized, controlled trial of long-term antibiotic prophylaxis with trimethoprim-sulfamethoxasole. Patients receiving prophylaxis tended to have fewer episodes of peritonitis; however, the lower rate of peritonitis reached statistical significance only comparing patients who were S. aureus carriers at entry into the study to patients who were not S. aureus carriers. In particular, the prophylaxis trial seemed to reduce the specific incidence of S. aureus peritonitis overall, with S. aureus appearing in only 2 of 28 total peritonitis episodes among treated patients as compared with 11 of 37 total episodes among non-treated patients (P less than 0.01). Further analysis of the time to first peritonitis suggests that the effect of prophylaxis was most prominent during the first 3 months of therapy (P less than 0.02) rather than later in the course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "A total of 127 patients from 8 hospitals were randomized into 1 of 2 exit-site care regimes to evaluate their effect on rate of exit-site infection (ESI). Group 1 used povidone iodine and nonocclusive dressings changed 2 to 3 times weekly; Group 2 simply cleansed the exit site with nondisinfectant soap and water. Incidence, cause, duration, and treatment of ESI and peritonitis (P) were noted. Groups were analysed for age, sex, end-stage renal disease (ESRD), catheter, and systems. Total cumulative follow up time was 95.6 years. There was a significantly higher rate (p = 0.0183) of ESI in Group 2 (soap and water). The mean rate of ESI was 0.27 episodes/patient year for Group 1 versus 0.71 episodes/patient year for Group 2. Rates of P for the two groups were not significantly different (p greater than 0.50): 0.446 episodes/year for Group 1 versus 0.574 episodes/year for Group 2. S. aureus was responsible for 83% of ESI in Group 1 and 67% of ESI in Group 2. Protective dressing with a disinfectant is associated with significantly less ESI than minimum care. However, further research in exit-site care aimed specifically at reducing S. aureus infection is still required.", "Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients. Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population, we studied the effect of intermittent rifampin, an antibiotic known to decrease S aureus nasal carriage, on catheter-related infections and peritonitis. We randomly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment. The rifampin-treated patients had a significant delay in time to first catheter-related infection (P less than 0.015) and significantly fewer catheter-related infections overall (P less than 0.001). The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients. Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections. There was no significant difference in peritonitis rates between groups, although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients. Adverse effects necessitated withdrawal of rifampin in four patients. We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population.", "The effectiveness of sodium fusidate and ofloxacin to eliminate nasal and catheter exit-site Staphylococcus aureus colonization and to prevent infections was compared in 31 patients on continuous ambulatory peritoneal dialysis (CAPD). In a prospective randomized study, 9 patients were treated with topical 2% sodium fusidate ointment applied in the anterior nares and in the pericatheter skin twice daily for 5 days; 9 subjects received oral ofloxacin 200 mg taken every 48 hours for 5 days and 13 subjects were in the control group. Treatment courses were repeated at one-month intervals. Mean duration of follow-up was 7.8 months (242 patients-month). Follow-up samples from the nares and the catheter exit-site were obtained every month from all participants to determine the presence of S. aureus. Development of S. aureus exit-site infection and peritonitis were assessed. During the study, S. aureus was recovered from 45%, 59% and 52% of the samples from the nares and/or exit-site in the sodium fusidate, ofloxacin and control groups, respectively (p = 0.13). S. aureus grew less frequently (p < 0.01) in samples from the exit-site in the sodium fusidate than in the other two groups. Eradication of nasal colonization (two negative cultures within one month) was observed in 43%, 40% and 33% of the cases in the sodium fusidate, ofloxacin and control groups, respectively (p > 0.50). The corresponding figures for exit-site eradication were 43%, 33% and 11%, respectively (p = 0.34). Twenty-four S. aureus-associated infection episodes (12 of exit-site and 12 of peritonitis) were diagnosed in 16 of the 31 patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "A total of 1144 patients receiving continuous ambulatory peritoneal dialysis in nine European centers was screened for nasal carriage of Staphylococcus aureus. Two hundred sixty-seven subjects were defined as carriers of S. aureus by having had at least two positive swab results from samples taken on separate occasions, and were randomly allocated to treatment or control groups. Members of each group used a nasal ointment twice daily for 5 consecutive days every 4 wk. The treatment group used calcium mupirocin 2% (Bactroban nasal; SmithKline Beecham, Welwyn Garden City, United Kingdom) and the control group used placebo ointment. Patients were followed-up for a maximum period of 18 months. There were 134 individuals in the mupirocin group, and 133 individuals acted as control subjects. There were no differences in demographic data, cause of renal failure, type of catheter, system used, or method of exit-site care between the groups. Similarly, there were no differences in patient outcome or incidence of adverse events between both groups. Nasal carriage fell to 10% in those subjects who received active treatment and 48% in those who used the placebo ointment. There were 55 exit-site infections in 1236 patient-months in the control group and 33 in 1390 patient-months in the treatment group (not significant). S. aureus caused 14 episodes of exit-site infection in the mupirocin group and 44 in the control group (P = 0.006, mixed effects Poisson regression model). There were no differences in the rate of tunnel infection or peritonitis. There was no evidence of a progressive increase in resistance to mupirocin with time. Regular use of nasal mupirocin in continuous ambulatory peritoneal dialysis patients who are nasal carriers of S. aureus significantly reduces the rate of exit-site infections that occurs because of this organism.", "124 stable CAPD patients from 8 Australian and 3 New Zealand centers were randomly assigned in a blinded fashion to one of two groups to study the effect of vaccination using commercial preparations consisting of a combined staphylococcus toxoid and whole killed staphylococci (SB) or normal saline solution (SS) on the incidence of peritonitis and exit site infection and S. aureus nasal carriage over a 12-month prospective period. In addition, levels of IgG, IgA, IgM, C3 and C4 were monitored during the trial period in serum and dialysate; serum levels of anti-alpha hemolysin and dialysate levels of fibronectin and specific antistaphylococcal antibodies were also measured. Over the period, treatment with SB or SS did not affect the incidence of peritonitis, catheter-related infection or S. aureus nasal carriage. However, vaccination with SB elicited a significant increase in the level of serum anti-alpha hemolysin throughout the 12 month duration of the study, although the level of increase was unrelated to the subsequent rate of peritonitis. Vaccination with SB but not SS elicited a significant increase in the dialysate level of specific antibodies against S. aureus. Serum levels of IgG, IgA, IgM, complement C3 and C4 were within the normal range in the CAPD patients studied and remained unaffected by vaccination with SB. In addition, dialysate levels of IgG, IgA, IgM, complement C3 and C4 were 50-100 times lower than corresponding serum levels and remained unaffected by vaccination. In summary, immunisation with an anti-staphylococcal agent was not successful in reducing peritonitis or exit site infection in CAPD patients.", "The role of vancomycin and other antibiotics in the treatment of acute peritonitis in peritoneal dialysis (PD) patients is well established. However, the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed PD catheters remains controversial. We performed a prospective randomized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of postoperative peritonitis. Over a 6-year period, 221 patients undergoing 254 permanent peritoneal catheter placement procedures were randomized into three groups. Group I patients (86 procedures) were administered a single intravenous (IV) dose of vancomycin, 1,000 mg, 12 hours before peritoneal catheter placement procedures, whereas group II patients (85 procedures) were administered a single IV dose of cefazolin, 1,000 mg, 3 hours before the procedure. Group III patients (83 procedures) were not administered antibiotics preoperatively for at least 1 week before the procedure. Patients were monitored for peritonitis in the following 14 days. Peritonitis developed in 1 patient (1%) in group I (vancomycin group) and 6 patients (7%) in group II (cefazolin group) compared with 10 patients (12%) in group III (control group); P = 0.02. We conclude that the use of preoperative single-dose IV vancomycin prophylaxis for permanent PD catheter placement reduces the risk for postoperative peritonitis. Single-dose vancomycin is superior to single-dose cefazolin in reducing the risk for postoperative peritonitis. Absence of prophylaxis is associated with a high risk for developing postoperative peritonitis.", "When a peritoneal dialysis catheter is inserted intra-abdominally in a patient starting peritoneal dialysis (PD) there is always a risk for postoperative wound infection and peritonitis. At our centre, PD is started immediately after the dialysis catheter is inserted. This may increase the postoperative risk for peritonitis and wound infection. The aim of this prospective, randomized, study was to evaluate whether the incidence of microbial growth postoperatively (within 10 days) after catheter insertion could be reduced by prophylactic antibiotic therapy.\n During a period of 27 months, 38 patients, who consecutively entered the PD programme, (11 women and 27 men, mean age 57 years) were included in the study. Eighteen patients were given cefuroxime 1.5 g i.v. preoperatively and 250 mg i.p. in the first dialysis bag (containing 1 litre fluid) as prophylaxis. Twenty patients were not given prophylactic antibiotics (control group). All catheter insertions were performed in an operating theatre by the same surgeons using the same technique.\n In the test group, none of the patients showed microbial growth in the dialysis fluid during the post-operative period, while in the control group six of 20 patients (30%) suffered from such growth (P = 0.021).\n Prophylactic treatment by cefuroxime i.v. pre- and i.p. perioperatively may reduce the risk for microbial growth and peritonitis after insertion of a Tenckhoff catheter.", "We have studied the efficacy of topical Mupirocin for elimination of Staphylococcus aureus (Staph. aureus) nasal carriage in CAPD patients. Staph. aureus nasal carriers in our CAPD program were randomized to one of two groups: Group 1, treated with Mupirocin, and Group 2, treated with neomycin sulphate nasal ointment. The prevalence of Staph. aureus nasal colonization was 44% for patients (24/54) and 17% for dialysis partners (5/29). Group 1 included 11 patients and 1 partner, and Group 2, 8 patients and 2 partners. In Group 1, the eradication rate was 100%, and the recolonization rate was 0, 8, 41, 55 and 66% at 1, 2, 3, 6 and 10 months. In Group 2, the eradication rate was 40%, with a recolonization rate of 0.25 and 75% at 1, 2 and 3 months. Re-treatment with mupirocin was successful in 66% of the cases, compared to 20% for neomycin. The MIC90 of mupirocin for Staph. aureus was 0.5 mcg/mL, with an increase to 4 mcg/mL towards the end of the study. During the study period, there was a very low incidence of Staph. aureus peritonitis or catheter-related infections in patients treated with mupirocin. Secondary effects of mupirocin were negligible. Mupirocin is more effective than neomycin sulphate for the elimination of Staph. aureus nasal colonization in patients undergoing CAPD. Periodic re-treatment is frequently necessary, given the significant recolonization rate.", "nan", "A prospective randomized study of the prevention of candida peritonitis (CP) in continuous ambulatory peritoneal dialysis patients using oral nystatin given concomitantly with antibiotic therapy was carried out for 2 years. Patients were randomized into two groups. Nystatin tablets 500,000 units four times a day were given to group 1 but not group 2 patients whenever antibiotics were prescribed. There were 199 patients at risk (mean follow-up, 18.0 months) in group 1 and 198 patients at risk (mean follow-up, 16.6 months) in group 2. The peritonitis and antibiotic prescription rates were comparable between the two groups. There were four episodes of CP in four patients in group 1 and 12 episodes in 11 patients in group 2. The probability of CP-free survival at 2 years was higher in group 1 compared with group 2 (0.974 v 0.915; P < 0.05). However, only three (75%) CP episodes in group 1 and six (50%) in group 2 were considered \"antibiotics related.\" The incidence of antibiotics-related CP was 1.39 and 3.19 per 100 peritonitis episodes and 0.66 and 1.43 per 100 antibiotic prescriptions in groups 1 and 2, respectively (P = NS). We conclude that oral nystatin prophylaxis with each antibiotic prescription reduced the rate of CP in patients on continuous ambulatory peritoneal dialysis irrespective of its apparent temporal relationship to antibiotic prescription." ]

[ "2606162" ]

[ "The effectiveness of a prenatal education programme for the prevention of congenital toxoplasmosis." ]

[ "A 10 min education programme was developed which, if effective in changing the behaviour of pregnant women, would eliminate or greatly reduce the risk of congenital toxoplasmosis. It was taught in 26 randomly selected (case) prenatal classes offered to women early in their pregnancy. The remaining 26 (control) classes received routine class material which did not mention toxoplasmosis. A questionnaire was administered to all women prior to this early class (pre-test) and again after the last prenatal class, held just prior to delivery (post-test). Changes in pet, food and personal hygiene behaviour between the pre- and post-test were determined and a score calculated by adding points for change towards those behaviours recommended in the programme and subtracting points for change in the opposite direction. Cat owners in case classes had a significantly higher score in pet hygiene behaviour than those in control classes (P less than 0.05). No significant difference was found between the food or personal hygiene scores of women in case and control classes, possibly because of low power. However, although behaviours did not differ on the pre-test, women in case classes had significantly better cooking methods for roast beef and hamburger on the post-test (P less than 0.05 and P less than 0.01 respectively). It is concluded that this programme is effective and should be offered to all women in order to reduce congenital toxoplasmosis incidence." ]

[ "17920715", "14511925", "1480768", "11439206", "9288839", "16782926", "10924966", "1869454", "9288840", "11830307", "10799721", "3542916", "11054514", "12504039", "9165135" ]

[ "Five year results of a randomized trial comparing hyperfractionated to conventional radiotherapy over four weeks in locally advanced head and neck cancer.", "Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial.", "Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy.", "A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study.", "Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial.", "Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial.", "A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003.", "Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma.", "A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer.", "A multicentre randomized/controlled trial of a conventional versus modestly accelerated radiotherapy in the laryngeal cancer: influence of a 1 week shortening overall time.", "Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer - report on 3-year tumour control and normal tissue toxicity.", "Hyperfractionated photon radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, pharynx, larynx, and sinuses, using radiation therapy as the only planned modality: (preliminary report) by the Radiation Therapy Oncology Group (RTOG).", "Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancers.", "Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy--a multicenter randomized trial.", "A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer." ]

[ "Fractionation strategies delivered over 4 weeks are of clinical and radiobiological interest because treatment is completed before radiotherapy (RT) induced clonogen proliferation commences in earnest approximately 3 to 4 weeks into a course of RT. We wished to test the clinical hypothesis that an increased total dose delivered over 4 weeks with smaller than standard doses per fraction in locally advanced squamous cell carcinoma (SCC) may result in relative protection of late responding tissues and an increased tumor control compared to a conventional daily course in the same overall time.\n Between 1988 and 1995 a randomized controlled trial employing RT alone was undertaken at the Princess Margaret Hospital that included 331 eligible patients with T3 or T4 N0 or any N-positive oropharynx, hypopharynx, or larynx primary SCC. RT was randomly assigned to one of two 4 week schedules, either 51 Gy in 20 equal daily fractions, termed conventional fractionation (CF), or 58 Gy in 40 equal fractions given twice per day as a hyperfractionated (HF) experimental arm.\n The 5-year local relapse rate was reduced in the HF (41%) compared to the CF arm (49%). This difference was marginally not significant (p=0.082) when the effect was not adjusted. When the effect of the treatment was adjusted by Cox model for clinical factors that included N-category, ECOG performance status, site of disease, T-category, age, hemoglobin, and gender the HF achieved a significant effect (p=0.02). Survival (40% vs. 30%) was also improved with HF compared to CF arm. This difference was only marginally not significant (p=0.069) but again achieved statistical significance when the model was adjusted for clinical factors (p=0.01). Similar results were observed for disease free survival. Although reversible acute toxicity was increased with HF, the overall 5-year rate of grade 3 and 4 late toxicity for the CF was 10.5% compared to 7.7% in the higher dose HF arm.\n HF delivered in 4 weeks permits enhanced RT doses achieving improved tumor control, without increased late toxicity, compared to daily fractionated radiotherapy in the same overall time.", "Although head and neck cancer can be cured by radiotherapy, the optimum treatment time for locoregional control is unclear. We aimed to find out whether shortening of treatment time by use of six instead of five radiotherapy fractions per week improves the tumour response in squamous-cell carcinoma.\n We did a multicentre, controlled, randomised trial. Between January, 1992, and December, 1999, of 1485 patients treated with primary radiotherapy alone, 1476 eligible patients were randomly assigned five (n=726) or six (n=750) fractions per week at the same total dose and fraction number (66-68 Gy in 33-34 fractions to all tumour sites except well-differentiated T1 glottic tumours, which were treated with 62 Gy). All patients, except those with glottic cancers, also received the hypoxic radiosensitiser nimorazole. Analysis was by intention to treat.\n More than 97% of the patients received the planned total dose. Median overall treatment times were 39 days (six-fraction group) and 46 days (five-fraction group). Overall 5-year locoregional control rates were 70% and 60% for the six-fraction and five-fraction groups, respectively (p=0.0005). The whole benefit of shortening of treatment time was seen for primary tumour control (76 vs 64% for six and five fractions, p=0.0001), but was non-significant for neck-node control. Six compared with five fractions per week improved preservation of the voice among patients with laryngeal cancer (80 vs 68%, p=0.007). Disease-specific survival improved (73 vs 66% for six and five fractions, p=0.01) but not overall survival. Acute morbidity was significantly more frequent with six than with five fractions, but was transient.\n The shortening of overall treatment time by increase of the weekly number of fractions is beneficial in patients with head and neck cancer. The six-fractions-weekly regimen has become the standard treatment in Denmark.", "EORTC protocol 22791 compared once daily fractionation (CF) of 70 Gy in 35-40 fractions in 7-8 weeks, to pure hyperfractionation (HF) of 80.5 Gy in 70 fractions in 7 weeks using 2 fractions of 1.15 Gy per day, in T2-T3 oropharyngeal carcinoma (excluding base of tongue), N0,N1 of less than 3 cm. From 1980 to 1987, 356 patients were entered. In the final analysis (June 1990), the local control was significantly higher (p = 0.02 log-rank) after HF compared with CF. At 5 years, 59% of patients are local disease-free in the HF arm compared to 40% in the CF arm. The superiority of HF was demonstrated in patients staged T3N0,T3N1 but not in T2. The Cox model confirmed that the treatment regimen was an independent significant prognostic factor for locoregional control (p = 0.007 log-rank). This improvement of locoregional control was responsible for a trend to an improved survival (p = 0.08 log-rank). There was no difference in late normal tissue damage between the two treatment modalities.", "The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx.\n Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached.\n The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms.\n Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy.", "A 5 week-hyperfractionated and accelerated radiotherapy regimen without reduction of the total dose was developed to fight tumour repopulation during treatment and tumour hypoxia. The purpose of the study was to try to improve loco-regional control in high risk head and neck carcinoma treated with curative radiotherapy.\n From 1985 to 1995, a randomised controlled trial of the EORTC Cooperative Group of Radiotherapy (EORTC 22851) compared the experimental regimen (72 Gy/45 fractions/5 weeks) to standard fractionation and overall treatment time (70 Gy/35 fractions/7 weeks) in T2, T3 and T4 head and neck cancers (hypopharynx excluded). The end-point criteria were local and loco-regional control, overall and disease-free survival, and acute and late toxicities. Five hundred twelve patients were accrued.\n Patients in the AF (accelerated fractionation) arm did significantly better with regard to loco-regional control (P = 0.02) resulting at 5 years in a 13% gain (95% CI 3-23% gain) in loco-regional control over the CF (conventional fractionation) arm. This improvement is of larger magnitude in patients with poorer prognosis (N2-3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent prognostic factor of good prognosis for loco-regional control (P = 0.03). Specific survival shows a trend (P = 0.06) in favour of the AF arm. ACUTE AND LATE TOXICITIES: Acute and late toxicity were increased in the AF arm. Late severe functional irradiation damage occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord.\n This trial shows that accelerated radiotherapy improves loco-regional control in head and neck squamous cell carcinomas. A less toxic scheme should, however, be investigated and documented before using accelerated radiotherapy as a standard regimen of curative radiotherapy for head and neck cancers.", "With the aim to increase the dose intensity of radiation therapy (RT), and subsequently the locoregional control rate, a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma (HNSCC).\n Between 1994 and 1998, 268 patients with T3 or T4, N0 to N3 HNSCC (staged by 1997 International Union Against Cancer criteria) that was not eligible for surgery were randomly assigned to receive either conventional RT, delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days, or to receive very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days (2 Gy/fraction bid).\n The most common tumor site was the oropharynx and most of the patients (70%) had T4 and N1 to N3 tumors in 72% of patients. The main patient and tumor characteristics were well-balanced between the two arms. The median total doses were 63 Gy (accelerated) and 70 Gy (conventional), with a median overall time of 22 days and 48 days, respectively. Acute mucositis was markedly increased in the accelerated-RT arm (P < .001). The locoregional control rate was improved by 24% at 6 years with accelerated RT. In contrast, disease-free survival and overall survival were not significantly different between the two arms. There was no difference in late effects between the two arms.\n The very accelerated RT regimen was feasible and provided a major benefit in locoregional control but had a modest effect on survival.", "The optimal fractionation schedule for radiotherapy of head and neck cancer has been controversial. The objective of this randomized trial was to test the efficacy of hyperfractionation and two types of accelerated fractionation individually against standard fractionation.\n Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1. 2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5 days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patients were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive.\n Patients treated with hyperfractionation and accelerated fractionation with concomitant boost had significantly better local-regional control (p = 0.045 and p = 0.050 respectively) than those treated with standard fractionation. There was also a trend toward improved disease-free survival (p = 0.067 and p = 0.054 respectively) although the difference in overall survival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionation. All three altered fractionation groups had significantly greater acute side effects compared to standard fractionation. However, there was no significant increase of late effects.\n Hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally advanced head and neck cancer. Acute but not late effects are also increased.", "From April 1986 to May 1989, 112 patients seen at a single institution with previously untreated squamous cell oropharynx carcinoma, Stages III and IV, were randomly assigned to 66 Gy in 33 fractions of 2 Gy each (conventional RT) versus 70.4 Gy in 64 fractions of 1.1 Gy given twice a day with a minimal interfraction interval of 6 hours (hyperfractionated RT). The overall time for both arms was 6 1/2 weeks. Patients were stratified by site (base of the tongue vs others), T stage (T1/T2 vs T3 vs T4), N stage (N0/N1 vs N2 vs N3), and lymphnode size (less than 6 cm vs greater than 6 cm). As of January 1990, an analysis was performed in 98 patients (8 patients in the conventional arm and 6 in the hyperfractionation not included). The groups were balanced by age, performance status, stage, and site of the primary disease. The median follow-up time was 25 months. The probability of complete loco-regional response was 62% in the hyperfractionation arm and 52% for the conventional fractionation (p = 0.28). There was no difference in the control of lymphnodal disease (hyperfractionated = 55%, conventional = 57%; p = 0.92), but the disease control in the oropharynx only was significantly improved in the hyperfractionation arm (84% vs 64%, p = 0.02). Overall survival rate at 42 months was 27% for the hyperfractionation arm and 8% for the conventional (p = 0.03). Survival rates for hyperfractionated versus conventional RT were 40% versus 18% (p = 0.06), respectively, for Stage III patients and 16% versus 0% (p = 0.15), respectively, for Stage IV. There was significant improvement in survival in favor of the hyperfractionation arm in patients with lesions outside the base of the tongue (31% vs 15%, p = 0.02), for those with a 50-70% Karnofsky status (19% vs 0%, p = 0.006) and for patients with N0/N1 disease (38% vs 15%, p = 0.03). Acute toxicities were of similar magnitude, although both skin and mucosal reactions appeared earlier on the hyperfractionation scheme. To date, no differences in late toxicity have been observed. We conclude that in a subset group of patients with locally advanced carcinoma of the oropharynx, hyperfractionated radiotherapy appears to provide improved survival without adding to increased toxicity.", "Continuous, hyperfractionated, accelerated radiotherapy (CHART) has shown promise of improved tumour control and reduced late morbidity in pilot studies and has now been tested in a multicentre randomised controlled clinical trial.\n Patients with squamous cell cancer in the main sites within the head and neck region with the general exception of early T1 N0 tumours were entered into the study by 11 centres. There was a 3:2 randomisation to either CHART, where a dose of 54 Gy was given in 36 fractions over 12 days, or to conventional therapy where 66 Gy was given in 33 fractions over 6.5 weeks. A total of 918 patients were included over a 5 year period from March 1990.\n ACUTE MORBIDITY: Acute radiation mucositis was more severe with CHART, occurred earlier but settled sooner and was in nearly all cases healed by 8 weeks in both arms. Skin reactions were less severe and settled more quickly in the CHART treated patients. TUMOUR CONTROL AND SURVIVAL: Life table analyses of loco-regional control, primary tumour control, nodal control, disease-free interval, freedom from metastasis and survival showed no evidence of differences between the two arms. In exploratory subgroup analyses there was evidence of a greater response to CHART in younger patients (P = 0.041) and poorly differentiated tumours appeared to fare better with conventional radiotherapy (P = 0.030). In the larynx there was evidence of a trend towards increasing benefit with more advanced T stage (P = 0.002). LATE TREATMENT RELATED MORBIDITY: Osteoradionecrosis occurred in 0.4% of patients after CHART and 1.4% of patients after conventional radiotherapy. The incidence of chondritis or cartilage necrosis was similar in both arms. Life table analysis showed evidence of reduced severity in a number of late morbidities in favour of CHART. These were most striking for skin telangiectasia, superficial and deep ulceration of the mucosa and laryngeal oedema.\n Similar local turnout control was achieved by CHART as compared with conventional radiotherapy despite the reduction in total dose from 66 to 54 Gy supporting the importance of repopulation as a cause of radiation failure. The effects seen in advanced laryngeal cancer and those related to histological differentiation need further study. Reduced late morbidity is a factor which together with patient preference should be considered in the decision as to the programme of radiotherapy to employ in the curative treatment of head and neck cancer.", "To compare in a phase III study the loco-regional control, disease-free survival and overall survival induced by an accelerated regimen (AF) as compared with conventional regimen (CF) and to analyze the early and late post-radiation morbidity in both arms.\n Patients with age < or = 75, WHO 0-1, suitable for a radical course of radiotherapy T1-T3, N0, M0, stage of glottic and supraglottic laryngeal cancer were randomized to either CF: 66Gy given in 33 fractions over 45 days or AF: 66Gy given in 33 fractions over 38 days (2 fractions every Thursday). A total of 395 patients were included from 05.1995 to 12.1998.\n Early toxicity: At the end of radiotherapy patients treated with AF complained for more severe reactions than patients treated with CF. In 8 weeks after treatment completion patients treated with AF complained only for more severe pain on swallowing (P=0.027). In 4 months after treatment completion all types of toxicity except for skin teleangiectasia (P=0.001) were similar in the two groups. Loco-regional control: comparison between CF and AF showed no difference in terms of loco-regional control (P=0.37).\n The improvement in AF in terms of loco-regional control is estimated to be 3-5% in comparison with conventional regimen and is not significant. The intensity of reactions after 4 months was similar in both arms, what suggests the possibility of further shortening of the overall time by few days or enhancing the total dose within the limits of acceptable morbidity.", "To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation (CAIR) compared to a conventional treatment (5 days per week) in a randomized trial.\n One hundred patients with squamous cell carcinoma of the head and neck in stage T(2-4)N(0-1)M(0) were entered into the trial between December 1, 1993 and June 30, 1996. Dose per fraction of 2.0 Gy (to the end of 1994), and 1.8 Gy (since January 1, 1995) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66-72 Gy (depending on tumour stage). The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm.\n Actuarial 3-year local tumour control was 82% in the CAIR and 37% in the control group (P<0.0001) with reduction in local recurrence rate of 83%. Actuarial 3-year overall survival was 78 and 32% (P<0.0001), respectively. Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm. After 2.0 Gy fractions five of 23 patients (22%) in the CAIR developed early necroses over a period of 2-4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions (CLE). For this reason dose per fraction was lowered to 1. 8 Gy and the CLE was not observed again until now. Thus the overall rate of CLE decreased to 10%.\n The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends. A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation, however tolerable by patients. Relatively high rate (22%) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy.", "From August 1979 to June 1983, the RTOG conducted a prospective Phase III study that compared a standard schedule with five fractions per week of 180 to 200 cGy per day to a total dose of 6600-7380 cGy, with a hyperfractionation regimen consisting of two fractions of 120 cGy per day, separated by a rest period of 3 to 6 hours for a total of 6000 cGy. A total of 210 patients were entered, of which 187 are analyzed. Complete initial tumor clearance in the head and neck was achieved by radiotherapy in 61% of the patients assigned to the standard schedules and in 59% of those assigned to the continuous hyperfractionation schedule; surgical salvage contributed towards achieving complete response in 5% and 7% of patients, respectively. The Kaplan-Meier estimates for loco-regional control of tumor at 1 and 2 years was 39% and 29% for the standard schedules, and 43% and 30% for the hyperfractionation schedule. The endpoints examined to evaluate therapeutic effects do not indicate that the stated hyperfractionation schedule is different than the standard RTOG treatment schedule for head and neck cancer. Acute normal tissue reactions appear to be more severe with the hyperfractionation schedule but the incidence of late reactions is similar in both groups. There is a tendency toward more severe acute reactions when the interval between the two fractions per day is 4.5 hrs or less in comparison to intervals longer than 4.5 hrs.", "Radiation therapy is often the primary treatment for advanced cases of head and neck cancers not considered suitable for radical surgery. In these cases locoregional tumour control rates are low and has warranted innovative treatment modifications, such as altered fractionation schedules and combination with chemotherapy.\n From October 1990 to December 1997, 239 patients with squamous cell cancers originating in the head and neck region were randomized to one of three treatment options. Standard therapy consisting of conventional fractionation with 70 Gy in 7 weeks in 35 fractions (CF). The second treatment option consisted of a continuous hyperfractionated accelerated radiotherapy delivering a total dose of 55.3 Gy in 33 fractions over 17 consecutive days (V-CHART). The third study arm had identical fractionation and dose as the above accelerated treatment, with the additional administration of 20 mg/m(2) mitomycin C (MMC) on day 5 of treatment (V-CHART+MMC).\n Main toxicity resulted from accelerated fractionation in confluent mucositis (Grade 3-4 in 95%) requiring nasogastral tube feeding, analgetics and antiphlogistics in the majority of cases. Haematological toxicity Grade 3-4 was seen after MMC administration in 18%. MMC administration did not influence mucosal reaction. Overall duration of mucositis was not different in the three treatment groups. Loco-regional tumour control was 31% after CF, 32% after V-CHART and 48% after V-CHART+MMC, respectively (P<0.05). Overall crude survival was 24% after CF, 31% following V-CHART and 41% after V-CHART+MMC, respectively (P<0.05). Median follow up was 48 months (assessment performed in February 1999).\n Following shortening overall treatment time from 7 weeks to 17 consecutive days and dose of radiotherapy from 70 to 55.3 Gy the results in the radiotherapy only treated patients are identical. A significant improvement regarding local tumour control and survival was seen following administration of MMC to the accelerated fractionated treatment.", "To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx.\n Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week).\n No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms.\n The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity.", "To study the effect of accelerated radiation treatment in locally advanced head and neck cancer, a prospective randomised trial was conducted comparing two fractionation schemes which differed only in the overall treatment time; fraction size and total dose were the same in both arms.\n Eighty-two patients with stage 3 or 4 squamous cell cancer of the oral cavity, oropharynx, hypopharynx or larynx considered suitable for radical radiotherapy as primary treatment were stratified by site and stage and randomised to receive 66 Gy in 33 2 Gy daily fractions in 45-48 days (o.d.) or 66 Gy in 33 2 Gy twice daily fractions in 22-25 days (b.i.d.).\n An initial improved clinical response in tumour control in the b.i.d. arm was not sustained and the 3 year recurrence free survival and overall survival rates were similar and not significantly different. The actuarial recurrence free survival was 49.1% in the b.i.d. arm and 44.3% in the o.d. arm. The disease free 3 year survival was 59.4% and 56.8%, respectively. The acute and late normal tissue effects were scored using the RTOG scale. As expected the acute effects were much greater in the b.i.d. arm. The combined grade 3 and 4 late effects were similar but the proportion of grade 4 reactions was significantly higher in the b.i.d. arm. The increase in grade 4 toxicity caused the trial to be discontinued after 82 of the planned 226 patients had been randomised.\n The severity of the normal tissue effects and a failure to demonstrate sustained local control does not support this fractionation scheme in patients with such extensive head and neck cancer." ]

[ "18971490", "18035140", "1919895" ]

[ "Early insulin therapy in very-low-birth-weight infants.", "Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants.", "Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate." ]

[ "Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.\n In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm.\n As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04).\n Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)\n 2008 Massachusetts Medical Society", "To investigate the use of insulin throughout the first week of life in very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the dominant hormone involved in fetal growth, and low levels have been implicated in neonatal morbidities, such as retinopathy of prematurity.\n In this pilot randomized controlled study (n = 16), the intervention group received insulin (0.025 U/kg/hr) on days 1 to 7, with 20% dextrose to maintain normoglycemia. Control infants received standard neonatal care. All infants received continuous glucose monitoring.\n The intervention and standard care groups had similar mean gestational age (+/- standard deviation), 26.2 (+/- 2.5) vs 26.9 (+/- 2.7) weeks, and birth weight, 0.79 (+/- 0.26) vs 0.73 (+/- 0.16) kg. The standard care infants were hyperglycemic (sensor glucose >10 mmol/L [180 mg/dL]) for 35.9% of the study period, compared with 7.6% for the insulin-treated infants (P = .035). The duration of time with hypoglycemia (<2.6 mmol/L [47 mg/dL]) did not differ between the 2 groups (P = .746). The insulin-treated group had a 2.4-fold increase in mean IGF-I bioactivity (P = .005).\n Early insulin therapy improves blood glucose control and increases IGF-I bioactivity levels. This could result in less morbidity associated with hyperglycemia and reduced IGF-I levels.", "To investigate lipid tolerance in sick, ventilator-dependent, very low birth weight infants from the first day of life and the effects of early introduction of intravenously administered lipid (IVL) on glucose homeostasis.\n Twenty-nine infants in the neonatal intensive care unit with birth weight less than 1500 gm received isocaloric, isonitrogenous parenteral feedings from day 1 with either IVL, 1 gm/kg from day 1 to 3 gm/kg from day 4 (group I; n = 16), or IVL added only from day 8 (group II; n = 13). Possible adverse clinical effects were monitored. Blood metabolites, nonesterified fatty acids, serum triglycerides, and insulin levels were determined daily. Arterial blood gases were measured and changes in partial pressures of oxygen and of carbon dioxide in arterial blood were compared between the two groups.\n Early lipid infusion did not appear to have deleterious effects on blood gas tensions or to increase respiratory morbidity. The incidence of other adverse clinical effects that may be associated with IVL was not increased by earlier introduction of lipid. Serum lipid values were comparable to those of preterm infants receiving IVL at a later postnatal age. Blood glucose concentrations were higher in group II (mean, 7.50 (SEM 0.43) mmol/L) than in group I (mean, 6.01 (SEM 0.28) mmol/L; p less than 0.05). There was no evidence of increased gluconeogenesis in infants in group I and no correlation between blood glucose concentrations and serum nonesterified fatty acid concentrations.\n When given infusion rates not exceeding 0.15 gm/kg/hr, sick, very low birth weight infants can tolerate IVL with stepwise dose increases from the first day of life without an increased incidence of possible adverse effects." ]

[ "19023429", "18091987", "21330907", "20643915", "20851460", "19059048", "18213382", "18669425" ]

[ "Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria.", "SAVVY (C31G) gel for prevention of HIV infection in women: a Phase 3, double-blind, randomized, placebo-controlled trial in Ghana.", "Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women.", "Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women.", "PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial.", "Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial.", "SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria.", "Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission." ]

[ "This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection.\n This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1:1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events.\n The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10) than on placebo (13), a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3-1.8; p = 0.56). Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5-1.1; p = 0.19 for the combined STI outcome). Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported.\n Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV.\n ClinicalTrials.gov NCT00120770.", "The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.\n This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between March 2004 and February 2006 in Accra and Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection, and randomized them to SAVVY or placebo gel. Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transudate specimens and adverse events. We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group. No clinically significant differences in the overall frequency of adverse events, abnormal pelvic examination findings, or abnormal laboratory results were seen between treatment groups. However, more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in participants randomized to SAVVY and nine in participants receiving placebo. The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731), with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33, 2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve the required number of HIV infections (66) to obtain the desired study power.\n SAVVY was not associated with increased adverse events overall, but was associated with higher reporting of reproductive adverse events. Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo.\n ClinicalTrials.gov NCT00129532.", "To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission.\n Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm.\n Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up.\n The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P = 0.10) and the no gel arm (hazard ratio = 0.67, P = 0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio = 1.10, P = 0.63) and no gel control arms (hazard ratio = 1.05, P = 0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio = 0.97, P = 0.89).\n The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated.", "The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.", "Innovative prevention strategies for HIV-1 transmission are urgently needed. PRO2000 vaginal gel was efficacious against HIV-1 transmission in studies in macaques; we aimed to assess efficacy and safety of 2% and 0·5% PRO2000 gels against vaginal HIV-1 transmission in women in sub-Saharan Africa.\n Microbicides Development Programme 301 was a phase 3, randomised, double-blind, parallel-group trial, undertaken at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. We randomly assigned sexually active women, aged 18 years or older (≥16 years in Tanzania and Uganda) without HIV-1 infection in a 1:1:1 ratio to 2% PRO2000, 0·5% PRO2000, or placebo gel groups for 52 weeks (up to 104 weeks in Uganda). Randomisation was done by computerised random number generator. Investigators and participants were masked to group assignment. The primary efficacy outcome was incidence of HIV-1 infection before week 52, which was censored for pregnancy and excluded participants without HIV-1 follow-up data or with HIV-1 infection at enrolment. HIV-1 status was established by rapid tests or ELISA at screening at 12 weeks, 24 weeks, 40 weeks, and 52 weeks, and confirmed in a central reference laboratory. The primary safety endpoint was an adverse event of grade 3 or worse. Use of 2% PRO2000 gel was discontinued on Feb 14, 2008, on the recommendation of the Independent Data Monitoring Committee because of low probability of benefit. This trial is registered at http://isrctn.org, number ISRCTN 64716212.\n We enrolled 9385 of 15 818 women screened. 2591 (95%) of 2734 participants enrolled to the 2% PRO2000 group, 3156 (95%) of 3326 in the 0·5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the primary efficacy analysis. Mean reported gel use at last sex act was 89% (95% CI 86-91). HIV-1 incidence was much the same between groups at study end (incidence per 100 woman-years was 4·5 [95% CI 3·8-5·4] for 0·5% PRO2000 vs 4·3 [3·6-5·2] for placebo, hazard ratio 1·05 [0·82-1·34], p=0·71), and at discontinuation (4·7 [3·8-5·8] for 2% PRO2000 gel, 3·9 [3·0-4·9] for 0·5% PRO2000 gel, and 3·9 [3·1-5·0] for placebo gel). Incidence of the primary safety endpoint at study end was 4·6 per 100 woman-years (95% CI 3·9-5·4) in the 0·5% PRO2000 group and 3·9 (3·2-4·6) in the placebo group; and was 4·5 (3·7-5·5) in the 2% PRO2000 group at discontinuation.\n Although safe, 0·5% PRO2000 and 2% PRO2000 are not efficacious against vaginal HIV-1 transmission and are not indicated for this use.\n UK Department for International Development, UK Medical Research Council, European and Developing Countries Clinical Trials Partnership, International Partnership for Microbicides, and Endo Pharmaceuticals Solutions.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "Female-initiated HIV-prevention options, such as microbicides, are urgently needed. We assessed Carraguard, a carrageenan-based compound developed by the Population Council, for its efficacy and long-term safety in prevention of HIV infection in women.\n We undertook a randomised, placebo-controlled, double-blind trial in three South African sites in sexually-active, HIV-negative women, aged 16 years and older. 6202 participants, who were randomly assigned by a block randomisation scheme to Carraguard (n=3103) or placebo (methylcellulose [n=3099]), were instructed to use one applicator of gel plus a condom during each vaginal sex act. Participants were followed up for up to 2 years. Visits every 3 months included testing for HIV presence and pregnancy, pelvic examinations, risk reduction counselling, and treatment for curable sexually transmitted infections and symptomatic vaginal infections. The primary outcome was time to HIV seroconversion. Analysis was in the efficacy population (a subset of the intention-to-treat population, excluding participants for whom efficacy could not be assessed). This study is registered with ClinicalTrials.gov, number NCT00213083.\n For the primary outcome (time to HIV seroconversion) we analysed 3011 women in the Carraguard group and 2994 in the placebo group. HIV incidence was 3.3 per 100 woman-years (95% CI 2.8-3.9) in the Carraguard group (134 events) and 3.8 per 100 woman-years (95% CI 3.2-4.4) in the placebo group (151 events), with no significant difference in the distribution of time to seroconversion (p=0.30). The covariate-adjusted hazard ratio was 0.87 (95% CI 0.69-1.09). Rates of self-reported gel use (96.2% Carraguard, 95.9% placebo) and condom use (64.1% in both groups) at last sex acts were similar in both groups. On the basis of applicator testing, however, gel was estimated to have been used in only 42.1% of sex acts, on average (41.1% Carraguard, 43.1% placebo). 1420 (23%) women in the intention-to-treat population had adverse events (713 Carraguard, 707 placebo), and 95 (2%) women had adverse events that were related to gel use (48 Carraguard, 47 placebo). Serious adverse events occurred in 72 (2%) women in the Carraguard group and 78 (3%) in the placebo group, only one of which was considered possibly related to gel use (placebo group).\n This study did not show Carraguard's efficacy in prevention of vaginal transmission of HIV. No safety concerns were recorded.", "The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.\n This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1 ratio 1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use.\n SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY.", "Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed.\n We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site.\n A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08).\n Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.)\n 2008 Massachusetts Medical Society" ]

[ "17051490", "16525097", "12693587", "11414432", "15838784", "16354821", "9185262", "11706666", "19769536" ]

[ "Azithromycin combination therapy with artesunate or quinine for the treatment of uncomplicated Plasmodium falciparum malaria in adults: a randomized, phase 2 clinical trial in Thailand.", "Effective treatment of uncomplicated Plasmodium falciparum malaria with azithromycin-quinine combinations: a randomized, dose-ranging study.", "A comparative clinical trial of combinations of dihydroartemisinin plus azithromycin and dihydroartemisinin plus mefloquine for treatment of multidrug resistant falciparum malaria.", "A randomized clinical trial of combinations of artesunate and azithromycin for treatment of uncomplicated Plasmodium falciparum malaria in Thailand.", "A multicenter study of azithromycin, alone and in combination with chloroquine, for the treatment of acute uncomplicated Plasmodium falciparum malaria in India.", "A double-blind, randomized study of azithromycin compared to chloroquine for the treatment of Plasmodium vivax malaria in India.", "Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria.", "Therapeutic responses to antibacterial drugs in vivax malaria.", "Azithromycin plus artesunate versus artemether-lumefantrine for treatment of uncomplicated malaria in Tanzanian children: a randomized, controlled trial." ]

[ "Because antimalarial drug resistance is spreading, there is an urgent need for new combination treatments for malaria, which kills >1 million people every year. Azithromycin is a macrolide antibiotic that is particularly attractive as an antimalarial because of its safety in children and the extensive experience with its use during pregnancy.\n We undertook a randomized, controlled, 28-day inpatient trial involving patients with acute, uncomplicated Plasmodium falciparum malaria. We compared the safety and efficacy of 2 azithromycin-artesunate combinations and 2 azithromycin-quinine regimens in adults with malaria. Treatments were as follows: cohort 1 received 3 days of azithromycin (750 mg twice daily) plus artesunate (100 mg twice daily), cohort 2 received 3 days of azithromycin (1000 mg once daily) plus artesunate (200 mg once daily), cohort 3 received 3 days of azithromycin (750 mg twice daily) plus quinine (10 mg/kg twice daily), and cohort 4 received 3 days of azithromycin (500 mg 3 times daily) plus quinine (10 mg/kg 3 times daily). The enrollment target was 25 evaluable subjects per group.\n The 28-day cure rates were similarly high in the artesunate and the standard-dose quinine cohorts: 92.0% (95% confidence interval [CI], 74.0%-99.0%), 88.9% (95% CI, 70.8%-97.6%), and 92.0% (95% CI, 74.0%-99.0%), for cohorts 1, 2, and 4, respectively. Late R1 treatment failures were seen in each of the artesunate and the standard-dose quinine cohorts. The cure rate for cohort 3 was 73.3% (95% CI, 44.9%-92.2%). In this cohort, 3 early treatment failures led to the termination of enrollment after 16 subjects had been enrolled. With mean parasite and fever clearance times (+/-SD) of 34+/-13 h and 20+/-20 h, the artesunate combinations were found to have led to a significantly (P<.001) faster clinical and parasitological improvement than occurred in the quinine cohorts (74+/-32 h and 43+/-37 h, respectively). Treatment-related adverse events were significantly more common in the quinine cohorts (P<.001). No deaths or drug-related serious adverse events were observed. In vitro results suggest that the treatment failures--particularly in the low-dose quinine cohort--were associated with decreased susceptibility to quinine, as well as with mefloquine cross-resistance.\n These data suggest that azithromycin-artesunate, even when given only once daily for 3 days, and azithromycin-quinine, given 3 times daily, are safe and efficacious combination treatments for uncomplicated falciparum malaria, and they deserve additional study in special patient populations.", "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.", "With the deteriorating situation of multidrug resistant falciparum malaria, a new drug or drugs in combinations are urgently needed. We conducted a study comparing a combination of dihydroartemisinin 240 mg and mefloquine 1,250 mg given over 3 days (Group 1) and a combination of dihydroartemisinin 240 mg and azithromycin 1,500 mg given over 3 days (Group 2), to determine safety, efficacy and tolerability. All of the patients stayed in a non-malaria endemic area during the study. By the third day after drug administration, most patients were free of parasites and none had serious adverse events. The cure rates at day 28 were 100% and 69.7% in Group 1 and Group 2, respectively (p<0.01). We conclude that a combination of dihydroartemisnin and azithromycin was safe and effective and may be another interesting regimen of the treatment of uncomplicated multidrug resistant Plasmodium falciparum malaria in Thailand.", "Recently, a combination of artesunate and mefloquine has proved effective, although is contraindicated in early pregnancy and young children. Azithromycin, a widely used antibiotic and has antimalarial effects, replace mefloquine as a new alternative antimalarial regimen. Two hundred and two uncomplicated falciparum malaria patients were randomly assigned to 1 of 3 regimens. Patients in group I (n = 68) received artesunate 200 mg once daily for 3 days, group II (n = 67) received artesunate 200 mg together with mefloquine 10 mg/kg on the first 2 days and artesunate 200 mg together with mefloquine 5 mg/kg on the third day, and group III (n = 67) received artesunate 200 mg together with azithromycin 50 mg once daily for 3 days. The 28 day cure rates were 44, 98 and 56%, respectively. The median time to recrudescence was significantly longer in group III. In conclusion, a combination of artesunate and azithromycin might be useful in treating children in whom bacterial and malarial infections may be concomitant. However, further work is required in order to enhance its clinical efficacy.", "Azithromycin has demonstrated in vitro and in vivo activity against Plasmodium falciparum, but small treatment studies have given mixed results.\n Participants with fever and with both a blood smear and a rapid diagnostic test positive for falciparum malaria were randomly assigned to groups that were treated with either azithromycin or chloroquine or to matched groups receiving a placebo. After an interim analysis, open-label combination therapy with both drugs was initiated.\n At day 28, 5 (33%) of 15 participants in the azithromycin-treated group had remained free of fever, compared with 4 (27%) of 15 in the chloroquine-treated group. All subsequently enrolled participants then received combination therapy with azithromycin and chloroquine. In 61 (97%) of 67 participants, resolution of fever and parasitemia had occurred by day 7, and, through day 28, no clinical or parasitologic relapse had occurred in them.\n Resolution of parasitemia was inadequate with monotherapy with either azithromycin or chloroquine, but combination therapy provided substantially improved clinical and parasitologic outcomes. The combination of azithromycin and chloroquine may be an effective alternative treatment for falciparum malaria and deserves further study.", "Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.", "The efficacy of the combination of artemether with doxycycline or azithromycin was evaluated in 60 patients with acute uncomplicated falciparum malaria who attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border). Patients (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg doxycycline as initial doses, followed by 100 mg artemether plus 100 mg doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another 4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by 250 mg azithromycin at 24 and 48 hours. The follow-up period was 28 days. Patients in either group had a rapid initial response to treatment with comparable PCT and FCT. The cure rate of artemether-azithromycin regimen was significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%). Low cure rate from artemether-azithromycin combination in this study was likely to be due to inadequate azithromycin dosage. However, with the low incidence of gastrointestinal adverse effects, the once daily dose of azithromycin could still be increased in order to enhance its clinical efficacy. The simplicity of drug administration and lesser incidence of adverse effects make azithromycin a more proper partner of artemether than doxycycline. Further dose-finding and pharmacokinetic study with the artemether-azithromycin combination is encouraging.", "Some antibacterial drugs have antimalarial activity that can be exploited for the prevention or treatment of malaria. Monotherapy with tetracycline, doxycycline, clindamycin or azithromycin was assessed in 1995-98 in 92 adult patients in Thailand with Plasmodium vivax malaria. All patients recovered following treatment and the early therapeutic responses were similar among the 4 groups. The overall median fever clearance time was 57 h and the mean (SD) overall time to parasite clearance was 134 (48) h. Of 66 patients who completed a 28-day follow-up, reappearances of vivax infection occurred in 27 patients (41%) from all groups; delayed appearances of falciparum malaria occurred in 6 patients (9%), only from the azithromycin group. The overall mean (SD) time to reappearance of P. vivax was 23 (5) days and time taken for detection of falciparum malaria was 13 (4) days after starting treatment for vivax malaria. The 28-day cumulative cure rates of clindamycin (n = 12), tetracycline (n = 18) and doxycycline (n = 18) groups were similar (P > or = 0.14) and all were significantly higher compared to the azithromycin group (n = 18; P < or = 0.04). The intervals until vivax reappearance were also significantly shorter in the azithromycin group [mean (SD) = 21 (6) vs 25 (3) days, P < 0.05] suggesting that some of these were recrudescences. The apparent success rate (no subsequent appearances of either vivax or falciparum infection) was significantly lower for the azithromycin group (11%) compared to the other groups (34-78%; P < 0.01). In current antibacterial treatment regimens, short-course azithromycin has inferior antimalarial activity compared to clindamycin or the tetracyclines.", "Acute febrile illness is the most common cause of outpatient attendance and mortality for children in Africa. Malaria and bacterial disease are difficult to differentiate with limited diagnostic facilities. Combinations of antibiotics and antimalarials are potentially attractive for treatment of the syndrome. Azithromycin plus artesunate (AT+AS) is an effective antimalarial combination for adults in Asia.\n We performed an individually randomized, open-label trial of AZ+AS versus artemether-lumefantrine (AL) involving children (age, 6-59 months) with uncomplicated malaria in Muheza, Tanzania. The primary outcome was parasitological failure by day 28. Parasitological failure by day 42 and failure corrected for reinfection were major secondary outcomes.\n Of 2497 children screened, 261 were eligible; 129 were randomized to the AZ+AS arm, and 132 were randomized to the AL arm; 92% and 91%, respectively, underwent follow-up to 28 days. Planned interim analysis was performed after 200 patients reached day 28 follow-up and led the Data and Safety Monitoring Board to halt further recruitment. All children had a complete initial response to treatment, but 69 (58%) of 119 children in the AZ+AS arm and 24 (20%) of 120 in the AL arm had asexual parasites at or by day 28 (adjusted odds ratio for failure with AZ+AS treatment, 6.1; 95% confidence interval, 3.3-11.4; P < .001). When analysis was restricted to children with recrudescence, the parasitological failure rate was 32% in the AZ+AS arm and 9% in the AL arm. This difference was maintained at day 42.\n This trial does not support the use of AZ+AS as treatment for malaria or acute febrile illness in children in areas of Africa with high levels of existing antimalarial drug resistance.\n ClinicalTrials.gov NCT00694694." ]

[ "938184", "6151246", "4342116" ]

[ "Schizophrenia--a follow-up study of results of treatment. I. Design and other problems.", "Effects of psychotherapy in schizophrenia: II. Comparative outcome of two forms of treatment.", "Group vs individual psychotherapy with schizophrenics. A controlled outcome study." ]

[ "This is the first of a series of articles on a follow-up study of the results of treatment of schizophrenia, studied over a period of two to five years after first admission and first release. The study compares the follow-up outcome of five different treatment methods given to first-admission male and female schizophrenic patients in the hospital. The design of the study is used as a basis for description and discussion of the practical, ethical, and statistical problems involved. A distinction is made between follow-up and continued treatment design, and it is concluded that both pose massive problems in execution, analysis, presentation, and interpretation.", "This study compares the effects of exploratory, insight-oriented (EIO) and reality-adaptive, supportive (RAS) forms of psychotherapy on a sample of 95 schizophrenic patients. Analyses of 2-year outcomes revealed a complex interaction between the type of psychotherapy provided and the domain of psychopathology affected. RAS psychotherapy exerted clear preferential effects in the areas of recidivism and role performance. The EIO psychotherapy exerted preferential, albeit more modest, action in the areas of ego functioning and cognition. Overall, however, the magnitude of the differences was low. The results highlighted the need for more focused studies of subgroups, and of process and contextual influences on outcome.", "nan" ]

[ "21748313", "20063224", "7657008", "22717414", "19217592", "11120525", "16542657" ]

[ "A randomized controlled trial to study the effect of IV hydration on the duration of labor in nulliparous women.", "A randomized trial of increased intravenous hydration in labor when oral fluid is unrestricted.", "Hyponatraemia and non-electrolyte solutions in labouring primigravida.", "Increased intravenous hydration of nulliparas in labor.", "A randomized, double-blinded, controlled trial comparing parenteral normal saline with and without dextrose on the course of labor in nulliparas.", "A randomized controlled trial of the effect of increased intravenous hydration on the course of labor in nulliparous women.", "Increased intravenous fluid intake and the course of labor in nulliparous women." ]

[ "To compare the effects of two different regimens of intravenous hydration and oral hydration on the duration of active labor.\n Two hundred and ninety-three low risk term primigravida in active labor were randomized into three groups. The first group had 99 patients who received oral fluids only, the second group of 98 patients received intravenous Ringer lactate at the rate of 125 ml/h (IV 125 ml) and the third group had 96 patients who received intravenous Ringer lactate at a rate of 250 ml/h (IV 250 ml). Amniotomy and oxytocin administration were allowed according to the physician's discretion.\n The mean duration of labor in the oral fluid group was 391, 363 min in the 125 ml/h group and 343 min in the 250 ml/h group, P = 0.203. The incidence of prolonged labor more than 12 h in the oral fluid group was 7.1% in the oral fluid group, 4.1% in the 125 ml/h group and 3.1% in the 250 ml/h group, P = 0.402. The oxytocin requirement was 37% in the oral group, 32% in the 125 ml/h group and 33% in the 250 ml/h group, P = 0.68. There was a statistically significant reduction in the incidence of vomiting in patients receiving intravenous hydration, i.e. 24.2% in the oral group, 11.2% in the 125 ml/h group and 6.3% in the 250 ml/h group, P = 0.001. There was no difference in the mode of delivery, maternal or neonatal complications between the three groups.\n This study establishes a trend towards decreased incidence of prolonged labor and less vomiting in patients receiving intravenous hydration.", "Increased intravenous (IV) hydration is associated with decreased labor duration and oxytocin augmentation in nulliparous women when oral fluid is restricted. The objective of this study was to determine the effect of increased IV hydration on the duration of labor when access to oral fluid was unrestricted.\n Term, nulliparous women with uncomplicated singleton pregnancies were randomly assigned to receive lactated ringers at 250 ml per hour (IV fluid group) throughout active labor or usual care. All women were allowed unrestricted access to oral fluids.\n Eighty women completed the study, 37 in the IV fluid group and 43 in the usual care group. There was no difference in the primary outcome of total duration of labor (9.5 versus 9.4 hours) or in the secondary outcomes of duration of the first stage (7.9 versus 8.0 hours), duration of second stage (1.6 versus 1.4 hours), or rate of oxytocin augmentation (51% versus 44%).\n Increased IV hydration does not decrease labor duration in nulliparous women when access to oral fluid is unrestricted.", "We performed a prospective randomised study on one hundred primigravid women who required oxytocin to augment labour, comparing dextrose infusion with normal saline. After delivery, the 45 patients whose oxytocin was infused in dextrose had significantly lower serum sodium levels in both mother and baby compared to the 48 patients who had their oxytocin administered in normal saline. This was particularly evident in those cases where epidural analgesia was employed.", "To assess the effects of intravenous hydration on the duration of active labor in nulliparous women also allowed unrestricted oral consumption of fluids.\n In a randomized clinical trial 120 nulliparous women with uncomplicated singleton pregnancies at term were randomly assigned to drink fluids at will and receive either no intravenous hydration (group 1) or a Ringer lactate solution at rates of 60 mL, 120 mL, or 240 mL per hour (groups 2-4) throughout active labor.\n There were differences in duration for the active phase of the first stage of labor (252.3 ± 40.9 min in group 1 vs 206.7±38.3 min in group 4; P<0.001) and for the second stage (64.3 ± 13.9 in group 1 vs 49.8 ± 11.4 min in group 4; P=0.01), but not for the third stage. The percentage of participants who needed labor augmentation with oxytocin was less when intravenous hydration was provided (53.3% in group 1 vs 20.0% in group 4; P=0.02).\n Intravenous hydration significantly decreased the duration of active labor and reduced the frequency of both prolonged labor and oxytocin administration in nulliparous women. htpp://www.irct.ir registration number: IRCT201105256575N2.\n Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "The objective of the study was to compare intravenous normal saline with and without dextrose on the course of labor in nulliparae.\n In a double-blinded, controlled trial, term, nulliparae with singletons in active labor were randomized into 1 of 3 groups receiving either normal saline (NS), NS with 5% dextrose (D5NS), or NS with 10% dextrose (D10NS) at 125 mL/h. The primary outcome was total length of labor from onset of study fluid in vaginally delivered subjects. Maternal and neonatal outcomes were also analyzed.\n Of 300 subjects enrolled, 289 met inclusion criteria and completed the study. In vaginally delivered subjects, significant differences were noted in the second stage (P = .01) and total length of labor (P = .02). No significant differences were observed in the cesarean section rates between the groups (P = .21). No differences were noted in maternal or neonatal secondary outcomes.\n Administration of a dextrose solution, regardless of concentration, was associated with a shortened labor course in term vaginally delivered nulliparae subjects in active labor.", "One variable that has the potential to affect the course of labor but has not been evaluated previously is the adequacy of maternal hydration. Typical orders provide for 125 mL of intravenous fluids per hour in patients taking limited oral fluids. Many such patients are clinically dehydrated. Physiologists have shown that increased fluids improve skeletal muscle performance in prolonged exercise. This study was designed to determine whether increased intravenous fluids affect the progress of labor.\n Nulliparous women with uncomplicated singleton gestations at term, in spontaneous active labor with dilatation between 2 and 5 cm, and with a cephalic presentation were included. Patients who gave consent were randomly selected to receive either 125 mL or 250 mL of intravenous fluids per hour.\n One hundred ninety-five patients were randomly selected, 94 to the 125-mL group and 101 to the 250-mL group. Prerandomization variables were well matched between the 2 groups. The mean volume of total intravenous fluids was significantly greater in the 250-mL group (2008 mL vs 2487 mL; P =.002), as was the mean hourly rate (152 mL/h in the 125-mL group vs 254 mL/h in the 250-mL group; P =.001). The frequency of labor lasting >12 hours was statistically higher in the 125-mL group (20/78 [26%] vs 12/91 [13%]; P =.047). In addition, there was a trend favoring longer mean duration of the first stage and total duration of labor in patients delivered vaginally in the 125-mL group, by 70 and 68 minutes, respectively (P =.06). There was a trend toward a lower frequency of oxytocin administration for inadequate labor progress in the higher fluid rate group (61 [65%] in the 125-mL group vs 51 [49%] in the 250-mL group; P =.06). Cesarean deliveries were more frequent in the 125-mL group (n = 16) than in the 250-mL group (n = 10) but did not reach statistical significance.\n This study presents the novel finding that increasing fluid administration for nulliparous women in labor above rates commonly used is associated with a lower frequency of prolonged labor and possibly less need for oxytocin. Thus inadequate hydration in labor may be a factor contributing to dysfunctional labor and possibly cesarean delivery. Consideration of this factor in clinical management and in future studies considering variables that affect labor is warranted.", "To compare the effect of 2 regimens of intravenous fluid therapy on the course of labor.\n In a prospective, randomized, double-blind study of 300 nulliparous pregnant women at term conducted at a teaching hospital, 153 women received 125 mL and 147 received 250 mL of intravenous fluid per hour. The groups were matched and analysis was done using the t, chi(2), and Fisher exact tests. P<0.05 was considered statistically significant.\n In the group that received intravenous fluid at a rate of 250 mL per hour the mean+/-S.D. duration of labor was significantly shorter (253+/-97 vs. 386+/-110 min; P = 0.0001), the frequency of labor lasting both more than 10h and more than 15 h was statistically lower (4.8% vs. 13.8%; P=0.001 and 0% vs. 4.5%; P=0.02, respectively), and the frequency of oxytocin administration was significantly lower (8.1% vs. 20.4%; P=0.001). There was a trend toward a lower frequency of cesarean deliveries in the 250-mL group (16% vs. 22.8%; P=0.1).\n A greater volume per hour of intravenous fluid than is commonly administered to nulliparous women in active labor is associated with significantly shorter duration of labor and lower frequency of both prolonged labor and oxytocin administration." ]

[ "6137255", "2274638", "6135468", "71397", "8909331", "16497273", "7030444", "1347291", "1676029" ]

[ "Propranolol in schizophrenia: a double blind, placebo controlled trial of propranolol as an adjunct to neuroleptic medication.", "A double-blind, placebo-controlled study of adjunctive nadolol in the management of violent psychiatric patients.", "Oxprenolol in schizophrenic patients with tardive dyskinesia: a double-blind placebo-controlled, crossover study.", "Propranolol as an adjunct to the treatment of schizophrenia.", "Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients.", "Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial.", "A trial of propranolol in chronic schizophrenia.", "Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study.", "A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia." ]

[ "A double blind, placebo controlled trial was carried out to examine the contribution of propranolol as an adjunct to neuroleptic medication in the treatment of chronic schizophrenic patients whose florid symptoms had not remitted with neuroleptic medication alone. Propranolol was shown to have a more beneficial effect than placebo, but the results were much less dramatic than those which have been described in previous studies. Recent work has shown that there may be a pharmacokinetic interaction between propranolol and neuroleptics, and this should be considered as one possible explanation of our findings.", "We report a controlled 3-week study (n = 30) of adjunctive use of nadolol, 80 to 120 mg per day, vs. placebo for the management of violent psychiatric patients. There were no remarkable adverse cardiac effects at this dose. The active treatment group showed lower total Brief Psychiatric Rating Scale (BPRS) scores after the first week of treatment (analysis of covariance [ANCOVA], p less than .08) and similar trends for the activation factor and the hostility scale. There were parallel findings for measures of extrapyramidal symptoms (EPS) (Simpson-Angus Neurological Rating Scale), which were reliable after the second week (ANCOVA, p less than .02). A significant association between changes in EPS and BPRS scores was found by regression analysis, after the effects of baseline measures were removed. Given that nadolol does not penetrate the central nervous system well, the antiaggressive effects may be associated with sympathetic nervous system feedback mechanisms.", "Tardive dyskinesia is a syndrome of involuntary movements that develops during or following long-term neuroleptic treatment. Current treatment of tardive dyskinesia is unsatisfactory. Neuroleptics can reduce the syndrome, but the underlying pathogenetic process is probably aggravated during treatment. The use of these drugs is necessary, however, when the patient simultaneously exhibits intense psychotic and dyskinetic symptoms. In this controlled study, 8 patients were treated with a beta-blocker drug, oxprenolol, as a slow-release preparation that was administered in increasing doses up to 640 mg per day for one month. We conclude that this drug can ameliorate both the psychotic features of schizophrenics and their tardive dyskinetic movements without producing significant side-effects.", "Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more.", "This study assessed the safety and efficacy of nadolol 120 mg/day compared with placebo, when administered adjunctively to neuroleptic in a group of acutely aggressive schizophrenic patients.\n Thirty-four male patients enrolled in this double-blind, placebo-controlled trial. The subjects were evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Simpson Angus Neurologic Rating Scale for extrapyramidal effects. The total BPRS score as well as three factors, thought disturbance, hostility, and activation, was analyzed.\n Compared with those who received placebo, the patients taking nadolol showed significant improvement on total BPRS score, particularly on the thought disturbance and activation factors, after the first treatment week (p = .05). By the end of the second treatment week, the patients taking placebo also began to show improvement, and the group differences were no longer significant. The patients treated with nadolol showed significantly more improvement on Simpson-Angus scores than those who received placebo (p = .03). However, there was no significant correlation between BPRS and Simpson-Angus changes. In the nadolol group, patients with and without akathisia showed no significant difference in their BPRS scores.\n These findings suggest that adjunctive nadolol may be useful in the treatment of acutely aggressive schizophrenic patients by inducing a more rapid and consistent decrease of overall psychiatric symptoms and by reducing the extrapyramidal effects. Our results raise the possibility that the mechanism of action of nadolol on psychiatric symptoms in schizophrenic patients may be different from the mechanism of improvement of neuroleptic-induced extrapyramidal symptoms and akathisia. Nadolol may be a helpful adjunctive treatment for schizophrenic patients in general and not just for those with a high hostility level.", "Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism.\n In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of > or = 2 points on BAS). Analysis was by intention to treat.\n Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS: -34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p = .0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia.\n The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices.", "nan", "Considerable evidence indicates that the lipophilic beta-blocker propranolol is useful in treating organically based aggression. This study looked at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression in chronic psychiatric inpatients.\n Forty-one chronic psychiatric inpatients with an average of one aggressive outburst per week (defined by the Overt Aggression Scale [OAS]) were entered into a double-blind, placebo-controlled study lasting 17 weeks. The OAS was used to track aggression on a per-incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions scale (CGI) were used to track clinical status.\n Nadolol subjects showed a significant decline in frequency of aggression compared with controls (p = .026) and a significant decline in the BPRS total score (p = .007) and in the subfactors \"hostility and suspicion,\" \"negative symptoms,\" and \"signs of hyperarousal/tension.\" There was no significant change in CGI \"severity of illness\" ratings between groups, although the nadolol group was significantly improved from baseline at every subsequent time period while the placebo group was unchanged throughout the study.\n Nadolol is of significant benefit in the treatment of aggression in chronic psychiatric inpatients. This drug does penetrate the brain over time, but the success of a drug whose primary locus of action is peripheral may implicate a bimodal mechanism of action, i.e., a role for the CNS and the soma in the maintenance of aggression.", "Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory.\n To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale.\n No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders.\n The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition." ]

[ "16831672", "18647310", "18230389", "10200704", "15857105", "8426717", "18093246", "16403107", "12140475", "2195345", "19141065", "15149513", "17438179", "18158199", "16150205" ]

[ "A randomized controlled trial to compare steroid with cyclosporine for the topical treatment of oral lichen planus.", "Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study.", "A comparative treatment study of topical tacrolimus and clobetasol in oral lichen planus.", "Efficacy of topical mesalazine compared with clobetasol propionate in treatment of symptomatic oral lichen planus.", "The effectiveness of 1% pimecrolimus cream in the treatment of oral erosive lichen planus.", "Fluocinonide in an adhesive base for treatment of oral lichen planus. A double-blind, placebo-controlled clinical study.", "The efficacy of aloe vera gel in the treatment of oral lichen planus: a randomized controlled trial.", "Ciclosporin vs. clobetasol in the topical management of atrophic and erosive oral lichen planus: a double-blind, randomized controlled trial.", "Fluticasone propionate spray and betamethasone sodium phosphate mouthrinse: a randomized crossover study for the treatment of symptomatic oral lichen planus.", "Effect of topical cyclosporine rinse on oral lichen planus. A double-blind analysis.", "Topical clobetasol in the treatment of atrophic-erosive oral lichen planus: a randomized controlled trial to compare two preparations with different concentrations.", "A new delivery system of clobetasol-17-propionate (lipid-loaded microspheres 0.025%) compared with a conventional formulation (lipophilic ointment in a hydrophilic phase 0.025%) in topical treatment of atrophic/erosive oral lichen planus. A Phase IV, randomized, observer-blinded, parallel group clinical trial.", "Treatment of oral erosive lichen planus with 1% pimecrolimus cream: a double-blind, randomized, prospective trial with measurement of pimecrolimus levels in the blood.", "Betamethasone oral mini-pulse therapy compared with topical triamcinolone acetonide (0.1%) paste in oral lichen planus: A randomized comparative study.", "Comparative observation on the effects of Radix tripterygium hypoglaucum tablet and Tripterygium glycosides tablet in treating erosive oral lichen planus." ]

[ "To compare the effectiveness of cyclosporine solution versus triamcinolone acetonide in orabase in the treatment of oral lichen planus (OLP) in reducing signs and symptoms.\n One hundred thirty-nine biopsy-proven OLP patients were randomly assigned to cyclosporine (68) or steroid (71) applied onto the target lesion and affected areas. Assessments were at weeks 0, 2, 4, 8 by clinical scoring and grid measurement of the target lesion (reticulation, erythema, ulceration). Patients ranked severity of pain and burning sensation using visual analog scales.\n Although clinical response, pain, burning sensation, area of reticulation, erythema, and ulceration at week 4 were all worse in patients receiving cyclosporine than in those receiving steroid, the differences were not statistically significant. Large patient-to-patient variability was evident over the observation period, with little evidence of marked changes in levels over time in both treatment groups.\n Topical cyclosporine appears no more effective than steroid in the treatment of oral lichen planus.", "Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option.\n To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP.\n Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts.\n Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1).\n Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.", "Existing clinical trials have shown that topical corticosteroids are often effective in the management of oral lichen planus (OLP). However, tacrolimus has recently been shown to be an effective treatment of OLP.\n To compare the effectiveness of clobetasol and tacrolimus in the topical management of OLP.\n In this randomized comparative double-blind study, 30 consecutive patients with oral lesions consistent clinically and histologically with OLP were recruited. The patients were divided into 2 groups to receive clobetasol 0.05% or tacrolimus 0.1% ointment and were treated for 6 weeks.\n The profiles of mean lesion sizes and mean pain measures did not differ between the tacrolimus and clobetasol treatment groups.\n We found tacrolimus to be as useful as clobetasol in treatment of OLP. We believe that up-to-date evidence indicates the effectiveness of tacrolimus in treating OLP.", "To compare topically applied mesalazine (5-aminosalicylic acid) to topically applied clobetasol propionate in the treatment of patients suffering from symptomatic oral lichen planus.\n Randomized controlled longitudinal investigation.\n Twenty-five out-patients suffering from oral lichen planus and referred to the Department of Oral Pathology and Oral Medicine of the University of Milan, Italy, during the period January to August 1997. Patients were randomly allocated (Group A and Group B) to treatment with mesalazine 5% or clobetasol propionate 0.05%. The drugs were topically applied twice daily for 4 weeks. Discomfort and pain were evaluated by the patient before and after treatment using a Visual Analogue Scale from zero (no pain) to 10 (extreme pain). Results were statistically evaluated by a Mann-Whitney U test.\n The two pharmacological regimens obtained partial and complete absence of symptoms. In particular, the mesalazine tested group disclosed 57% complete absence of symptoms, 21.3% partial response and 9% no response. No statistically relevant difference has been detected between the two regimens.\n The results of this preliminary study, if confirmed by further investigations, suggest that mesalazine might be considered an alternative to clobetasol propionate for treatment of symptomatic oral lichen planus.", "The purpose of this study was to evaluate the efficacy, relative safety, and tolerability of 1% pimecrolimus cream in the treatment of oral erosive lichen planus (OELP).\n Twenty patients with OELP were randomized into equal groups; group 1 applied 1% pimecrolimus cream twice daily to their oral lesions for 4 weeks, whereas group 2 applied a placebo cream. Photographs of the lesions were taken and analyzed for areas of ulceration, erythema, and reticulation. Discomfort scores were also assessed with a visual analogue scale (VAS). Blood samples were taken at baseline and at study completion; a complete blood count with differential and comprehensive metabolic panel was ordered. The Wilcoxon signed rank test was used.\n The experimental group showed a decrease in ulceration (alpha = 0.068) and erythema (alpha = 0.005) at the mid-point with continued reduction of erythema at the final (alpha = 0.075) time measurement. The control group demonstrated an increase in reticulation at the mid-point (alpha = 0.017) and final (alpha = 0.007) time measurement. The VAS scores for the experimental group decreased during the study (alpha = 0.022). Blood levels were within the normal range.\n The OELP lesion size in the 1% pimecrolimus group decreased and the pimecrolimus cream was found to significantly reduce the patient's pain scores. Further study of 1% pimecrolimus as therapy for OELP is warranted since it was shown to be effective, relatively safe, and well tolerated by patients within the limits of this short-term study.", "Patients with symptomatic oral lichen planus frequently require therapy to reduce signs and symptoms. For this purpose, corticosteroids are often applied topically. In a randomized, double-blind, placebo-controlled study, the efficacy of the topical application of 0.025% fluocinonide was evaluated. Forty consecutive patients with oral lichen planus diagnosed on the basis of histopathologic and immunofluorescence findings participated in this study. All patients were followed for 3 to 17 months. No adverse effects were noted during follow-up period. In the group of 20 patients that received the drug, 4 patients (20%) showed a complete remission, and 12 patients (60%) had a good or partial response to topical treatment. In the placebo-group, these figures were 0 and 6 (30%), respectively. The majority of the placebo-group (70%) did not respond at all with regard to signs (Xt2 = 10.4; p = 0.0013) and symptoms (Xt2 = 6.97, p = 0.008). The results from this study suggest that topical application of fluocinonide in an adhesive base is a safe and effective drug to reduce signs and symptoms in oral lichen planus.", "Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful especially in the atrophic and erosive forms. Several therapies have been tried, with varying results. There is one case report in which aloe vera (AV) was used successfully in the treatment of lichen planus.\n To compare the efficacy of AV and placebo in the topical management of OLP.\n A randomized, double-blind, placebo-controlled trial was designed. Fifty-four patients were randomized into two groups to receive AV gel or placebo for 8 weeks.\n Fifty-four consecutive patients (34 women and 20 men) participated in the study. We found erosive and ulcerative lesions in 83% and 17%, respectively. The most common site of OLP was the lower lip. Twenty-two of 27 patients treated with AV (81%) had a good response after 8 weeks of treatment, while one of 27 placebo-treated patients (4%) had a similar response (P<0.001). Furthermore, two patients treated with AV (7%) had a complete clinical remission. Burning pain completely disappeared in nine patients treated with AV (33%) and in one treated with placebo (4%) (P=0.005). Symptomatology improved by at least 50% (good response) in 17 patients treated with AV (63%) and in two treated with placebo (7%) (P<0.001). No serious side-effects were found in both groups.\n AV gel is statistically significantly more effective than placebo in inducing clinical and symptomatological improvement of OLP. Therefore, AV gel can be considered a safe alternative treatment for patients with OLP.", "Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, especially in the atrophic and erosive forms. Several drugs have been used with varying results, but most treatments are empirical, and do not have adequate control groups or correct study designs.\n To compare the effectiveness of clobetasol and ciclosporin in the topical management of OLP and to evaluate which is more cost-effective and which gives the longest remission from signs and symptoms.\n A randomized, comparative, double-blind study was designed. Forty consecutive patients were divided into two groups to receive clobetasol propionate or ciclosporin for 2 months. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Antimycotic prophylaxis was also given. After the end of therapy, patients underwent a 2-month follow-up.\n Eighteen of 19 clobetasol-treated patients (95%) improved after 2 months of therapy, while 13 of 20 ciclosporin-treated patients (65%) had a clinical response (P = 0.04). Symptomatology improved in 18 clobetasol-treated patients (95%) and in 17 ciclosporin-treated patients (85%) (not statistically significantly different). Two months after the end of therapy, 33% of clobetasol-treated patients and 77% of ciclosporin-treated patients were stable (P = 0.04). Clobetasol produced significantly more side-effects than ciclosporin (P = 0.04). The daily cost of ciclosporin treatment was 1.82 compared with 0.35 for clobetasol therapy.\n Clobetasol is more effective than ciclosporin in inducing clinical improvement, but the two drugs have comparable effects on symptoms. Conversely, clobetasol gives less stable results than ciclosporin when therapy ends and has shown a higher incidence of side-effects. The daily cost of ciclosporin is more than five times higher than clobetasol.", "Symptomatic oral lichen planus (OLP) has been palliated with a wide spectrum of topical and systemic therapies. Although the majority of management strategies include corticosteroids, few have been evaluated in randomized controlled trials.\n We investigated the acceptability and efficacy of topical fluticasone propionate spray (FP) and betamethasone sodium phosphate mouthrinse (BSP) upon the signs and symptoms of OLP, assessing patient quality of life changes as a consequence of these therapies.\n We implemented a randomized, crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London, United Kingdom. We treated 48 patients with biopsy-proven symptomatic OLP, and 44 patients (92%) completed the study. The dosage was 50 microg two dose unit sprays and BSP 500 microg, each 4 times daily. Symptomatic improvement was evaluated by means of a visual analogue scale (VAS), the McGill pain score, the Oral Health Impact Profile (OHIP), and Oral Health Quality of Life (OHQoL) questionnaires. The total surface area of the lesions, including all white, erythematous, and ulcerative lesions was measured at each visit. The efficacy, ease of application, and adverse effects associated with each medication were recorded.\n Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices. There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms (measured by the VAS) or in their effect on patient quality of life. Both FP and BSP significantly reduced the surface area of oral lesions. However, FP was statistically significantly better than BSP in reducing lesion surface area. There was no statistically significant difference between the patient-assessed effects of the 2 therapies.\n FP and BSP are both effective in the short-term clinical management of symptomatic OLP. FP is more acceptable to patients than BSP because of the convenience of the spray form.", "Oral lichen planus is a relatively common disorder of the mouth that can be debilitating. It is frequently palliated with topical or systemic corticosteroids and retinoids. These treatments require prolonged use, however, and are not always effective.\n In a double-blind trial, 16 patients with symptomatic oral lichen planus were randomly assigned to receive either topical cyclosporine or its vehicle. The patients swished and expectorated 5 ml of medication (containing 100 mg of cyclosporine per milliliter) three times daily.\n After eight weeks, the eight recipients of cyclosporine had marked improvement in erythema (P = 0.003), erosion (P = 0.02), reticulation (presence of white lacelike lesions; P = 0.007), and pain (P = 0.002), whereas the eight recipients of vehicle had no change or minimal improvement. After a switch to cyclosporine for eight weeks, the vehicle-treated patients had improvement similar to that seen in the patients who initially received cyclosporine. There were no systemic side effects. In most cases blood cyclosporine levels were low or undertectable. Cyclosporine levels present in specimens of oral mucosa at the end of therapy four hours after the patients swished were similar to the levels previously reported in psoriatic lesions after treatment with systemic cyclosporine (14 mg per kilogram of body weight per day).\n As a topical preparation, cyclosporine may be useful in the treatment of oral lichen planus and possibly other cutaneous disorders.", "Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical and do not have adequate control groups or correct study designs. However, to date, the most commonly employed and useful agents for the treatment of LP are topical corticosteroids. A randomized, double-blind, placebo-controlled trial has been designed to compare the efficacy and safety of two different formulations of clobetasol, a very potent topical steroid, in the topical management of OLP and to evaluate which gives the longest remission from signs and symptoms. Thirty-five consecutive patients were divided into two groups: the first received clobetasol propionate 0.025% and the second was given clobetasol propionate 0.05%. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Anti-mycotic prophylaxis was also added. After the end of therapy, patients received a 2-month follow-up. In all, 14 of the 15 clobetasol 0.025% patients (93%) and 13 of the 15 clobetasol 0.05% patients (87%), had symptoms improvement after 2 months of therapy (P = 0.001 in both groups). Also, 13 of the 15 clobetasol 0.025% patients (87%) and 11 of the 15 clobetasol 0.05% patients (73%) had clinical improvement after 2 months of therapy (P < 0.05 in both groups). No statistical differences were found in comparing the two different formulations. A larger concentration of the active molecules cannot further improve the therapeutic findings or optimize the obtained results in a significant manner.", "Topical application of clobetasol-17-propionate has been diffusely reported as an efficacious therapy in atrophic/erosive oral lichen planus (OLP), without exposing the patient to systemic side-effects. However, prolonged contact and respective topical effects on the oral mucosa should be avoided.\n The aim of the present study was to evaluate efficacy and compliance of new lipid microspheres loaded with 0.025% of clobetasol propionate (formulation A) compared with a commonly used formulation (a sort of dispersion of a lipophilic ointment in a hydrophilic phase) with the same amount of drug (formulation B) in the topical treatment of OLP.\n Fifty patients with symptomatic OLP were enrolled in a controlled single-blind phase IV clinical trial. After a dropout of five patients, a total of 45 patients [12 males and 33 females; mean age 61.1 years (+/- 12.3 SD; range 25-82)] were treated (17 with formulation A and 28 with formulation B, matched for gender and age; P > 0.2) with the same dosage regimen. At times T0, T1 and T2 we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0-100); (ii) clinical score; (iii) clinical resolution; and (iv) patient compliance. Statistical analysis was calculated using S-Plus 4.0 and SPSS 9.0 (Student's t-test, chi(2), Kolmogorov-Smirnow, Friedman, Student-Newman-Keuls, Mann-Whitney U-test and Spearman tests).\n Both formulations were found to be similar for parameters ii, iii and iv, although with a better general trend for formulation A; a significant difference was registered for formulation A in terms of a reduction in painful symptoms (parameter i) at time T2 (P = 0.02).\n Our results suggest that the new topical drug delivery system (formulation A) may enhance, at least in terms of symptom remission and compliance, the effectiveness of clobetasol propionate at a dose of 0.025% in OLP therapy.", "To evaluate the efficacy of 1% pimecrolimus cream in treating oral erosive lichen planus and to assess its tolerance.\n Double-blind randomized trial with placebo control.\n Outpatients of the Department of Dermatology, University Hospital of Nice, from December 21, 2004, to April 19, 2005.\n Fourteen consecutive patients with oral erosive lichen planus confirmed by histological examination and with a clinical score superior to 3. Of the 14 patients, 2 did not meet the inclusion criteria and 12 were enrolled in the trial.\n The intervention was 1% pimecrolimus cream or its vehicle, which was applied on ulcerated lesions twice a day for 4 weeks.\n The efficacy of the treatment was quantified using a 12-point clinical score. The blood level of pimecrolimus was analyzed on days 0 (baseline), 14, and 28.\n In the placebo group, the mean score was 4.67 on day 0 vs 3.33 on day 28 (P = .22). In the pimecrolimus group, the mean score was 6.83 on day 0 vs 3.33 on day 28 (P = .04). In the pimecrolimus group, blood concentrations of pimecrolimus were always above the threshold (mean value, 2.84 ng/mL; extreme values, 0-6.19 ng/mL). Pimecrolimus cream was well tolerated, and only transient burning sensations were reported by some subjects. Each of the patients in the pimecrolimus group whose condition improved subsequently relapsed when assessed 1 month after treatment.\n The 1% pimecrolimus cream seems to be an effective and well-tolerated treatment for oral erosive lichen planus. The finding of systemic levels of pimecrolimus after mucosal applications necessitates long-term study because it seems that long-term application is required to maintain clinical improvement.", "Betamethasone oral mini-pulse (OMP) therapy has been used effectively and safely in vitiligo, alopecia areata, and lichen planus.\n We sought to evaluate the efficacy and safety of betamethasone OMP in patients with symptomatic moderate to severe oral lichen planus and to compare it with topical triamcinolone acetonide.\n In all, 49 patients with moderate to severe oral lichen planus were randomly allocated to receive either OMP comprising 5 mg of betamethasone orally on 2 consecutive days per week (group A) or triamcinolone acetonide (0.1%) paste application thrice daily (group B), for 3 months followed by stepwise tapering during the next 3 months. Treatment response was assessed by the change in the score, which was based on the number of sites involved and the area affected. The changes in the symptoms and side effects were also recorded. Patients were followed up after treatment for 3 months to look for relapse.\n In all, 23 of 25 patients in group A and 23 of 24 patients in group B completed the study. Good to excellent response was seen in 17 of 25 (68.0%) patients in group A as compared with 16 of 24 (66.0%) in group B at 6 months. Symptom-free state was achieved in 13 of 25 (52%) patients in group A and 12 of 24 (50%) in group B. The difference in the mean scores within each group was statistically significant from the fourth week onward in group A and eighth week onward in group B, whereas in patients with erosive disease it was second and twelfth week onward, respectively. The difference in the treatment response between the two groups was statistically significant only at week 24 when reduction in severity score was more in triamcinolone group. Side effects were seen in 14 (56%) patients in group A and 6 (25%) patients in group B, which were mild and reversible. Relapse occurred in 9 of 23 (39.1%) patients in group A after 13.78 +/- 6.96 weeks as compared with 5 of 23 (21.7%) in group B after 19.20 +/- 1.79 weeks.\n The study was not blinded and the change in the quality of life with treatment was not measured.\n Betamethasone OMP improves the clinical outcome in patients with moderate to severe oral lichen planus. When compared with topical triamcinolone acetonide it is equally effective but the response is earlier, especially in erosive disease. It may be a useful and convenient alternative either as a monotherapy or to achieve rapid symptomatic relief during periods of exacerbations.", "To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus (EOLP).\n The patients were randomized into two groups, and they were treated with THT (n = 47) or TGT (n = 47), respectively. The therapeutic effects were evaluated after 3 months treatment.\n For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P = 0.043). However, for the patients of grade 2, the difference was not statistically significant (P = 0.173).\n TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age." ]

[ "9150331" ]

[ "Home intravenous therapy in cystic fibrosis: a prospective randomized trial examining clinical, quality of life and cost aspects." ]

[ "In this study, we set out to determine if home intravenous (i.v.) antibiotic therapy in adult patients with cystic fibrosis (CF) is a feasible, effective and less costly alternative to hospitalization, and to assess the impact of home therapy on quality of life. The study was a prospective, randomized, two-factor mixed design involving adults presenting with respiratory exacerbations of CF. Patients were randomized such that they were discharged home after 2-4 days, or remained in hospital. Seventeen patients had 31 admissions (13 home and 18 hospital). Following 10 days of therapy, there were no significant differences between home or hospital arms with respect to body weight, 12 minute walking distance, sputum weight, pulse oximetry, or improvement in lung function (forced expiratory volume in one second (FEV1), or forced vital capacity (FVC)). Patients who remained in hospital were less fatigued and noted a greater degree of mastery. Patients discharged early noted less disruption to their family life, personal life and sleeping pattern. The total cost for the home therapy arm was approximately half that of the hospital therapy arm. Home intravenous antibiotic therapy in patients with cystic fibrosis was a feasible, cost-effective alternative to receiving therapy in hospital. Although there was no clinical compromise associated with home therapy, there were advantages and disadvantages in terms of quality of life." ]

[ "8615350", "12412870", "1491608", "9396564", "15718356", "11102555", "2255573", "11483801", "17991642", "16382755", "10467999", "15812447", "15069395", "12032520" ]

[ "Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia.", "Dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation.", "First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula.", "Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids.", "Body composition in preterm infants who are fed long-chain polyunsaturated fatty acids: a prospective, randomized, controlled trial.", "The use of low-EPA fish oil for long-chain polyunsaturated fatty acid supplementation of preterm infants.", "Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates.", "Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.", "Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids.", "The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants.", "Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.", "Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid.", "Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants.", "Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula." ]

[ "Healthy preterm infants fed formula with long-chain n-3 fatty acids (n-3 LCFAs) from marine oil have better early visual acuity but lower plasma phosphatidylcholine (PC) arachidonic acid (AA) and growth than infants fed formula containing linolenic acid (LLA) as the sole n-3 fatty acid. This randomized, double-blind trial was designed to study the effects of a different source of n-3 LCFAs and a shorter feeding interval on visual acuity (by Teller Acuity Card) and growth of preterm infants (n = 59; 747-1275 g birth wt), some of whom required long periods of supplemental oxygen and developed bronchopulmonary dysplasia (BPD). Infants were studied at 0, 2, 4, 6, 9, and 12 mo past term. Plasma PC AA, and normalized weight, length, and head circumference were not influenced by BPD or n-3 LCFAs except that n-3 LCFA-supplemented infants weighed less at 6 (P<0.05) and 9 (P<0.01) mo and had smaller head circumferences at 9 mo (P<0.05). Compared with control infants, however, those fed n-3 LCFAs had lower weight-for-length at 2, 6, 9, and 12 mo (P<0.0003, P<0.0114, P<0.0008, and P<0.006, respectively). n-3 LCFAs improved early (2-mo) but not later acuity among infants without BPD (P<0.02). Regardless of diet, infants with BPD had poorer grating acuity at 2 (P<0.0002) and 4 (P<0.04) mo but not thereafter.", "To study the influence of dietary-supplied long-chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development, relating them to structural maturation. Other studies have suggested that dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants may enhance their visual development. The influence on structural brain development has never been evaluated.\n In a prospective, double-blind study, 42 formula-fed premature infants were randomized to be fed either a standard preterm formula without long-chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid (0.015 g/100 ml) and arachidonic acid (0.031 g/100 ml). Infants with significant cerebral damage, retinopathy, chronic disease or feeding problems were excluded. Follow-up was focused on assessment of cerebral myelination by MRI. Psychomotor, mental and visual development was analysed and flash-visual evoked potentials were recorded.\n It was found that progress of myelination, mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long-chain polyunsaturated fatty acids. At each test age, visual acuity was slightly better in the supplemented infants than in the non-supplemented infants, but the difference never reached significance level\n Supplementation of long-chain polyunsaturated fatty acids did not have a demonstrable positive influence on structural brain maturation. Related to this finding, in this small cohort of preterm infants without significant neurological damage, sample size being restricted by strict inclusion criteria and MRI procedures, no significant positive effects were found on psychomotor, mental and visual development.", "Very low birth weight (VLBW) infants (748-1390 g, n = 65) were randomly assigned to receive control or marine oil-supplemented formula when they achieved intakes > 454 kJ (110 kcal)/kg/d of a formula designed for VLBW infants. Study formulas with or without marine oil were provided until 79 wk of postconceptional age (PCA), first in a formula designed for preterm infants followed by a formula designed for term infants. Infants were studied at regular intervals through 92 wk PCA. Weight, length, and head circumference were determined by standardized procedures and normalized to the National Center for Health Statistics figures for growth of infants born at term of the same age and gender. Mean normalized weight, weight-to-length, and head circumference were greatest at 48 wk and decreased thereafter. The decline in normalized weight was greater in infants fed the marine oil-supplemented formula. Beginning at 40 wk, marine oil-supplemented infants compared to controls had significantly poorer Z-scores for weight, length and head circumference. In addition, birth order (negatively) and maternal height (positively) influenced weight and length achievement in infancy as shown previously in infants born at term.", "The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), have not been clearly defined. The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula (Preemie SMA) devoid of AA and DHA and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1% AA and 0.24 to 0.76% DHA. An analogous group of infants fed their mothers' breast milk and a breast milk fortifier (when indicated) was also studied. Erythrocyte membrane phospholipids were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine, and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids. From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32-1.1% AA and 0.24-0.76% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined.", "The objective of this study was to evaluate growth and body composition of premature infants who were fed formulas with arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) to 1 y of gestation-corrected age (CA). Preterm infants (750-1800 g birth weight and <33 wk gestational age) were assigned within 72 h of first enteral feeding to one of three formulas: control (n = 22), DHA+ARA from fish/fungal oil [DHA+ARA(FF); n = 20], or DHA+ARA from egg/fish oil [DHA+ARA(EF); n = 18]. Human milk feeding was allowed on the basis of the mother's choice. Infants were fed breast milk and/or preterm formulas with or without 0.26% DHA and 0.42% ARA to term CA followed by breast milk or postdischarge preterm formulas with or without 0.16% DHA and 0.42% ARA to 12 mo CA. Body composition was measured by dual-energy x-ray absorptiometry. There were no significant differences among the three study groups at any time point in weight, length, or head circumference. Bone mineral content and bone mineral density did not differ among groups. At 12 mo CA, infants who were fed DHA+ARA-supplemented formulas had significantly greater lean body mass (p < 0.05) and significantly less fat mass (p < 0.05) than infants who were fed the unsupplemented control formula. The DHA+ARA-supplemented formulas supported normal growth and bone mineralization in premature infants who were born at <33 wk gestation. Preterm formulas that had DHA+ARA at the levels and ratios in this study and were fed to 1 y CA led to increased lean body mass and reduced fat mass by 1 y of age.", "Because docosahexaenoic acid (DHA) may be an essential nutrient for the visual and early cognitive development of preterm infants, DHA enrichment of preterm formulas has been recommended. This randomized trial was designed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a standard formula. A reference group of breast-fed infants was studied concurrently. The fatty acid content of red blood cell (RBC) phospholipid was assessed at enrollment, hospital discharge, expected term, and 3 and 6 mo postterm. The DHA content of RBC phospholipid was higher in infants fed the enriched versus the standard formula at hospital discharge, expected term, and 3 and 6 mo postterm. However, compared with infants fed the standard formula, infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content (0.69 +/- 0.15% versus 0.25 +/- 0.12%, p < 0.001), and lower RBC phospholipid arachidonic acid content (15.1 +/- 0.93% versus 18.8 +/- 0.89%; p < 0.001). We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status, but results in worsening of n-6 fatty acid status. We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved.", "Retinal function was assessed by electroretinogram in 32 neonates randomly assigned to formulas of different omega-3 fatty acid content and in 10 infants fed human milk. All neonates had a birth weight of 1000-1500 g and were fed study diets from d 10 to 45 or discharge. Group A received formula containing predominantly 18:2 omega-6. Group B received a balanced mix of 18:2 omega-6 and 18:3 omega-3. Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 omega-3 content similar to that of human milk. The fatty acid composition of plasma and red blood cell (RBC) lipids were similar for all groups on entry but marked diet-induced differences were found after feeding the study diets. Group C was comparable to the human milk-fed group, but group A had lower 22:6 omega-3 and omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in plasma and RBC membranes. Cone function was not affected by dietary essential fatty acids. Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC omega-3 LCPUFA (r = -0.63, p less than 0.0001); 44% of the variance could be explained by RBC and plasma omega-3 LCPUFA content.(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development.\n Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference.\n Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants </=1250 g. When Spanish-speaking infants and twins were excluded from the analyses, the MacArthur Communicative Development Inventory revealed that control infants (LS means +/- SE, 94.1 +/- 2.9) had lower vocabulary comprehension at 14 months' CA than AA+DHA (fish/fungal) infants (100.6 +/- 2.9) or AA+DHA (egg-TG/fish) infants (102.2 +/- 2.8). There were no consistent differences in weight, length, head circumference, or anthropometric gains.\n These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months' CA.", "Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment.\n We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs.\n Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated.\n Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis.\n By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.", "Preterm infants may be born with deficits of both docosahexaenoic acid (DHA) and arachidonic acid (AA), but studies on supplementation of DHA and AA for preterm infants are limited.\n Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind, randomized, comparative study. Infants over 2000 g body weight, over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months. Sixteen infants received Neoangelac Plus with AA and DHA supplementation. Eleven infants received Neoangelac without AA and DHA supplementation. The babies had scheduled physical examinations and their cognitive development, visual acuity, and vital signs to be checked. Adverse events were also recorded.\n The mean Mental Development Index (MDI) scores for the supplementation and non-supplementation groups were 96.1 +/- 8.6 and 91.7 +/- 10.4 respectively at 6 months and 98.7 +/- 8.0 and 90.5 +/- 6.9 respectively at 1 year. The mean Physical Development Index (PDI) scores of these two groups were 102.2 +/- 10.5 and 95.4 +/- 13.2 respectively at 6 months and 98.0 +/- 5.8 and 86.7 +/- 11.1 respectively at 1 year. By repeated measures ANOVA, significant differences existed between groups for MDI and PDI (p = 0.020 and 0.008). However, there were no differences in visual acuity, physical examination variables or vital signs between these two groups. No obvious adverse effects were observed during the study period.\n These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA.", "The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk.\n In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133).\n Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group.\n The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.", "To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) until 92 weeks postmenstrual age (PMA), with follow-up to 118 weeks PMA.\n This double-blinded study of 361 preterm infants randomized across three formula groups: (1) control, no supplementation; (2) algal-DHA (DHA from algal oil, ARA from fungal oil); and (3) fish-DHA (DHA from fish oil, ARA from fungal oil). Term infants breast-fed > or =4 months (n = 105) were a reference group. Outcomes included growth, tolerance, adverse events, and Bayley development scores.\n Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA. The algal-DHA group was significantly longer than the control group at 48, 79, and 92 weeks PMA and the fish-DHA group at 57, 79, and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA. Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group. Supplementation did not increase morbidity or adverse events.\n Feeding formulas with DHA and ARA from algal and fungal oils resulted in enhanced growth. Both supplemented formulas provided better developmental outcomes than unsupplemented formulas.", "To test the efficacy and safety of long-chain polyunsaturated fatty acid (LCPUFA) supplementation with gamma-linolenic acid, a precursor of arachidonic acid, and docosahexaenoic acid in preterm infants.\n Preterm (<35 weeks, < or =2000 g birth weight) infants (n=238) randomly assigned to unsupplemented or LCPUFA-supplemented formula to 9 months after term. The main outcome measure was the Bayley Mental and Psychomotor Indexes (MDI, PDI) at 18 months after term. Safety outcome measures were anthropometry (9 and 18 months), feed tolerance, infection, and clinical complications.\n There were no significant differences in neurodevelopment between groups overall. In preplanned subgroup analyses, LCPUFA-supplemented boys had significantly higher Bayley MDI than did control boys (difference, 5.7 points; 95% CI, 0.3 to 11.1; P=.04). LCPUFA-supplemented infants showed significantly greater weight gain (difference, 310 g; 95% CI, 30 to 590 g; P=.03) and length gain (difference, 1.0 cm; 95% CI, 0.02 to 1.9; P=.05) between birth and 9 months, with greater effect in boys (weight difference at 9 months, 510 g; 95% CI, 80 to 930 g; P=.02; length difference at 18 months, 1.8 cm; 95% CI, 0.1 to 1.8; P=.03).\n This trial, using the strategy of providing gamma-linolenic acid as a source of arachidonic acid, showed efficacy for growth and for neurodevelopment in boys, with no adverse effects. These data have important implications for LCPUFA-supplementation strategy in preterm infants.", "To determine if docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation influences growth or visual acuity of formula-fed premature infants.\n Double-blind, multi-center study of 194 premature infants given preterm formula with no DHA or ARA (control), 0.15% energy DHA, or 0.14% DHA + 0.27% ARA from single-cell triglycerides for at least 28 days and then fed term formula (no DHA or ARA) to 57 weeks postmenstrual age (PMA), with 90 breast-fed term infants as reference.\n Infants fed DHA+ARA formula gained weight significantly faster (post-hoc analysis) during preterm formula feeding than control infants (34.7 vs. 30.7 g/d) and had weights and weight:length ratios not different from term breast-fed infants at 48 and 57 weeks PMA. Infants fed control or DHA formula had lower body weights than term infants. Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40, 48, and 57 weeks PMA (r = 0.19 to 0.24, P =.004-.02). Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events.\n Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects." ]

[ "3102779", "7781368", "6441010" ]

[ "Efficacy of metoclopramide as an adjunct to duodenal placement of small-bore feeding tubes: a randomized, placebo-controlled, double-blind study.", "Enteral feeding tube placement success with intravenous metoclopramide administration in ICU patients.", "When does metoclopramide facilitate transpyloric intubation?" ]

[ "We examined whether metoclopramide would improve the success rate of transpyloric intubation of a weighted Corpak feeding tube when fluoroscopic guidance is not used. Seventy patients were randomized in a prospective, double-blind fashion to receive either placebo (n = 35) or metoclopramide, 10 mg (n = 35) parenterally, administered immediately after the feeding tube was inserted. Tube location was determined independently by two observers who examined radiographs obtained after barium was instilled via the tube. There was no significant increase in the success rate of duodenal intubation in the total group following metoclopramide, 60%, compared to placebo, 49%. However, analysis of subgroups among the placebo-treated patients revealed that diabetes mellitus, but not other medical conditions, decreased the success rate for duodenal intubation, 20 vs 60% (p less than 0.05). Among diabetic patients, metoclopramide resulted in a significant increase in duodenal placement compared to placebo (p less than 0.05). We conclude that parenteral metoclopramide significantly increases the frequency of transpyloric intubation with small feeding tubes without fluoroscopic guidance in diabetic patients but not in nondiabetic patients.", "The purpose of this study was to determine if intravenous push metoclopramide would facilitate immediate transpyloric passage of a small-bore feeding tube without fluoroscopy or endoscopy.\n Prospective, randomized trial.\n One hundred five medical and surgical ICU patients at a community teaching hospital.\n Patients were randomized to receive 10 mg of metoclopramide 10 min before tube insertion or no medication.\n Successful placement was stated as radiologically verified transduodenal tube location.\n A 54% success rate was shown with administration of the drug with 46% success for the control. Chi square analysis of the success rate showed no significant relationship between administration of metoclopramide and successful tube placement (p = 0.38). Increasing years of physician training was the only variable associated with successful placement (p = 0.003). No association was found between successful tube placement and presence of endotracheal tube, tracheostomy, or cervical immobility, nor any interaction of metoclopramide with these variables.\n Intravenous metoclopramide, 10 mg, administered 10 min prior to intubation with a small-bore feeding tube (10F), was ineffective in facilitating transpyloric intubation.", "Postpyloric feeding probably reduces the incidence of tracheobronchial aspiration and improves feeding tolerance. However, duodenal intubation is often unsuccessful in critically ill patients due to gastric atony. Metoclopramide improves gastric emptying. In a pilot study, 12 adult patients were administered 10 to 20 mg of intravenous metoclopramide after weighted nasal feeding tubes had failed to spontaneously pass distal to the pylorus. In no patient did metoclopramide induce transpyloric passage of the tube. A randomized prospective study involving 10 adult patients was conducted to examine the effect of preinsertion intravenous metoclopramide on transpyloric intubation. All patients had failed to achieve spontaneous duodenal intubation. Five patients received 20 mg of metoclopramide 10 min prior to nasal insertion of a weighed feeding tube. Five control patients received no premedication. Four metoclopramide patients achieved duodenal intubation immediately. In none of the control patients did transpyloric intubation occur (p = 0.048). Metoclopramide, administered after nasogastric intubation, is ineffective in promoting transpyloric advancement of feeding tubes. There is a significant increase in transpyloric intubation when metoclopramide is administered prior to tube insertion." ]

[ "15464768", "8610779", "3620398" ]

[ "High and low dose oxytocin in augmentation of labor.", "Low-dose versus high-dose oxytocin augmentation of labor--a randomized trial.", "A randomized control study of oxytocin augmentation of labour. 1. Obstetric outcome." ]

[ "To compare the efficacy and safety of high dose oxytocin in the augmentation of labor.\n Two hundred pregnant women requiring augmentation of labor were randomly assigned to receive oxytocin by either a low dose protocol (1.5 microm/min initially, increased by 1.5 microm/min every 30 min) or a high dose protocol (4.5 microm/min initially, increased by 4.5 microm/min every 30 min).\n High dose of oxytocin was associated with a significant shortening of labor 4 (1.10-10) vs. 6 (1-10) h, p<0.0001 without a significant difference in cesarean delivery rate, neonatal and maternal outcome.\n The use of high dose oxytocin is associated with significantly shorter labor without any adverse fetal and maternal effects.", "Our purpose was to compare the efficacy and safety of low-dose versus high-dose oxytocin regimens in the augmentation of labor.\n Three hundred ten term pregnancies requiring augmentation of labor underwent randomization to receive either a low-dose or high-dose oxytocin augmentation regimen. Maternal demographics, labor-delivery data, and neonatal outcome were compared.\n The high-dose oxytocin group had a significantly lower cesarean section rate, regardless of parity (10.4% vs 25.7%, p < 0.001), with no differences in maternal complications and neonatal outcomes. The time needed to correct the labor abnormality was also significantly decreased (1.24 +/- 1.4 hours vs 3.12 +/- 1.6 hours, p < 0.001) in the high-dose group.\n The use of high-dose oxytocin regimen benefits both nulliparous and multiparous women requiring labor augmentation by significantly lowering both the time necessary to correct the labor abnormality and the need for cesarean section.", "Sixty women who were progressing slowly in spontaneous labour were assigned at random to three management protocols. Group 1 were observed without the use of oxytocin for 8 h while groups 2 and 3 were managed with a low-dose and high-dose oxytocin protocol respectively. The caesarean section rates were not significantly different between the three groups: 45%, 35% and 26% respectively. Cervical dilatation rate increased significantly after oxytocin infusion in both treatment groups compared with controls. The 'delay-to-delivery' interval and second stage duration were significantly shorter in the high-dose group than in the control group. There were no measurable differences in the condition of the newborn infants between the three groups." ]

[ "10735462", "8215566" ]

[ "The haemodynamic effects of dopamine and volume expansion in sick preterm infants.", "Randomised controlled trial of plasma protein fraction versus dopamine in hypotensive very low birthweight infants." ]

[ "To determine the haemodynamic effects of dopamine and volume expansion in preterm neonates. Effect parameters were mean arterial blood pressure (MABP), left ventricular output (LVO) and global cerebral blood flow (CBF).\n In a randomised, clinical control trial 36 preterm neonates were randomised to receive either dopamine 5 microg/kg per min, volume expansion with albumin 20% 15 ml/kg or no treatment. Parameters were measured before and 2 h after initiation of treatment.\n Dopamine was effective in increasing MABP; both treatments increased LVO, whereas no significant difference between the treatment groups and the control group could be demonstrated with regard to CBF.\n No effect on global cerebral blood flow could be demonstrated in this study, despite significant effects on systemic circulatory parameters. However, the variance on the measurement of cerebral blood flow indicates that a small but clinically significant effect may have been overlooked.", "Around 20% of very low birthweight infants admitted to a neonatal intensive care unit become hypotensive within 24 hours of their admission. Standard treatment is either expansion of the circulating volume by the infusion of plasma protein fraction or by using dopamine to improve cardiac function. The purpose of this study was to investigate by a randomised controlled trial which was the most appropriate treatment. Thirty nine infants were randomised to receive either plasma protein fraction or dopamine as first line treatment if they became hypotensive within 24 hours of admission to the neonatal intensive care unit. Seventeen of 19 (89%) infants responded to dopamine, whereas only 9/20 (45%) responded to plasma protein fraction. The median dose of dopamine needed to increase the blood pressure to at least the 10th centile was 7.5 micrograms/kg/min and was infused for a median duration of 18 hours. These observations suggest that dopamine should be used earlier in the treatment of these infants than has previously been recommended." ]

[ "8411891", "15162273", "10690817", "16272048", "10476515", "14750378", "9113011", "12770957", "9437309", "2872913", "15148202", "15051198", "15878068", "9826042", "10463407", "9379368", "10711881" ]

[ "[Comparison of complications after intra- and extracapsular cataract extraction with lens implantation. Results of a prospective, randomized, clinical study].", "Comparing phacoemulsification and extracapsular cataract extraction in eyes with pseudoexfoliation syndrome, small pupil, and phacodonesis.", "The South Asian cataract management study: complications, vision outcomes, and corneal endothelial cell loss in a randomized multicenter clinical trial comparing intracapsular cataract extraction with and without anterior chamber intraocular lens implantation.", "Comparison of endothelial cell loss and surgically induced astigmatism following conventional extracapsular cataract surgery, manual small-incision surgery and phacoemulsification.", "Postoperative inflammation: extracapsular cataract extraction versus phacoemulsification.", "Cost analysis of cataract surgery with intraocular lens implantation: a single blind randomised clinical trial comparing extracapsular cataract extraction and phacoemulsification.", "Randomised controlled trial of anterior-chamber intraocular lenses.", "Extracapsular cataract surgery compared with manual small incision cataract surgery in community eye care setting in western India: a randomised controlled trial.", "The Madurai Intraocular Lens Study. II: Clinical outcomes.", "Cataract surgery: interim results and complications of a randomised controlled trial. Oxford Cataract Treatment and Evaluation Team (OCTET).", "A comparison of anterior and posterior chamber lenses after cataract extraction in rural Africa: a within patient randomised trial.", "Effect of cataract surgery on the corneal endothelium: modern phacoemulsification compared with extracapsular cataract surgery.", "Safety and efficacy of phacoemulsification compared with manual small-incision cataract surgery by a randomized controlled clinical trial: six-week results.", "Randomized study of the blood-aqueous barrier reaction after phacoemulsification and extracapsular cataract extraction.", "Ultrasound biomicroscopy examination of intraocular lens haptic position after phacoemulsification with continuous curvilinear capsulorhexis and extracapsular cataract extraction with linear capsulotomy.", "Corneal endothelial function after extracapsular cataract extraction and phacoemulsification.", "Phacoemulsification versus extracapsular cataract extraction in patients with diabetes." ]

[ "The postoperative complications of ICCE with ACL implantation are compared with those of ECCE and PCL. Our clinical experience with ICCE and ACL implantation can not confirm the widespread rejection of this method.\n A prospective, randomized, clinical study with participation of medical statisticians was performed. A total of 190 patients with ICCE and ACL and 170 patients with ECCE and PCL were followed up for 2 years. The follow-up examinations were performed upon dismission from the hospital, after 6, 12 and 24 months. The data were compiled in a computer program designed for this study and evaluated by the statisticians. The surgical procedures and the surgeons were defined prior to the beginning of patient recruitment.\n ICCE with ACL shows much less postoperative complications as usually emphasized. There were only 2 (1.2%) of retinal detachment and no case of corneal decompensation. Cystoid macular edema 8 (4.7%), postoperative vitreous prolaps into the anterior chamber 4 (2.3%) and spontaneous complaints of pain 16 (9.4%) occurred in a low percentage after ICCE with ACL. These complications did not occur after ECCE with PCL. The patients with ECCE and PCL showed capsular fibrosis in 48 (28%) making it the most frequent complication of the whole study. 33% of these patients required YAG-laser capsulotomy. Since retinal detachment occurs in 2.5% after YAG-laser capsulotomy we can not regard capsular fibrosis as a totally harmless complication. It is noteworthy that visual acuity is almost identical 1 year after surgery in both methods.\n The results of this study show that the evaluation of ICCE with ACL is too negative. The elimination of postoperative complications in this method is more difficult. ECCE with PCL is burdened by frequent capsular fibrosis. Visual acuity is almost the same in both methods 1 years after the operation. ACL-implantation remains our method of choice for secondary implantation in patients with an intact iris diaphragm.", "This study aims to compare the frequency of intraoperative and postoperative complications between the modern phacoemulsification technique and the extracapsular cataract extraction technique in patients with pseudoexfoliation syndrome.\n A prospective randomized study comprised 94 eyes with cataract, pseudoexfoliation syndrome, small pupil and slight to moderate phacodonesis. These eyes were randomly assigned into two groups. In the first group all patients (47 eyes) were operated on using a standard phacoemulsification technique (iris hooks, anterior capsule staining and capsular tension ring after capsulorhexis), while in the second group all patients (47 eyes) underwent a classic extracapsular cataract extraction. The main outcome measures were the frequency of intraoperative zonular tears, capsular rupture, vitreous loss and corneal edema, as well as the best-corrected visual acuity.\n Intraoperative zonular separation was recorded in one eye (2.1 %) and in 15 eyes (31.9 %) for the first and second groups, respectively (P < 0.001). Posterior capsule rupture with or without zonular separation occurred in two eyes (4.2 %) of the first group and in eight eyes (17.0 %) of the second group (P < 0.05). Vitreous loss also had a higher rate in the second group (17.0 % versus 4.2 %, P < 0.05). The postoperative difference in best-corrected visual acuity was also significant between the two groups, being higher in patients operated on using phacoemulsification technique (P < 0.001).\n In the difficult cases of cataract associated with pseudoexfoliation syndrome, small pupil and phacodonesis, the modern small-incision cataract surgery provides better results with a low rate of intraoperative and postoperative complications when compared with the extracapsular cataract extraction technique.", "To determine clinical outcomes of primary intracapsular cataract surgery with and without implantation of anterior chamber lenses.\n A multicenter randomized clinical trial.\n One thousand two hundred twenty-nine male and female patients 40-75 years of age with senile cataract.\n Study patients were recruited from screening eye camps and outpatient clinics. Randomization to the two treatment groups was performed after screening for predetermined inclusion and exclusion criteria. Demographics, visual acuity, intraocular pressures, and corneal endothelial cell data were recorded before surgery and at 6 weeks, 12 months, and 24 months after surgery. Monitoring of the study was secured by a standardized image documentation procedure on all patients using the IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was performed with the Cell Soft software (Topcon Corporation, Japan).\n Visual acuity and central corneal endothelial cell loss.\n The patients were randomized to intraocular lens (IOL; n = 616) and no IOL (n = 613) implantation. Surgical complications were reported in 177 (14.4%) patients (IOL = 14.8%; no IOL = 14.0%). The most frequent complication observed was vitreous loss which occurred in 10.3% of eyes (IOL = 11.2%; no IOL = 9.5%). At the final examination (2 years after surgery), 88% of the operated eyes had a best corrected vision of 6/18 or better (IOL = 88.8%; no IOL = 86.6%). Analysis of corneal endothelial cell data showed a small but significantly greater cell loss 6 weeks after surgery in eyes with IOL compared with those without IOL, but no overall difference was found between the treatment groups in the long term follow-up.\n The findings indicate that there is a rationale for the use of anterior chamber intraocular lenses in primary intracapsular cataract surgery.", "To compare the surgically induced astigmatism (SIA) and endothelial cell loss following conventional extracapsular cataract surgery (ECCE), manual small-incision cataract surgery (Blumenthal technique)(SICS) and phacoemulsification (PE) with non-foldable intraocular lens implantation.\n 186 cataractous eyes with nuclear sclerosis grade 3 or less were randomized to undergo ECCE, SICS or PE with intraocular lens (non-foldable) implantation after a detailed pre-operative assessment. Keratometry and specular microscopy were performed pre-operatively and 6 weeks postoperatively. Surgically induced astigmatism was calculated using the rectangular coordinate method (Holladay et al.).\n Mean endothelial cell loss was similar for all three groups (p = 0.855); ECCE induced a loss of 4.72% (SD: 13.07); SICS 4.21% (SD: 10.29) and PE 5.41% (SD: 10.99). Mean SIA was 1.77D (1.61D) for the ECCE group, 1.17D (0.95D) for the SICS group and 0.77D (0.65D) for the PE group (p = 0.001). The magnitude of the difference between the SICS and the PE group was 0.4D.\n PE induced less astigmatism than SICS and ECCE in this study but the magnitude of the difference between SICS and PE was small. There was no significant difference in endothelial cell loss between the three groups.", "To quantitatively compare postoperative inflammation after extracapsular cataract extraction (ECCE) with that after phacoemulsification in an Asian population.\n Singapore National Eye Center, Singapore.\n In this prospective, randomized, double-masked clinical trial, patients having cataract surgery were randomized to receive ECCE (n = 16) or phacoemulsification (n = 18). Diabetics were excluded. Two surgeons performed both types of surgery and implanted a 6.0 mm optic intraocular lens. Inflammation was assessed qualitatively by slitlamp grading of cells and flare and quantitatively using the Kowa flare meter. One independent postoperative investigator performed the slitlamp examination and laser flare meter readings.\n The ECCE and phacoemulsification groups were comparable (P > .05) in age, sex, ethnicity, and preoperative flare levels. The combined slitlamp inflammatory scores (anterior chamber cells and flare) and mean laser flare meter readings showed the ECCE group had significantly higher mean flare measurements than the phacoemulsification group at days 4 (P = .0012), 8 (P = .0013), 15 (P = .0013), 30 (P = .0004), and 60 (P = .0164). Flare levels in the ECCE group returned to preoperative values by the second month; the phacoemulsification group achieved preoperative levels by 1 month. The clinical inflammatory assessment score correlated closely to the flare level readings.\n Phacoemulsification induced less inflammation than ECCE, with the difference most marked in the first month after surgery.", "A randomised single blinded clinical trial to compare the cost of cataract surgery between extracapsular cataract extraction (ECCE) and phacoemulsification (PEA) was conducted at Hospital Universiti Kebangsaan Malaysia (HUKM) between March and December 2000. A total of 60 patients were included in this study. The cost of a cataract surgery incurred by hospital, patients and households up to two months after discharge were included. The costs of training, loss of patients' income after discharge and intangible costs were excluded. Results showed that the average cost for one ECCE operation is RM1,664.46 (RM1,233.04-RM2,377.64) and for PEA is RM1,978.00 (RM1,557.87-RM3,334.50). During this short period of follow up, it can be concluded that ECCE is significantly cheaper than PEA by an average difference of RM 313.54 per patient (p < 0.001). Cost of equipment and low frequency of PEA technique done in HUKM were the two main reasons for the high unit cost of PEA as compared to ECCE.", "There are an estimated 16 million people blind in both eyes with cataracts. Most live in rural areas of developing countries where surgical resources are scarce. There is no consensus on the most appropriate type of intraocular lens in situations where high-volume low-cost surgery is required. This study was undertaken to evaluate the safety of multiflex open-loop anterior-chamber lenses (ACIOLs).\n 2000 people attending Lahan Eye Hospital, southern Nepal, with bilateral cataracts reducing vision to 6/36 or less were randomly allocated to receive standard surgery--intracapsular extraction (ICCE) with aphakic correction--or ICCE with an ACIOL in their first operated eye. The primary outcome was a visual acuity of less than 6/60 in the operated eye at 1 year follow-up. Visual acuity was measured for 91% of the cohort at 1 year. The sample size was estimated to detect a doubling in poor visual outcome from an estimated rate of 4% in the standard surgery (control) group.\n The median (range) time taken to do the surgery was 6.0 (3.0-17.2) min for the ACIOL group and 4.1 (2.4-10.3) min for the control group. 1 year after surgery, 5.0% of the ACIOL group and 5.4% of controls had functional vision less than 6/60 (OR 0.93 [0.60-1.43], p = 0.71). The causes of poor vision in the ACIOL and control groups were: correctable refractive error (22 and 29), uveitis/secondary glaucoma (13 and two), endophthalmitis (four and seven), pre-existing eye disease (four and five), retinal detachment (none and four), cystoid macular oedema (two and none), corneal ulcer (one and one), and corneal decompensation (none and one).\n This study provides evidence that, in rural areas of developing countries, multiflex open-loop ACIOLs can be implanted safely by experienced ophthalmologists after routine ICCE, avoiding the disadvantages of aphakic spectacle correction. Further follow-up is planned.", "To study \"manual small incision cataract surgery (MSICS)\" for the rehabilitation of cataract visually impaired and blind patients in community based, high volume, eye hospital setting; to compare the safety and effectiveness of MSICS with conventional extracapsular cataract surgery (ECCE).\n In a single masked randomised controlled clinical trial, 741 patients, aged 40-90 years, with operable cataract were randomly assigned to receive either MSICS or ECCE and operated upon by one of eight participating surgeons. Intraoperative and postoperative complications were graded and scored according to the Oxford Cataract Treatment and Evaluation Team recommendations. The patients were followed up at 1 week, 6 weeks, and 1 year after surgery and their visual acuity recorded.\n This paper reports outcomes at 1 and 6 weeks. 706 of the 741(95.3%) patients completed the 6 week follow up. 135 of 362 (37.3%) of ECCE group and 165 of 344 (47.9%) of MSICS group had uncorrected visual acuity of 6/18 or better after 6 weeks of follow up. 314 of 362 (86.7%) of ECCE group and 309 of 344 (89.8%) of MSICS group had corrected postoperative vision of 6/18 or better. Four of 362 (1.1%) of ECCE group and six of 344 (1.7%) of MSICS group had corrected postoperative visual acuity less than 6/60. There were no significant differences between the two groups for intraoperative and severe postoperative complications.\n MSICS and ECCE are both safe and effective techniques for treatment of cataract patients in community eye care settings. MSICS needs similar equipment to ECCE, but gives better uncorrected vision.", "To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG).\n In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists.\n At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE-AG group and 7.7% in the ECCE group (P < .001). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001).\n Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.", "A randomised controlled trial in progress for more than five years, with no loss to follow-up (except death), assessed 333 eyes treated by three methods of cataract surgery. They were (A) intracapsular extraction and contact lens usage, (B) intracapsular extraction and implantation of an iris supported lens (Federov I), and (C) extracapsular extraction and implantation of an iridocapsular lens (Binkhorst 2-loop). The purpose of the paper is to report interim visual results, complications, and corneal endothelial cell loss. More eyes in groups A (contact lens) and C (extracapsular + implant) achieved better visual acuity than in group B (intracapsular + Federov lens), which also had more postoperative complications. Both implant groups lost more endothelial cells than the non-implant group, which did not differ significantly from group B before one year.", "Extracapsular cataract extraction (ECCE) with a posterior chamber intraocular lens (PC IOL) is the preferred method of cataract surgery in developed countries. However, intracapsular cataract extraction (ICCE) with an anterior chamber lens (AC IOL) may be appropriate in rural Africa. A randomised controlled trial was carried out to compare these surgical strategies.\n Participants over 50 years requiring bilateral cataract surgery were recruited from outreach clinics in rural north and east Uganda. One eye was randomly allocated to AC IOL or PC IOL, the other eye being allocated to the second strategy. The main outcome measure was WHO distance visual acuity (VA) category after a minimum of 1 year. Secondary outcomes were numbers and causes of complications and refractive corrections.\n Of the 110 participants recruited, 98 (89%) were assessed at least 1 year after the operation (median follow up 17.5 months). Nine eyes randomised to PC IOL were converted to AC IOL; one eye randomised to AC IOL inadvertently received PC IOL. There was no difference in VA between 95 pairs of eyes for which data for both eyes were available (uncorrected VA, p = 0.26; corrected VA, p = 0.59). 80 (82%, 95% CI 73 to 89) and 82 (84%, 95% CI 75 to 90) eyes randomised to AC IOL and PC IOL respectively had corrected VA of 6/18 or better. 16 (16%, 95% CI 10 to 25) and eight (8%, 95% CI 4 to 15) eyes respectively had secondary procedures or other complications.\n Where both strategies are available, ECCE with PC IOL should be first choice because of fewer complications. Where ECCE with PC IOL is not immediately feasible, ICCE with AC IOL is an acceptable interim technique.", "To investigate whether modern phacoemulsification surgery results in more damage to the corneal endothelium than extracapsular cataract extraction (ECCE), and to examine which preoperative, operative, and postoperative factors influence the effect of cataract surgery on the endothelium.\n Randomized controlled trial.\n Five hundred patients 40 years or older were randomized into 2 groups (ECCE, 249; phacoemulsification, 251).\n Central corneal endothelial cell counts, coefficient of variation of cell size, and hexagonality were assessed before surgery and up to 1 year postoperatively.\n Endothelial cell count.\n Four hundred thirty-three patients completed the trial. The initial preoperative mean cell count for the entire sample was 2481 (standard error [SE]: 18.6), reduced at 1 year postoperatively to 2239 (SE: 23.5). An average 10% reduction in cell count was recorded by 1 year postoperatively. There was no such change in hexagonality or in the coefficient of variation. There was no significant difference in overall percentage cell loss between the 2 treatment groups. Factors associated with excessive cell loss (> or =15% by 1 year) were a hard cataract (odds ratio [OR]: 2.1, 95% confidence limits: 1.1-4.1; P = 0.036), age (OR: 1.04, P = 0.005), and capsule or vitreous loss at surgery (OR: 2.38, P = 0.106). Phacoemulsification carried a significantly higher risk (OR: 3.7, P = 0.045) of severe cell loss in the 45 patients with hard cataracts relative to ECCE (52.6% vs. 23.1%; chi-square test, P = 0.041), with both procedures achieving similar postoperative visual acuity outcomes.\n No significant difference in overall corneal endothelial cell loss was found between these 2 operative techniques. The increased risk of severe cell loss with phacoemulsification in patients with hard cataracts suggests that phacoemulsification may not be the optimal procedure in these cases, and that ECCE should be preferred.", "To compare the efficacy, safety, and refractive errors of astigmatism after cataract surgery by phacoemulsification and manual small-incision cataract surgery techniques.\n Masked randomized control clinical trial.\n Four hundred eyes of 400 patients, 1:1 randomization with half in each arm of the trial.\n A total of 400 eyes was assigned randomly to either phacoemulsification or small-incision groups after informed consent and were operated on by 4 surgeons. They were masked to the technique of surgery before, during, and after cataract surgery and followed up to 1 year after surgery. The intraoperative and postoperative complications, uncorrected and best-corrected visual acuity, and astigmatism were recorded at 1 and 6 weeks postoperatively.\n The proportion of patients achieving visual acuity better than or equal to 6/18 with and without spectacles after cataract surgery in the operated eye up to 6 weeks, postoperative astigmatism, and complications during and after surgery.\n This article reports clinical outcomes up to 6 weeks. Three hundred eighty-three of 400 (95.75%) patients completed the 1-week follow-up, and 372 of 400 (93%) patients completed the 6-week follow-up. One hundred thirty-one of 192 (68.2%) patients in the phacoemulsification group and 117 of 191 (61.25%) patients in the small-incision group had uncorrected visual acuity better than or equal to 6/18 at 1 week (P = 0.153). One hundred fifty of 185 (81.08%) patients of the phacoemulsification group and 133 of 187 (71.1%) patients of the small-incision group (P = 0.038) were better than or equal to 6/18 at the 6-week follow-up for presenting visual activity. Visual acuity improved to > or = 6/18 with best correction in 182 of 185 patients (98.4%) and 184 of 187 (98.4%) patients (P = 0.549), respectively. Poor outcome (postoperative visual acuity < 6/60) was noted in 1 of 185 (0.5%) in the phacoemulsification group and none in the small-incision group. The mode of astigmatism was 0.5 diopters (D) for the phacoemulsification group and 1.5 D for the small-incision group, and the average astigmatism was 1.1 D and 1.2 D, respectively. There was an intra-surgeon variation in astigmatism. The phacoemulsification group had 7 posterior capsular rents compared with 12 in the small-incision group, but the phacoemulsification group had more corneal edema on the first postoperative day.\n Both the phacoemulsification and the small-incision techniques are safe and effective for visual rehabilitation of cataract patients, although phacoemulsification gives better uncorrected visual acuity in a larger proportion of patients at 6 weeks.", "To compare the blood-aqueous barrier (BAB) breakdown after endocapsular phacoemulsification and extracapsular cataract extraction (ECCE).\n Forty-two patients (64-82 years) enrolled for cataract surgery were randomly assigned to phacoemulsification (group I) or ECCE (group II). Patients with pseudoexfoliation syndrome, small pupils, glaucoma, uveitis, dark brown irides, diabetes, treatment with eye drops or anti-inflammatory drugs were excluded. In group I the patients were operated with continuous curvilinear capsulorhexis (CCC), phacoemulsification and implantation of a poly-(methyl methacrylate) (PMMA) intraocular lens (IOL) through a 5.2 mm self-sealing incision. In group II linear capsulotomy, nucleus expression and PMMA IOL implantation through a large incision (10-11 mm) were performed. The incision was sutured. Before surgery and three days and three months after surgery postoperative inflammation and BAB reaction were measured by laser flare photometry and anterior chamber fluorophotometry after intravenous administration of fluorescein. The BAB diffusion coefficient was calculated. Laser flare photometry was performed also after one and two years.\n According to fluorophotometry, ECCE induced significantly more postoperative BAB breakdown than did phacoemulsification at three days (p=0.00016) and three months (p=0.00829). Laser flare photometry showed more inflammation in the ECCE group than in the phacoemulsification group at three days postoperatively (p=0.00005).\n This study suggests that cataract surgery performed with a small, self-sealing incision, CCC and phacoemulsification induces a reduced surgical trauma with less BAB breakdown compared to ECCE using a large sutured incision, linear capsulotomy and nucleus expression.", "Intraocular lens (IOL) haptic position in 35 eyes that had undergone cataract surgery was examined with ultrasound biomicroscopy (UBM).\n In a prospective randomized study the patients were operated by phacoemulsification using continuous curvilinear capsulorhexis (CCC) (group I) or by extracapsular cataract extraction (ECCE) using linear capsulotomy (group II). Ultrasound biomicroscopy was used to localize both haptics of the implanted intraocular lenses and to measure anterior chamber depth (ACD), iris thickness and anterior chamber angle. The inflammatory reaction in the anterior chamber was assessed with laser flare photometry. Slit lamp examination was performed.\n Both IOL haptics were found in the lens capsule in all 18 eyes in group I. In group II one of the haptics was located out of the capsule in 7 of 17 eyes (41%). The difference is statistically significant (p=0.01). Postoperatively mean ACD measured with the UBM was 4.06+/-0.30 mm in group I and 3.64+/-0.24 mm in group II (p=0.00025).\n The UBM examinations indicate that phacoemulsification with continuous curvilinear capsulorhexis is a more reliable technique than ECCE with linear capsulotomy to achieve implantation of the intraocular lens haptics in the capsular bag.", "To compare the morphology and function of the corneal endothelium in the early postoperative period after extracapsular cataract extraction (ECCE) and phacoemulsification.\n University Eye Clinic of Trieste, Italy.\n In this prospective, randomized study of patients scheduled for cataract surgery, 40 patients were divided into two groups of 20 patients each. Group 1 had ECCE and Group 2, phacoemulsification; both had capsular bag intraocular lens (IOL) implantation. Preoperatively and 7 and 30 days postoperatively, a complete ophthalmological examination, endothelial specular microscopy, ultrasonic pachymetry, and anterior segment fluorophotometry were done. Visual acuity, endothelial cell density, cell size variation coefficient, corneal thickness, endothelial permeability coefficient, and endothelial pump function were studied.\n Visual acuity was better 7 days after phacoemulsification than after ECCE, but no differences were observed after 30 days. No significant differences in postoperative loss of endothelial cells were found between the two groups. Coefficient of variation in size, corneal thickness, and endothelial permeability significantly increased in both groups 7 days postoperatively, but only in the ECCE group 30 days postoperatively; the differences between the two groups were statistically significant. Endothelial pump function significantly increased after 7 days in only the phacoemulsification group.\n Functional endothelial failure occurred in the early period after ECCE. Phacoemulsification seemed to minimize postoperative functional damage to the endothelium.", "To compare phacoemulsification with extracapsular cataract surgery in patients with diabetes and to identify determinants of postoperative visual acuity.\n Prospective, randomized, paired-eye trial.\n Forty-six patients with diabetes and bilateral cataract.\n Patients were allocated to phacoemulsification surgery with silicone intraocular lens to one randomly determined eye, and extracapsular cataract surgery with 7-mm polymethylmethacrylate intraocular lens to the other.\n Logarithm of minimum angle of resolution visual acuity (logMAR VA), incidence of clinically significant macular edema (CSME), retinopathy progression, indices of anterior segment inflammation, and incidence of capsulotomy.\n Compared with eyes undergoing phacoemulsification, eyes managed with extracapsular surgery had more anterior chamber cells (P = 0.0004) and flare (P = 0.007) 1 week after surgery and a higher incidence of posterior synechiae (P = 0.04) and intraocular lens deposits (P < 0.0005) in the first postoperative year. The need for posterior capsulotomy was greater in eyes undergoing extracapsular surgery (16 of 46 vs. 5 of 46, P = 0.01). No difference in incidence of postoperative CSME, progression of retinopathy, or development of high-risk proliferative retinopathy was identified between techniques (P = 1.0, 0.8, and 0.2). Median 1-year logMAR VA was worse in eyes undergoing extracapsular surgery (0.08 vs. 0.06, P = 0.02), especially in those with retinopathy (0.14 vs. 0.08, respectively; P = 0.01). The presence or absence of CSME at the time of surgery was the most significant determinant of 1-year logMAR VA in regression models for both extracapsular (P = 0.0004, R2 = 0.45) and phacoemulsification groups (P < 0.00005, R2 = 0.46).\n Phacoemulsification is associated with better postoperative VA, less postoperative inflammation, and less need for capsulotomy than extracapsular cataract surgery in patients with diabetes. However, with both techniques, the principal determinant of postoperative VA appears to be the presence or absence of CSME at the time of surgery. Early intervention, reducing the risk that unrecognized CSME is present at the time of surgery, may be more critical to outcome than choice of surgical technique." ]

[ "1933160", "439971" ]

[ "Single-blind, randomised, parallel group study of the Bard Biocath catheter and a silicone elastomer coated catheter.", "[Clinical evaluation of Foley catheters]." ]

[ "A group of 69 community patients undergoing long-term urethral catheterisation for urinary incontinence took part in this study; 33 patients with a mean age of 70.03 years (+/- 16.6) received the Dow Corning Silastic catheter (16 F 10-ml balloon) and 36 patients with a mean age of 75.61 years (+/- 12.6) received the Bard Biocath catheter (16 F 10-ml balloon). Over a 16-week period catheters were monitored every 2 weeks and changed as necessary. The Bard Biocath catheter remained in situ for an average of 89.61 days (+/- 35.31) and the Silastic catheter remained in situ for an average of 56.7 days (+/- 38.8); this difference was statistically significant. Used catheters were analysed for encrustation using scanning electron microscopy (SEM). The average time in situ for non-encrusted Biocath catheters was 83.7 days and 25.28 days for non-encrusted Silastic catheters. It was found that 70% of patients who received Biocath catheters preferred them to their previous catheters whereas only 30% of patients in the Silastic group preferred the trial catheter. The incidence of bypassing was 28% in the Biocath group and 52.8% in the Silastic group.", "nan" ]

[ "18977178", "18541884", "21087403", "20655809", "20937130", "22067661" ]

[ "NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study.", "Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy.", "A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.", "A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.", "Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia.", "A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy." ]

[ "The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN.\n In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 microg/cm(2) [8% capsaicin]) or a low-concentration capsaicin control patch (3.2 microg/cm(2) [0.04% capsaicin]). Patients were aged 18-90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00115310.\n Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were -29.6%vs -19.9% (difference -9.7%, 95% CI -15.47 to -3.95; p=0.001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1.56, 95% CI 1.03 to 2.37; p=0.03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score -29.9%vs -20.4%, difference -9.5, -15.39 to -3.61; p=0.002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls.\n One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain.", "HIV-associated distal sensory polyneuropathy (HIV-DSP) is a painful condition with limited effective treatment. Capsaicin desensitizes cutaneous nociceptors resulting in reduced pain. We report a placebo-controlled study of a high-concentration capsaicin dermal patch (NGX-4010) for the treatment of painful HIV-DSP.\n This double-blind multicenter study randomized 307 patients with painful HIV-DSP to receive NGX-4010 or control, a low-concentration capsaicin patch. After application of a topical anesthetic, NGX-4010 or control was applied once for 30, 60, or 90 minutes to painful areas on the feet. The primary efficacy endpoint was percent change in Numeric Pain Rating Scale (NPRS) from baseline in mean \"average pain for past 24 hours\" scores from weeks 2 to 12.\n A single NGX-4010 application resulted in a mean pain reduction of 22.8% during weeks 2 to 12 as compared to a 10.7% reduction for controls (p = 0.0026). Following a transient treatment-related pain increase, pain was reduced; significant improvement was apparent by week 2 and continued throughout the controlled 12-week observation period. Mean pain reductions in the NGX-4010 30-, 60- and 90-minute groups were 27.7%, 15.9%, and 24.7% (p = 0.0007, 0.287, and 0.0046 vs control). One third of NGX-4010-treated patients reported >or=30% pain decrease from baseline as compared to 18% of controls (p = 0.0092). Self-limited, mild-to-moderate local skin reactions were commonly observed.\n A single NGX-4010 application was safe and provided at least 12 weeks of pain reduction in patients with HIV-associated distal sensory polyneuropathy. These results suggest that NGX-4010 could provide a promising new treatment for painful HIV neuropathy.", "To confirm the efficacy, tolerability, and safety of NGX-4010, an 8% capsaicin dermal patch (capsaicin 640 µg/cm(2) ), in patients with postherpetic neuralgia (PHN). PHN is a chronic pain disorder that can be difficult to treat and for which current treatment options are often limited by poor tolerability.\n A total of 418 patients were randomized to receive a single 60-minute application of NGX-4010 or a 0.04% capsaicin control patch (3.2 µg/cm(2) ) in a multicenter, double-blind, confirmatory, phase 3 study.\n Patients were 18-90 years old with a diagnosis of PHN, pain for at least 6 months, and an average baseline Numeric Pain Rating Scale (NPRS) score of 3-9.\n The primary efficacy end point was the percentage change in NPRS score from baseline to weeks 2-8.\n NGX-4010 recipients had a significantly greater mean reduction from baseline in pain during weeks 2-8 compared with the control group (32.0% vs 24.4%; P=0.011). A ≥ 30% reduction in mean NPRS scores was achieved in 46% of NGX-4010 recipients compared with 34% of controls (P=0.02). Pain was significantly lower in NGX-4010 recipients than controls by week 2, and greater pain reduction was maintained throughout the remaining 12-week study period. Most treatment-emergent adverse events were application site specific (notably erythema and pain), transient, and generally mild to moderate in severity.\n In patients with PHN, a single 60-minute application of NGX-4010 produced significant reduction in pain that was maintained over a 12-week period.\n Wiley Periodicals, Inc.", "Postherpetic neuralgia (PHN) is a painful complication of acute herpes zoster. This multicenter, double-blind, controlled study randomized 299 PHN patients to receive either NGX-4010, a high-concentration capsaicin (8%) patch, or a low-concentration capsaicin (0.04%) control patch for 30, 60, or 90 minutes. The mean percent reductions in NPRS score from baseline to weeks 2 through 8 were significantly greater in the total NGX-4010 group (26.5%, P = .0286) and the 90-minute NGX-4010 group (27.8%, P = .0438) compared to the pooled control group (17.3%). After review of the data suggested a difference between genders in reporting of pain scores and a higher proportion of males (61%) in the 60-minute NGX-4010 group, post hoc gender-stratified analyses were performed and showed that the 60-minute NGX-4010 group also had a significantly larger mean percent reduction in average pain scores (28.0%, P = .0331). Pain reduction in the 30-minute NGX-4010 group, although similar in magnitude to the other doses, was not significantly different from control in either of these analyses. Similar results were observed during weeks 2 through 12. Most treatment-emergent adverse events were application-site specific, transient and mostly mild to moderate in severity.\n This article reports the safety and efficacy of NGX-4010 applied for 3 different durations (30, 60, or 90 minutes) in patients with PHN. The results identified the 60-minute duration as the dose to be evaluated in subsequent studies and identified a gender effect on reported changes in pain.\n Copyright © 2010. Published by Elsevier Inc.", "Postherpetic neuralgia (PHN) is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN.\n This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS) score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8.\n The mean percent reduction in \"average pain for the past 24 hours\" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5%) compared with control (29.9%) although the difference was not significant (p = 0.296). PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much) compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in \"average pain for the past 24 hours\" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291). PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;).\n Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN, may have confounded the results of the prespecified analyses, and should be taken into account when designing PHN studies.\n NCT00068081.", "Effective treatment of HIV-associated distal sensory polyneuropathy remains a significant unmet therapeutic need.\n In this randomized, double-blind, controlled study, patients with pain due to HIV-associated distal sensory polyneuropathy received a single 30-minute or 60-minute application of NGX-4010--a capsaicin 8% patch (n = 332)--or a low-dose capsaicin (0.04%) control patch (n = 162). The primary endpoint was the mean percent change from baseline in Numeric Pain Rating Scale score to weeks 2-12. Secondary endpoints included patient global impression of change at week 12.\n Pain reduction was not significantly different between the total NGX-4010 group (-29.5%) and the total control group (-24.5%; P = 0.097). Greater pain reduction in the 60-minute (-30.0%) versus the 30-minute control group (-19.1%) prevented intended pooling of the control groups to test individual NGX-4010 treatment groups. No significant pain reduction was observed for the 30-minute NGX-4010 group compared with 30-minute control (-26.2% vs.-19.1%, respectively, P = 0.103). Pain reductions in the 60-minute NGX-4010 and control groups were comparable (-32.8% vs. -30.0%, respectively; P = 0.488). Posthoc nonparametric testing demonstrated significant differences favoring the total (P = 0.044) and 30-minute NGX-4010 groups (P = 0.035). Significantly, more patients in the total and 30-minute NGX-4010 group felt improved on the patient global impression of change versus control (67% vs. 55%, P = 0.011 and 65% vs. 45%, P = 0.006, respectively). Mild to moderate transient application site pain and erythema were the most common adverse events.\n Although the primary endpoint analyses were not significant, trends toward pain improvement were observed after a single 30-minute NGX-4010 treatment." ]

[ "16241873", "19538239", "18473689", "20714820", "17175680", "12649049", "15616230", "11140073", "8900703", "3533475", "12881874", "18227359", "20299481", "21788632", "21270188" ]

[ "A randomized, controlled trial of an automated wireless messaging system for diabetes.", "A Ubiquitous Chronic Disease Care system using cellular phones and the internet.", "WellDoc mobile diabetes management randomized controlled trial: change in clinical and behavioral outcomes and patient and physician satisfaction.", "Outcomes of minimal and moderate support versions of an internet-based diabetes self-management support program.", "Effects of a brief computer-assisted diabetes self-management intervention on dietary, biological and quality-of-life outcomes.", "The D-Net diabetes self-management program: long-term implementation, outcomes, and generalization results.", "Randomized effectiveness trial of a computer-assisted intervention to improve diabetes care.", "Telecommunication support for rural women with diabetes.", "The development and evaluation of a computer-aided diabetes education program.", "Effect of computer-based learning on diabetes knowledge and control.", "[Computer assisted nutrition therapy for patients with type 2 diabetes].", "Clinic-based support to help overweight patients with type 2 diabetes increase physical activity and lose weight.", "Online diabetes self-management program: a randomized study.", "Cluster-randomized trial of a mobile phone personalized behavioral intervention for blood glucose control.", "Improved glycemic control without hypoglycemia in elderly diabetic patients using the ubiquitous healthcare service, a new medical information system." ]

[ "Aggressive management of blood glucose reduces future diabetes-related complications, but this is difficult to achieve.\n This randomized, controlled study tested the effect of using a wireless two-way pager-based automated messaging system to improve diabetes control through facilitated self-management. The system sent health-related messages to patients, with automatic forwarding of urgent patient responses to the health care team.\n Participants in both the experimental (pager) and the control groups experienced an average hemoglobin A1c decrease of 0.1-0.3%. More patients in the pager group were normotensive, and more felt that their health care was better by the end of the study. A total of 79% of participants enjoyed using the pager, and 68% wanted to continue using the system.\n Utilizing a wireless, automated messaging system in clinical practice is a feasible, low-cost, interactive way to facilitate diabetes self-management, which is acceptable to patients. While providing a convenient way for patients and providers to communicate, this system can support automated recording and ready retrieval of these real-time interactions.", "The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide. To improve the quality and efficiency of chronic disease care, we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care (UCDC) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension.\n We conducted a randomized, controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre.\n After 12 weeks, there were significant improvements in HbA(1c) in the intervention group (7.6 +/- 0.9% to 7.1 +/- 0.8%, P < 0.001) compared with the control group (7.4 +/- 0.9% to 7.6 +/- 1.0%, P = 0.03). Furthermore, we observed a significant reduction in systolic and diastolic blood pressure, as well as improvements in total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels in the intervention group. Furthermore, there was a significant increase in adiponectin levels in the intervention group compared with the control group, although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group.\n The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension.", "Less than 63% of individuals with diabetes meet professional guidelines target of hemoglobin A1c <7.0%, and only 7% meet combined glycemic, lipid, and blood pressure goals. The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools. Secondary aims examined health care provider (HCP) adherence to prescribing guidelines and assessed HCPs' adoption of the technology.\n Thirty patients with type 2 diabetes were recruited from three community physician practices for a 3-month study and evenly randomized. The intervention group received cell phone-based software designed by endocrinologists and CDEs (WellDoc Communications, Inc., Baltimore, MD). The software provided real-time feedback on patients' blood glucose levels, displayed patients' medication regimens, incorporated hypo- and hyperglycemia treatment algorithms, and requested additional data needed to evaluate diabetes management. Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms. The system sent computer-generated logbooks (with suggested treatment plans) to intervention patients' HCPs.\n The average decrease in A1c for intervention patients was 2.03%, compared to 0.68% (P < 0.02, one-tailed) for control patients. Of the intervention patients, 84% had medications titrated or changed by their HCP compared to controls (23%, P = 0.002). Intervention patients' HCPs reported the system facilitated treatment decisions, provided organized data, and reduced logbook review time.\n Adults with type 2 diabetes using WellDoc's software achieved statistically significant improvements in A1c. HCP and patient satisfaction with the system was clinically and statistically significant.", "Internet and other interactive technology-based programs offer great potential for practical, effective, and cost-efficient diabetes self-management (DSM) programs capable of reaching large numbers of patients. This study evaluated minimal and moderate support versions of an Internet-based diabetes self-management program, compared to an enhanced usual care condition.\n A three-arm practical randomized trial was conducted to evaluate minimal contact and moderate contact versions of an Internet-based diabetes self-management program, offered in English and Spanish, compared to enhanced usual care. A heterogeneous sample of 463 type 2 patients was randomized and 82.5% completed a 4-month follow-up. Primary outcomes were behavior changes in healthy eating, physical activity, and medication taking. Secondary outcomes included hemoglobin A1c, body mass index, lipids, and blood pressure.\n The Internet-based intervention produced significantly greater improvements than the enhanced usual care condition on three of four behavioral outcomes (effect sizes [d] for healthy eating = 0.32; fat intake = 0.28; physical activity= 0.19) in both intent-to-treat and complete-cases analyses. These changes did not translate into differential improvements in biological outcomes during the 4-month study period. Added contact did not further enhance outcomes beyond the minimal contact intervention.\n The Internet intervention meets several of the RE-AIM criteria for potential public health impact, including reaching a large number of persons, and being practical, feasible, and engaging for participants, but with mixed effectiveness in improving outcomes, and consistent results across different subgroups. Additional research is needed to evaluate longer-term outcomes, enhance effectiveness and cost-effectiveness, and understand the linkages between intervention processes and outcomes.", "There is a need for practical, efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss. The objective of this study was to evaluate such a computer-assisted intervention.\n Type 2 diabetes primary care patients (n=335) from fee-for-service and health maintenance organization settings were randomized to social cognitive theory-based tailored self-management (TSM) or computer-aided enhanced usual care (UC). Intervention consisted of computer-assisted self-management assessment and feedback, tailored goal-setting, barrier identification, and problem-solving, followed by health counsellor interaction and follow-up calls. Outcomes were changes in dietary behaviours (fat and fruit/vegetable intake), haemoglobin Alc (HbA1c), lipids, weight, quality of life, and depression.\n TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up. Among patients having elevated levels of HbA1c, lipids or depression at baseline, there were consistent directional trends favouring intervention, but these differences did not reach significance. The intervention proved feasible and was implemented successfully by a variety of staff.\n This relatively low-intensity intervention appealed to a large, generally representative sample of patients, was well implemented, and produced improvement in targeted behaviours. Implications of this practical clinical trial for dissemination are discussed.", "A prerequisite to translating research findings into practice is information on consistency of implementation, maintenance of results, and generalization of effects. This follow-up report is one of the few experimental studies to provide such information on Internet-based health education.\n We present follow-up data 10 months following randomization on the \"Diabetes Network (D-Net)\" Internet-based self-management project, a randomized trial evaluating the incremental effects of adding (1) tailored self-management training or (2) peer support components to a basic Internet-based, information-focused comparison intervention. Participants were 320 adult type 2 diabetes patients from participating primary care offices, mean age 59 (SD = 9.2), who were relatively novice Internet users.\n All intervention components were consistently implemented by staff, but participant website usage decreased over time. All conditions were significantly improved from baseline on behavioral, psychosocial, and some biological outcomes; and there were few differences between conditions. Results were robust across on-line coaches, patient characteristics, and participating clinics.\n The basic D-Net intervention was implemented well and improvements were observed across a variety of patients, interventionists, and clinics. There were, however, difficulties in maintaining usage over time and additions of tailored self-management and peer support components generally did not significantly improve results.", "There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care settings. This report presents 12-month follow-up results from a computer-assisted, patient-centered intervention to improve the level of recommended services patients received from a variety of primary care settings.\n A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program. Physicians were stratified and randomized to intervention or control conditions and evaluated on two primary outcomes: number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program (PRP). Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale, lipid and HbA1c levels, and the Patient Health Questionnaire-9 depression scale.\n The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition. There was overall improvement on secondary outcomes of lipids, HbA1c, quality of life, and depression scores; between-condition differences were not significant.\n Staff in small, mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care. Alternative explanations for why these process improvements did not lead to improved outcomes, and suggested directions for future research are discussed.", "The Women to Women Diabetes Project tested the use of telecommunication technology to deliver diabetes education and social support to rural women with diabetes. The aims were to (1) test the effects of the computer intervention in providing support, information, and education on selected outcomes, and (2) evaluate the women's attitudes toward and satisfaction with the intervention and the support provided.\n Thirty women were randomized into computer and noncomputer groups and participated for 10 months. For 5 months, one group participated in a self-help support and educational group via the computer; the other group continued to use their usual modes of support and communication. Psychosocial well-being scales were administered and attitudes were surveyed.\n Improving health and higher educational levels positively influenced measures of social support and quality of life. Women who were married or who reported greater support had higher scores on the Personal Resource Questionnaire. The women expressed positive effects of the computer-based support group on their lives.\n The intervention was enthusiastically accepted, and could be conducted effectively in isolated rural areas.", "This paper describes the development and evaluation of a computer-aided learning (CAL) program. The program was tested in a trial that involved 36 people with diabetes; 20 received CAL lessons in diabetes management and 16 attended conventional diabetes classes conducted by diabetes educators. When measurements taken before and three months after the education were compared, both groups showed significant improvement in their knowledge; the blood glucose levels of the CAL group were significantly lower but those of the conventional education group were higher. This means that the CAL program was as effective as conventional education in imparting knowledge but it was more likely to motivate people to control their glucose levels. The CAL program allows diabetes educators to spend less time on education in basic knowledge and to concentrate more on motivational and social factors that are important determinants of patient compliance. It can also benefit people with diabetes whose access to health professionals and/or conventional diabetes education is restricted.", "Two interactive computer-based systems have been evaluated: a teaching program with text and animated graphics and a multiple-choice knowledge-assessment program (KAP) with optional prescriptive feedback. One hundred seventy-four routine-attending insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients were allocated to active and control groups to determine the effect of these programs on knowledge and control after a 4- to 6-mo follow-up period. Interactive computer teaching (ICT) resulted in a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), together with a mean fall of 0.8 and 0.7%, respectively, in HbA1c (P less than .05 and P greater than .1), but no changes were observed in respective control groups. The KAP with feedback also produced a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), of similar magnitude to the ICT program, and a mean fall in HbA1c of 1.2 and 1.3%, respectively (P less than .05), with no changes in the corresponding control groups. Even when KAP was used without prescriptive feedback, smaller but significant mean falls in HbA1c of 0.7 and 0.8% (P less than .05) were seen in IDDM and NIDDM patients, respectively, suggesting a motivational effect resulting from program participation.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the efficacy of the\" Diabetes Diet Advisor\"(PC-DR vision 1.0)\" for type 2 diabetes.\n One hundred and fifty type 2 diabetic patients were divided in the 2 groups. The study group included 88 type 2 diabetic patients managed by \"Diabetes Diet Advisor(PC-DR vision 1.0)\"; the control group included 62 cases with a fixed carbohydrate content. All patients were followed up for 8 weeks.\n After 8 weeks dietary therapy, the fasting blood glucose (FBG), cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL- C) and body mass index (BMI) in study group were all significantly less than those in the control group (P<0.05). In the study group,the significant decrease were achieved in all indicates and FBG and 2hPBG decreased persistently. Twenty-five patients (28.41%) in study group and 6 patients (9.68%) in control group reduced their dosage of hypoglycemic agents or stopped drug therapy (P=0.007).\n The software \"Diabetes Diet Advisor (PC-DR vision 1.0)\" is a useful tool of dietary management for patients with type 2 diabetes.", "Our objective was to test the effect of physicians providing brief health lifestyle counseling to patients with type 2 diabetes mellitus during usual care visits.\n We conducted a randomized controlled trial of a 12-month intervention at 2 large community health centers, enrolling 310 patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater. In the intervention group, self-management goals for nutrition and physical activity were set using a tailored computer program. Goals were then reviewed at each clinic visit by physicians. The control group received only printed health education materials. The main outcome measures included change in physical activity and body weight.\n In the intervention group, recommended levels of physical activity increased from 26% at baseline to 53% at 12 months (P< .001) compared with controls (30% to 37%; P= .27), and 32% of patients in the intervention group lost 6 or more pounds at 12 months compared with 18.9% of controls (odds ratio, 2.2; P= .006).\n A brief intervention to increase the dialogue between patients and health care providers about behavioral goals can lead to increased physical activity and weight loss.", "We hypothesized that people with type 2 diabetes in an online diabetes self-management program, compared with usual-care control subjects, would 1) demonstrate reduced A1C at 6 and 18 months, 2) have fewer symptoms, 3) demonstrate increased exercise, and 4) have improved self-efficacy and patient activation. In addition, participants randomized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement.\n A total of 761 participants were randomized to 1) the program, 2) the program with e-mail reinforcement, or 3) were usual-care control subjects (no treatment). This sample included 110 American Indians/Alaska Natives (AI/ANs). Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups.\n At 6 months, A1C, patient activation, and self-efficacy were improved for program participants compared with usual care control subjects (P < 0.05). There were no changes in other health or behavioral indicators. The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects. The subgroup with initial A1C >7% demonstrated stronger improvement in A1C (P = 0.01). At 18 months, self-efficacy and patient activation were improved for program participants. A1C was not measured. Reinforcement showed no improvement.\n An online diabetes self-management program is acceptable for people with type 2 diabetes. Although the results were mixed they suggest 1) that the program may have beneficial effects in reducing A1C, 2) AI/AN populations can be engaged in and benefit from online interventions, and 3) our follow-up reinforcement appeared to have no value.", "To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with standard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes.\n A cluster-randomized clinical trial, the Mobile Diabetes Intervention Study, randomly assigned 26 primary care practices to one of three stepped treatment groups or a control group (usual care). A total of 163 patients were enrolled and included in analysis. The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period. Secondary outcomes were changes in patient-reported diabetes symptoms, diabetes distress, depression, and other clinical (blood pressure) and laboratory (lipid) values. Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support. Patients received automated, real-time educational and behavioral messaging in response to individually analyzed blood glucose values, diabetes medications, and lifestyle behaviors communicated by mobile phone. Providers received quarterly reports summarizing patient's glycemic control, diabetes medication management, lifestyle behaviors, and evidence-based treatment options.\n The mean declines in glycated hemoglobin were 1.9% in the maximal treatment group and 0.7% in the usual care group, a difference of 1.2% (P < 0.001) over 12 months. Appreciable differences were not observed between groups for patient-reported diabetes distress, depression, diabetes symptoms, or blood pressure and lipid levels (all P > 0.05).\n The combination of behavioral mobile coaching with blood glucose data, lifestyle behaviors, and patient self-management data individually analyzed and presented with evidence-based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year.", "To improve quality and efficiency of care for elderly patients with type 2 diabetes, we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare (u-healthcare) service, which is an individualized health management system using advanced medical information technology.\n We conducted a 6-month randomized, controlled clinical trial involving 144 patients aged >60 years. Participants were randomly assigned to receive routine care (control, n = 48), to the self-monitored blood glucose (SMBG, n = 47) group, or to the u-healthcare group (n = 49). The primary end point was the proportion of patients achieving A1C <7% without hypoglycemia at 6 months. U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient's mobile phone. Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server. Once the data are transferred to the server, an automated system, the CDSS rule engine, generates and sends patient-specific messages by mobile phone.\n After 6 months of follow-up, the mean A1C level was significantly decreased from 7.8 ± 1.3% to 7.4 ± 1.0% (P < 0.001) in the u-healthcare group and from 7.9 ± 1.0% to 7.7 ± 1.0% (P = 0.020) in the SMBG group, compared with 7.9 ± 0.8% to 7.8 ± 1.0% (P = 0.274) in the control group. The proportion of patients with A1C <7% without hypoglycemia was 30.6% in the u-healthcare group, 23.4% in the SMBG group (23.4%), and 14.0% in the control group (P < 0.05).\n The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients." ]

[ "8937535", "8112232", "8505632", "1821833", "8453943", "10563619", "2127016", "2498073", "17938371", "2612495", "18077797", "8232944" ]

[ "Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures.", "Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial.", "Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures.", "Neuropsychological assessment in lamotrigine treated epileptic patients.", "Outcomes of add-on treatment with lamotrigine in partial epilepsy.", "A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial Seizure Study Group.", "A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures.", "Controlled trial of lamotrigine (Lamictal) for refractory partial seizures.", "Lamotrigine extended-release as adjunctive therapy for partial seizures.", "Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy.", "Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months.", "Placebo-controlled study of the efficacy and safety of lamotrigine in patients with partial seizures. U.S. Lamotrigine Protocol 0.5 Clinical Trial Group." ]

[ "The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.", "The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients.", "The results of a multicentre, randomised, double-blind, placebo controlled, crossover trial of lamotrigine as add-on therapy in patients with partial seizures poorly controlled by established antiepileptic drugs (AEDs) are presented. The study consisted of two 12 week treatment periods each followed by a four week washout period. During the lamotrigine treatment phase, patients received 150 mg or 300 mg daily dose depending on their concomitant AEDs to achieve concentrations in the range 1-3 mg/L. Forty one patients were entered at four centres and all patients entered completed the study. There was a highly significant (p < 0.001) decrease in total seizure counts on lamotrigine compared with placebo. Overall, 22% of patients experienced at least a 50% reduction in the total numbers of all seizures types on lamotrigine, compared with none on placebo. When the total numbers of partial seizures (simple and complex partial) were analysed there was also a significant (p < 0.05) reduction in seizure counts on lamotrigine compared with placebo. When total numbers of secondarily generalised seizures were compared the trend for a reduction in this seizure type did not achieve significance (0.05 < p < 0.1). Concomitant AED plasma concentrations were virtually unchanged. It is concluded that lamotrigine is an effective AED in the treatment of therapy-resistant partial seizures.", "A double-blind, placebo controlled cross over study assessed the efficacy of lamotrigine as adjunct therapy for patients with refractory partial seizures. In addition to the main study, a neuropsychological component evaluated three main areas of cognitive function. These included: i) Concentration and attention; ii) General Cerebral Efficiency, and iii) Mnestic functions--immediate, short term and new learning ability. Ten subjects (4 males, 6 females, age range 22 to 53, mean age 31.3 years) were involved in the study, each assessed 3 times--baseline, end of phase I and end of phase II. Whilst statistical analysis proved impracticable due to differing scores across cells, between the results of lamotrigine and placebo, clinically, there appeared to be a marginal reduction in General Cerebral Efficiency during the lamotrigine phase. In the light of these tests, the conclusion is advanced that lamotrigine does not specifically impair cognitive function, and that it does not impair mnestic function. An alternate hypothesis of interaction effects is posited for the slight reduction in speed of information processing.", "The need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health-related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, and mastery and a specifically designed seizure severity scale with patient- and caregiver-based components. This HRQL model was used in a randomized, placebo-controlled, double-blind, cross-over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic-clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple-regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs.", "To compare the safety and efficacy of add-on lamotrigine and placebo in the treatment of children and adolescents with partial seizures.\n Add-on and monotherapy lamotrigine is safe and effective in adults with partial seizures, and reports of preliminary uncontrolled trials suggest similar benefits in children.\n We studied 201 children with diagnoses of partial seizures of any subtype currently receiving stable conventional regimens of antiepileptic therapy at 40 study sites in the United States and France. After a baseline observation period (to confirm that more than four seizures occurred in each of two consecutive 4-week periods), patients were randomized to add-on lamotrigine or placebo therapy. A 6-week dose-escalation period was followed by a 12-week maintenance period.\n Compared with placebo, lamotrigine significantly reduced the frequency of all partial seizures and the frequency of secondarily generalized partial seizures in these treatment-resistant patients. The most commonly reported adverse events in the lamotrigine-treated patients were vomiting, somnolence, and infection; the frequency of these and other adverse events was similar to that in the placebo-treated group, with the exception of ataxia, dizziness, tremor, and nausea, which were more frequent in the lamotrigine-treated group. The frequency of withdrawals for adverse events was similar between groups. Two patients were hospitalized for skin rash, which resolved after discontinuation of lamotrigine therapy.\n Lamotrigine was effective for the adjunctive treatment of partial seizures in children and demonstrated an acceptable safety profile.", "Efficacy and safety of lamotrigine (LTG) as add-on therapy was assessed in a randomised double-blind placebo-controlled trial of this drug in 23 adult patients with refractory partial seizures. Fifteen patients showed an improvement on LTG treatment, with a greater than 50% decrease in total seizure count in 7 patients. Fourteen patients experienced fewer simple and complex partial seizures, with 8 patients benefitting by more than a 50% decrease in seizure frequency. The drug was well tolerated over the 2 month treatment period. The plasma concentration of concomitant antiepileptic drugs remained unchanged. No haematological or chemical abnormalities were noted.", "The antiepileptic effect of lamotrigine (LTG) was assessed in a double-blind, placebo-controlled crossover trial in 24 adult patients with refractory partial seizures. LTG or placebo was added to existing antiepileptic drugs (AEDs). The dose of LTG varied from 75 to 400 mg daily. Three patients did not complete the trial. One was withdrawn from the trial with ataxia, tiredness, dyspnea, and diplopia while receiving LTG and died 18 days later of invasive carcinoma involving the liver. A second patient was withdrawn during baseline for contravening admission criteria, and a third received LTG in error during both treatment periods. Twenty-one patients (12 men and 9 women) completed the trial. An analysis of seizure counts in the 12-week treatment period with LTG showed a statistically significant reduction in seizures as compared with placebo for total seizures (p less than 0.002), partial seizures (p less than 0.002), and secondarily generalized seizures (p less than 0.05). The analysis of total seizure days showed a significant reduction during LTG treatment (p less than 0.002). There were no statistically significant changes in plasma concentrations of phenytoin (PHT), carbamazepine (CBZ), primidone (PRM), or phenobarbital (PB) between the two treatment periods. The most common adverse events reported during the trial were diplopia, drowsiness, tiredness, ataxia, and headache, but although these were more frequent during LTG treatment, the differences from placebo were not statistically significant. No hematological or biochemical changes were noted.", "To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy.\n Patients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained.\n Of the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint-entire 19-week treatment phase: 46.6% vs 24.5%, p = 0.0001 [corrected] via Wilcoxon test; escalation phase: 29.8% vs 15.6%, p = 0.027; maintenance phase: 58.4% vs 26.8%, p [corrected] < 0.0001). The percentage of patients with >or=50% reduction in partial seizure frequency (44.0% vs 20.8%, p = 0.0002) [corrected] and time to >or=50% reduction in partial seizure frequency (p = 0.0001) [corrected] also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 16%, placebo 18%) [corrected] and dizziness (lamotrigine XR 19%, [corrected] placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant.\n Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation.", "A double-blind, placebo-controlled trial is reported of lamotrigine as add-on treatment in therapy-resistant epilepsy. A within-patients serial design was used, with two 3-month treatment periods and an intervening 6-week washout/crossover period. An unblinded investigator adjusted lamotrigine dosage to achieve a plasma concentration within a previously predicted therapeutic range. All patients had therapy-resistant partial seizures, some in combination with other seizure types and were without serious neurological or intellectual deficit. Of 34 patients recruited only one was withdrawn because of an adverse experience (maculo-papular rash) probably related to the experimental drug and 30 completed the trial. The other 3 withdrawals were due to default during baseline, dispensing error and cholecystectomy. There was a modest statistically significant reduction in total and partial seizures on lamotrigine compared to placebo treatment. There was no difference in adverse experiences or abnormal biochemical or haematological findings between the lamotrigine and placebo periods. The plasma concentrations of concomitantly administered antiepileptic drugs were not affected by lamotrigine treatment. It is concluded that lamotrigine shows promise as an antiepileptic drug with low toxicity.", "This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months.\n The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained.\n The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients.\n Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.", "We evaluated the efficacy and safety of lamotrigine (300 and 500 mg/day) as add-on therapy in a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of 216 patients with refractory partial seizures. During 6 months of treatment, median seizure frequency decreased by 8% with placebo, 20% with 300 mg lamotrigine, and 36% with 500 mg lamotrigine. Seizure frequency decreased by > or = 50% in one-third of the 500-mg group and one-fifth of the 300-mg group. Reductions in seizure frequency and seizure days were statistically significant, compared with placebo, for the 500-mg group but not the 300-mg group. Most adverse events were minor and resolved over time. Nine percent of patients on lamotrigine withdrew because of adverse experiences. Lamotrigine plasma concentrations appeared to be a linear function of dose, and the drug did not affect plasma concentrations of concomitant antiepileptic drugs. Lamotrigine was safe, effective, and well tolerated as add-on therapy for refractory partial seizures." ]

[ "16547328", "9950598", "15019322" ]

[ "Randomised controlled trial of topical ciclosporin A in steroid dependent allergic conjunctivitis.", "The immunomodulatory effect of topical cyclosporin A in atopic keratoconjunctivitis.", "A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis." ]

[ "To evaluate the efficacy, safety, and therapeutic effect of topical ciclosporin A 0.05% as a steroid sparing agent in steroid dependent allergic conjunctivitis.\n Prospective, randomised, double masked, placebo controlled trial comparing signs, symptoms, and the ability to reduce or stop concurrent steroid in steroid dependent atopic keratoconjunctivitis and vernal keratoconjunctivitis using 0.05% topical ciclosporin A compared to placebo. Steroid drop usage per week (drug score), symptoms, and clinical signs scores were the main outcome measures.\n The study included an enrolment of 40 patients, 18 with atopic keratoconjunctivitis and 22 with vernal keratoconjunctivitis. There was no statistical significant difference in drug score, symptoms, or clinical signs scores between the placebo and ciclosporin group at the end of the treatment period. No adverse reactions to any of the study formulations were encountered.\n Topical ciclosporin A 0.05% was not shown to be of any benefit over placebo as a steroid sparing agent in steroid dependent allergic eye disease.", "To perform a detailed examination of the immunomodulatory effects of topical cyclosporin A (CsA) in conjunctival tissue from patients with atopic keratoconjunctivitis (AKC).\n Patients with active AKC were randomly allocated into two groups of four patients. For 3 months one group received 2% CsA drops, and the other group received placebo drops. Superior tarsal conjunctival biopsy specimens were harvested before and after treatment and examined by one- and two-color immunohistochemistry to compare leukocyte counts, HLA-DR+ and IL-2R+ cell counts, HLA-DR positivity of conjunctival epithelial cells, and counts of T cells expressing the cytokines interleukin (IL)-2, IL-3, IL-4, IL-5, and interferon (IFN)-gamma.\n Posttreatment values were significantly less than pretreatment values for the total number of leukocytes and in the numbers of CD3+ T cells, CD4+ cells, CD8+ cells, CD20+ B cells, neutrophils, and macrophages, and there was a decrease in the CD4-CD8 ratio (P = 0.03) in the CsA group. There was a reduction from before CsA treatment to after CsA-treatment in the numbers of HLA-DR+ and IL-2R+ cells (P = 0.03), but the reduction in the epithelial cell HLA-DR expression did not reach significance. The number of T cells staining for IL-3 and IL-5 was reduced, although not to statistical significance, but there was a significant reduction in the number of T cells expressing IL-2 and IFN-gamma (P = 0.03) after CsA treatment compared with initial values. There were no statistically significant differences between pretreatment and posttreatment values in the placebo group. There was a clinical improvement in the CsA group and a clinical worsening in the placebo group.\n The in vitro effects of CsA translate into a reduction in T cells, a normalization of the CD4-CD8 ratio, a decrease in T-cell activation, and a reduction in T-cell cytokine expression, especially IL-2 and IFN-gamma. The decrease in HLA-DR expression may be mediated by the change in IFN-gamma. There were fewer B cells but not fewer plasma cells after CsA and no change in IL-4 expression, suggesting minimal effects on type I hypersensitivity responses. There was no significant reduction in mast cell or eosinophil numbers, but direct effects of topical CsA on their function may play a role in the therapy of ocular allergic disease. These results show that the beneficial effects of topical CsA in AKC are accompanied by important changes in conjunctival immune cell profiles.", "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." ]

[ "7839936", "6377899", "1432827", "3940333", "3959016" ]

[ "Cervical ripening and induction of labour by breast stimulation.", "The use of breast stimulation to prevent postdate pregnancy.", "Evaluation of two methods employed for cervical ripening.", "Cervical ripening by breast stimulation.", "Induction of labor with an electric breast pump." ]

[ "The value of gentle, unilateral breast stimulation in the ripening of cervix and induction of labour was studied. Three hundred patients with uncomplicated term pregnancies, (38-42 weeks) were recruited into the study, consisting of three separate randomised double blind prospective trials. The first trial was to evaluate the effectiveness of breast stimulation in ripening the cervices of 200 term primigravid patients. There was a mean change of 3.90 +/- 2.39 points in cervical score among the study group compared to 0.50 +/- 0.67 among the control group. Thirty-three per cent of the study group went into labour when compared with 4% among the control group. In a second study of cross-over trial involving 78 of the original 200 patients, the study (ex-control) group had a mean change in cervical score of 3.84 +/- 2.24 when compared with the control (ex-study) group, (1.43 +/- 1.08). In a third study involving 100 multiparous patients, a mean change in cervical score of 2.74 +/- 1.16 was observed in the study group when compared with the control group, 0.92 +/- 1.07. Forty-six per cent of the patients went into labour compared with 12% in the control group. All findings were highly significant and there were no maternal or fetal side-effects. The study confirmed the efficacy of breast stimulation in cervical ripening and induction of labour.", "Postdate pregnancy is estimated to occur in 3% to 12% of all gestations. Morbidity and mortality rates associated with this common obstetric problem are higher than those with term gestation. The incidence of fetal distress, birth injury, meconium aspiration, congenital malformations, macrosomia, and oligohydramnios is also greater in postdate pregnancy. We prospectively evaluated breast self-stimulation to determine its effect on the incidence of postdate pregnancy. Two hundred low-risk patients at 39 weeks' gestation were randomly assigned to either a control group or a breast-stimulation group. Results showed that breast stimulation reduced the number of pregnancies managed as postdates from 17 per 100 (17%) to five per 100 (5%) (p less than 0.01), a 70% reduction. It is concluded that breast stimulation in postdates pregnancies can decrease significantly the number of patients that must be monitored by biochemical or biophysical means.", "The study evaluates breast stimulation and oxytocin infusion as methods for cervical ripening in patients where an obstetric indication for induction of labour exists. Forty patients with a Bishop score of 5 or 6 were randomly selected for either breast stimulation or oxytocin infusion. In a similar group of 20 cases, no method was employed. The Bishop score improved in 41.2% of cases where breast stimulation was used as compared to 75% where an oxytocin infusion was given. Three foetal deaths in the breast stimulation group brought the study to a stop after 17 cases. Cervical ripening with an oxytocin infusion drip appears to be a better method since infusion dosage can be precisely controlled making the technique more predictable and reliable. Though breast stimulation is effective in ripening the cervix, it may be used only in cases of intrauterine foetal death as it may otherwise adversely affect foetal outcome.", "The effect of breast stimulation on cervical ripening was studied. One hundred patients who had completed 38 weeks' gestation and had uncomplicated antenatal courses were recruited and divided into two groups: treatment and control. In the treatment group, gentle breast stimulation of alternate breasts was performed first for 1.5 hours under monitoring in the hospital and then for three hours daily for three days at home. No uterine hypertonus was detected. It was found that there was a significant change in the Bishop score of 3.96 +/- 1.34 points in the stimulated group as compared with the control group 1.04 +/- 1.03 points. After three days, a cross-over trial was performed with the extreatment group becoming the control and the excontrol group undergoing breast stimulation for the same period of time and under the same conditions. Again, the excontrol group was found to have a better mean cervical score (3.11 +/- 1.42 points) than the extreatment group (0.76 +/- 0.97 points) during breast stimulation. It is stressed that no uterine hypertonus was detected with gentle, unilateral breast stimulation, and there were no maternal or fetal complications as a result of this modality of cervical ripening.", "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." ]

[ "1493717", "6809421", "8899261", "3530633", "487808", "2887401", "761675", "16246660", "15105064", "3084167", "6811195", "15802410", "2491981", "2112079", "2510968", "10739510", "12878284", "913116", "12338635", "3098498", "12336988" ]

[ "Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T.", "Long-term intracervical contraception with a levonorgestrel device.", "A 12-month comparative clinical investigation of a levonorgestrel-releasing intracervical device situated in the uterine cavity or cervical canal.", "A comparative clinical trial of Copper T 220 C and Alza T IPCS 52 intrauterine devices in Thai women.", "A collaborative study of the progesterone intrauterine device (Progestasert). The World Health Organization Task Force on Methods for the Regulation of Implantation.", "Microdose intrauterine levonorgestrel for contraception. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on Intrauterine Devices for Fertility Regulation.", "Experience with two different medicated intrauterine devices: a comparative study of the Progestasert and Nova-T.", "A comparative study of the levonorgestrel-releasing intrauterine system Mirena versus the Copper T380A intrauterine device during lactation: breast-feeding performance, infant growth and infant development.", "Clinical performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women: a comparative study.", "Five years' experience with levonorgestrel-releasing IUDs.", "Puerperal insertion of a copper-releasing and a levonorgestrel-releasing intrauterine contraceptive device.", "Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial.", "Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD.", "Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant-2 implants in China.", "The effect of intrauterine devices, the stainless steel ring, the copper T220, and releasing levonorgestrel, on the bleeding profile and the morphological structure of the human endometrium--a comparative study of three IUDs. A morphometric study of 96 cases.", "The effect of low-dose 3-keto-desogestrel added to a copper-releasing intrauterine contraceptive device on menstrual blood loss: a double-blind, dose-finding, placebo-controlled study.", "Randomized comparison of levonorgestrel- and copper-releasing intrauterine systems immediately after abortion, with 5 years' follow-up.", "Comparative study of the progesterone t (65 microgram daily) and copper 7 iud.", "Comparison of T Cu 200 and Progestasert IUDs.", "Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device.", "Comparison between two IUDs: Progestasert and CuT 200." ]

[ "In a European randomized multicenter study, the efficacy and safety of an intrauterine contraceptive device releasing 20 microgram levonorgestrel/24 hours (LNG-IUD) have been evaluated and compared to the Nova-T. Because the LNG-IUD has a strongly suppressive effect on the endometrium and in some women affects ovarian function, the return to fertility after removal of the IUD was studied. Two-hundred-nine women (71 in the Nova-T and 138 in the LNG-IUD group), who had their IUDs removed because of planning pregnancy, were followed at least 24 months or until termination of pregnancy. For the Nova-T, the cumulative conception gross rate was 71.2/100 women after 12 months (79.7 after 24 months) and for the LNG-IUD 79.1 (86.6 after 24 months). The difference between the devices is not statistically significant, and in spite of the endometrial suppression during use of LNG-IUD, there is no delay of return to fertility and in both groups 96% of the pregnancies occurred during the first year after removal of the device. Eighty-four % of the pregnancies in the Nova-T group and eighty-six % in the LNG-IUD group ended in live births. The results suggest that the endometrium recovers quickly, normal ovulations are established and the fertility seems to be unaffected after use of an LNG-IUD.", "An intracervical levonorgestrel-releasing mini-T device was tried as contraceptive in 100 fertile multiparous women for 3 years. This device release about 10 micrograms/day. The results were compared with those of an intrauterine levonorgestrel device and copper-T-200 (Cu-T-200). The continuation rates of the three device did not reveal any significant differences at 1, 2 and 3 years. Incidence of unintended pregnancies and removals due to bleeding and pain was comparable to those of Cu-T-200 but higher than those of intrauterine levonorgestrel device. The number of days of bleeding and spotting for both levonorgestrel devices was significantly lower than those for Cu-T-200.", "A randomized study was performed in two clinics in order to compare the efficacy, safety and acceptability of a new model of a levonorgestrel-releasing intracervical device situated either in the cervical canal (group I) or in the uterine cavity (group II). Group I included 151 women (age 18-43) and group II, 147 women (age 19-43). The number of nulliparous women was 145. The total expulsion rate was 9.1%. The expulsion rate was lower among nulliparous women (4.8%) than among parous women (13.1%). There was also a significant difference in the expulsion rates between the two clinics. Two pregnancies occurred in both groups and two of these were ectopic, one in each group. The other two occurred after unnoticed expulsion. These figures give 12-month cumulative pregnancy rates of 1.3% and 1.4% in groups I and II, respectively. Total infection rate was 0.3%. The continuation rates were 82.1% in group I and 85.0% in group II after the first year. At three-month follow-up there were significantly fewer menstrual problems in group I than in group II (p = 0.0266). It is concluded that expulsion is still a problem with a small device but it may be diminished by intrauterine insertion and by selecting the users carefully.", "Two IUDs (Copper T 220 C and Alza T IPCS 52) were comparatively studied by randomized insertions in 200 Thai women who attended the Family Planning Clinic at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University. Point estimates of the pregnancy rate and rate of removal for bleeding and pain at 18 months were lower for the copper device than for the Alza T IPCS 52, but neither these nor any other pertinent event rates reached statistical significance. Study of the Alza device was halted before the completion of 2 years because reports from other centres indicated an unacceptable pregnancy rate beyond 2 years.", "A randomised double blind study of a plain T-shaped IUD and an active T-shaped IUD releasing 65 micrograms/day of progesterone, has been completed in four centres. A study of 1320 progesterone-releasing IUD's in parous women for 9660 women months of use significant to 18 months, gave a pregnancy rate of 1.0 +/- 0.4, expulsion of 4.7 +/- 0.6 and removals for pain and bleeding of 6.0 +/- 0.7. A detailed analysis of the menstrual bleeding patterns in these patients gave details of the number and length of bleeding and spotting episodes, count of bleeding days, and count of spotting episodes and days for four one-hundred-day reference periods. While the plain IUD contributed a significant number of intermenstrual spotting and bleeding days, the progesterone-releasing IUD contributed more spotting days.", "An intrauterine device (IUD) releasing 2 micrograms of levonorgestrel per 24 hours was compared in a randomized multicentre clinical trial with two copper IUDs-the TCu 220C and the Nova T. The 2 micrograms levonorgestrel device had statistically significantly higher pregnancy rates (from 390 days of use) and higher expulsion rates (up to 570 days). In addition, the total medical removals and removals for bleeding were significantly higher at all intervals where the data were analysed. Most disturbing was a 6.7 increased relative risk of ectopic pregnancy with the steroid-releasing IUD compared to the combined copper IUD data. It is concluded that the goal of microdose administration of 2 micrograms levonorgestrel to the uterine cavity does not achieve the objectives of a new and improved IUD device which is safe and effective.", "A comparative study of the Progestasert (UPS) and the Nova-T in 326 randomly selected women was carried out. The observation period was 1 year. The over-all continuation rates for the two types of intrauterine devices (IUDs) were similar. The expulsion rate for the Nova-T (9.2%) was considerably higher (P = 0.001) than that for the UPS (1.2%). Medical removals for bleeding/pain were more frequent (P = 0.028) for the UPS (15.4%) as compared with the Nova-T (6.1%). The pregnancy rate for the UPS (Pearl index = 4.8) was insignificantly higher than that for the Nova-T (Pearl index = 2.8). Two of the pregnancies in the UPS group were ectopic. No significant changes in the reactive immunoglobulins (IgA, IgG, or IgM) were observed in either of the groups. Our results indicate that neither of these two IUDs is preferable to the already existing medicated IUDs, such as the Copper T or the Copper 7.", "Mirena is a levonorgestrel-releasing intrauterine system (LNG-IUS) that provides highly effective and long-acting progestogen-only contraception.\n The objective of this study was to analyze the possible effects of using LNG-20 microg IUS on breast-feeding performance, infant growth and infant development during the first postpartum year as compared with the Copper T380A intrauterine device (Cu T380A IUD).\n This study is a prospective, controlled and randomized trial.\n The study was conducted at the Department of Obstetrics and Gynecology, Assiut University Hospital, Egypt.\n Three hundred twenty lactating women asking for initiation of contraception during the early postpartum stage were assigned randomly into two groups, the LNG-20 microg IUS group (n=163) and the Cu T380A group (n=157). The insertions were done 6-8 weeks postpartum. Each participant was followed up at three monthly intervals after insertion and until the first birthday of her baby. During these visits, the breast-feeding pattern was assessed, certain infant physical growth parameters were measured and a set of infant development tests was performed.\n No pregnancy occurred in both groups. There were no significant differences in the net continuation rates between the two groups (89.3 for LNG-IUS vs. 90.9 for Cu T380A). The LNG-20 microg IUS group had comparable rates of breast-feeding continuation, complete weaning, full breast-feeding and partial breast-feeding, with the Cu-IUD group. No statistically significant differences were found between groups with regard to all infant physical growth parameters and various infant development tests.\n The findings of the current study confirm that the use of LNG-20 microg IUS during the first postpartum year in lactating women provides highly effective and acceptable contraception and does not negatively influence breast-feeding or the growth and development of breast-fed infants.", "This 1-year randomized study was carried out at family-planning clinics of two university hospitals to compare the safety and acceptability of a levonorgestrel-releasing intrauterine system (LNG IUS) and oral contraceptives (OCs) in young nulliparous women. The study population consisted of 200 women aged 18-25 years seeking contraception. Ninety-four women entered the LNG IUS group and 99 entered the OC group. Continuation rates, reasons leading to discontinuation, adverse events, menstrual questionnaires, subjective well-being and sexual behavior were evaluated. Nineteen women (20%) in the LNG IUS group discontinued the study during the 1-year observation period, and 27 discontinued (27%) in the OC group. The most common reason (31%) for discontinuation in the IUS group was pain. In the OC group, hormonal side effects were the predominant medical reason for study termination. The safety and acceptability of the LNG IUS for contraception was observed to be as good as with OCs, with a high continuation rate.", "Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs.", "A copper-releasing IUD and levonorgestrel-releasing IUDs releasing 30 micrograms and 10 micrograms levonorgestrel per day were inserted six weeks after delivery in 110 volunteers. During the treatment, events and patterns of bleeding were recorded and plasma levonorgestrel concentrations were measured. The number of events in one year of follow-up was very low, four removals out of 40 in the copper-releasing IUD group and five removals out of 70 in the levonorgestrel-releasing IUD group. Bleeding and spotting was significantly more common after insertion of a levonorgestrel-releasing IUD than a copper-releasing IUD, but it was scanty and well-tolerated. After three months, levonorgestrel-releasing IUD patients had less bleeding and spotting than the copper-releasing IUD patients. No pregnancies occurred during the study period. There were two uterine perforations with a uterine sound at the insertion. In the 30-micrograms per day levonorgestrel-releasing IUD group, initially high plasma levonorgestrel concentrations reached a plateau four weeks after the insertion. In the 10-micrograms per day levonorgestrel-releasing IUD group, the plasma concentrations of levonorgestrel stabilized after the initial two weeks.", "Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women.\n We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well.\n Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months.\n The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized.\n I.", "A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.", "The levonorgestrel-releasing IUD (LNG-IUD, 20 micrograms/d) and the Norplant-2 implants were studied in a randomized comparative clinical trial with 200 women for one year. No pregnancy or expulsion occurred with the Norplant-2. In the LNG-IUD group, there was one pregnancy at the 12th month of use after an unnoticed expulsion. The net cumulative pregnancy and expulsion rates of LNG-IUD were 1.0 and 3.0. The removal rate due to menstrual disturbances in both LNG-IUD and Norplant-2 groups was 3.0. The use-related discontinuation rates were 9.0 and 3.0, and the continuation rates were 90.0 and 96.0, respectively. The differences were not statistically significant. Menstrual disturbance was the main side effect. It was improved after long time use, especially in the LNG-IUD group. After one year, the percentages of women with amenorrhea were 18.9 for the LNG-IUD and 8.3 for the Norplant-2. The menstrual blood loss was statistically significantly reduced in the LNG-IUD group, and blood haemoglobin concentration increased in both groups. The LNG-IUD and Norplant-2 are highly effective, safe, long-acting, and well accepted by the Chinese women.", "Thirty-four women using the stainless steel ring (SS), 43 women using the Copper T220 (TCu), and 19 women using levonorgestrel-releasing intrauterine devices (LNG) were admitted to the study. The light microscopic biopsy material was subjected to morphometric studies including 8 indices of endometrial activity before (Control) and after 24 months of exposure to the SS and TCu device and 3-10 months of exposure to the LNG device. The women were grouped into subjects with and without intermenstrual and prolonged bleeding. The results revealed that there were highly significant differences between the IUDs at the endometrial level as displayed by morphometry. However, the difference between bleeders and non-bleeders was not significant in any of the three types of IUDs. Although the mode of action of these IUDs at the endometrial level is different, the mechanism responsible for the irregular endometrial bleeding needs to be further investigated.", "We sought to establish the lowest dose of 3-keto-desogestrel, when added to a copper-releasing intrauterine contraceptive device, that is needed to reduce menstrual blood loss to a very low level and to treat (essential) menorrhagia successfully.\n A double-blind group comparative study was designed in which 203 healthy women with or without menorrhagia were enrolled and randomized to four different Multiload Cu250 intrauterine contraceptive devices, releasing 0 (control), 1.5, 3, or 6 microg of 3-keto-desogestrel daily. Menstrual blood loss, hemoglobin, and serum ferritin levels were determined before and during treatment.\n All 3-keto-desogestrel-copper intrauterine contraceptive devices reduced menstrual blood loss significantly, causing a reduction of up to 30 to 40 mL after 12 months of use. All women with essential menorrhagia were considered to have been successfully treated after 6 months of use. Serum ferritin levels rose with all three 3-keto-desogestrel-loaded devices.\n A Multiload Cu250 intrauterine contraceptive device releasing 1.5 microg of 3-keto-desogestrel daily is able to reduce menstrual blood loss to a very low level and to replete body iron stores in women with or without menorrhagia. Higher doses have no superior effect.", "Women who seek an abortion are motivated to use contraceptive methods afterwards. Because the return of fertility after abortion is immediate, there is a need for effective and safe contraception promptly after the termination of pregnancy. A randomized trial of Mirena and NovaT intrauterine contraceptive devices inserted at the time of elective termination of pregnancy, duration no more than 12 weeks, is reported here. Women were randomized 2:1 resulting in 305 subjects with Mirena and 133 with NovaT as a segment of a larger study of 3000 women. In the Mirena group, two pregnancies at year 4 resulted in a final gross rate of 0.8 at 5 years, which was significantly (p < 0.0004) lower than the corresponding rate of 9.5 with NovaT. Terminations because of expulsion, bleeding problems, pain, pelvic inflammatory disease and other medical reasons were less common in the Mirena group, but not significantly different. The cumulative expulsion gross rate for NovaT at 5 years was 15.4 and for Mirena it was 10.5. Termination rates because of amenorrhea were low in both groups. It is concluded that both devices were well tolerated. Mirena was more effective and the rate of adverse events was lower than with NovaT. Special attention should be paid to the insertion procedure when carried out at the time of abortion.", "nan", "Insertions of the T Cu 200 and the Progestasert IUDs in a total of 400 postpartum women were compared. Insertions were carried out within 10 minutes of delivery, either manually or with an inserter. There was a significant difference in the 6 and 12 month expulsion rates (P0.05) between the 2 groups, but no differences were found related to type of insertion. 12 month expulsion rates for the T Cu hand and inserter groups were 9.0 and 8.1, respectively, and 35.8 and 35.2 for the Progestasert hand and inserted groups, respectively. Overall, significantly fewer Progestasert users reported dysmenorrhea at follow-up and the specific 12 month dysmenorrhea rate was significantly lower for the Progestasert users than for the T Cu users. More women in the Progestasert groups reported intermenstrual spotting and bleeding, but specific 12 month rates of intermenstrual pain, spotting, and bleeding showed no differences between the groups.", "Following use of either the Levonorgestrel 20 mcg/day or the TCu 380 Ag IUD in a randomized comparative study, 110 women stopped contracepting to have planned pregnancies. Pregnancy rates and recovery of fertility have been assessed. Age at acceptance, duration of use, parity and intervals between last pregnancy and IUD insertion or removal were similar for both groups. Life table pregnancy rates at one year were higher than 90 per cent for both device groups; but because some women quickly changed their minds or had been at risk of pregnancy only a short time before the analysis date, only 60.9 percent had actually become pregnant. Median time to planned pregnancy was 3 months for the TCu 380 Ag group and 4 months for the Levonorgestrel 20 group. Neither duration of use nor age at insertion or age at termination affected the pregnancy rates significantly.", "nan" ]

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[ "ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group.", "Benefits of magnesium in acute myocardial infarction: timing is crucial.", "Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality.", "Magnesium substitution in acute ischaemic heart syndromes.", "Decreases by magnesium of QT dispersion and ventricular arrhythmias in patients with acute myocardial infarction.", "Protective effect of intravenous magnesium in acute myocardial infarction following thrombolytic therapy.", "Correlations between ventricular arrhythmias and electrolyte disturbances after acute myocardial infarction.", "Cardioprotective effects of magnesium sulfate in patients undergoing primary coronary angioplasty for acute myocardial infarction.", "A randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty.", "Threatening arrhythmias in acute myocardial infarction are prevented by intravenous magnesium sulfate.", "Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction.", "Adjunctive magnesium infusion therapy in acute myocardial infarction.", "[Intravenous magnesium in acute myocardial infarct].", "Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial.", "Beneficial effect of magnesium sulfate in acute myocardial infarction.", "Effects of intravenous magnesium sulphate in suspected acute myocardial infarction on acute arrhythmias and long-term outcome.", "Magnesium therapy in acute myocardial infarction--a double-blind study.", "Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy.", "Investigation of the effects of intravenous magnesium sulphate on cardiac rhythm in acute myocardial infarction.", "Comparison between nicorandil and magnesium as an adjunct cardioprotective agent to percutaneous coronary intervention in acute anterior myocardial infarction." ]

[ "58,050 patients entering 1086 hospitals up to 24 h (median 8 h) after the onset of suspected acute myocardial infarction (MI) with no clear contraindications to the study treatments (in particular, no cardiogenic shock or persistent severe hypotension) were randomised in a \"2 x 2 x 2 factorial\" study. The treatment comparisons were: (i) 1 month of oral captopril (6.25 mg initial dose titrated up to 50 mg twice daily) versus matching placebo; (ii) 1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo; and (iii) 24 h of intravenous magnesium sulphate (8 mmol initial bolus followed by 72 mmol) versus open control. There were no significant \"interactions\" between the effects of these three treatments, and the results for each are based on the randomised comparison of about 29,000 active versus 29,000 control allocated patients. Captopril There was a significant 7% (SD 3) proportional reduction in 5-week mortality (2088 [7.19%] captopril-allocated deaths vs 2231 [7.69%] placebo; 2p = 0.02), which corresponds to an absolute difference of 4.9 SD 2.2 fewer deaths per 1000 patients treated for 1 month. The absolute benefits appeared to be larger (perhaps about 10 fewer deaths per 1000) in certain higher-risk groups, such as those presenting with a history of previous MI or with heart failure. The survival advantage appeared to be maintained in the longer term (5.4 [SD 2.8] fewer deaths per 1000 at 12 months). Captopril was associated with an increase of 52 (SD 2) patients per 1000 in hypotension considered severe enough to require termination of study treatment, of 5 (SD 2) per 1000 in reported cardiogenic shock, and of 5 (SD 1) per 1000 in some degree of renal dysfunction. It produced no excess of deaths on days 0-1, even among patients with low blood pressure at entry. Mononitrate There was no significant reduction in 5-week mortality, either overall (2129 [7.34%] mononitrate-allocated deaths vs 2190 [7.54%] placebo) or in any subgroup examined (including those receiving short-term non-study intravenous or oral nitrates at entry). Further follow-up did not indicate any later survival advantage. The only significant side-effect of the mononitrate regimen studied was an increase of 15 (SD 2) per 1000 in hypotension. Those allocated active treatment had somewhat fewer deaths on days 0-1, which is reassuring a bout the safety of using nitrates early in acute MI.(ABSTRACT TRUNCATED AT 400 WORDS)", "To evaluate magnesium deficiency during and after acute myocardial infarction (AMI) and the role of intravenous magnesium therapy given in the early postinfarction period.\n One hundred patients with AMI were randomly assigned to 2 equal groups and monitored over a 4-week period. The placebo group received intravenous dextrose solution and the trial group was given 15 g intravenous magnesium (62 mmol) over a 48-hour period. Serum magnesium levels were measured on days 1, 2, 4, and 6 after admission by calorimetry with methyl thymol blue.\n The groups were comparable in prevalence of risk factors for coronary artery disease and other acute parameters of AMI. The serum magnesium levels of a group of 50 controls were higher (1.61 +/- 0. 21 vs 1.23 +/- 0.27mEq/L) than in patients with AMI (P <.001). There was an increase in serum magnesium levels in the trial group on day 2 (1.73 +/- 0.27 vs 1.29 +/- 0.28 mEq/L; P <.001) as well as on day 4 (1.62 +/- 0.25 vs 1.38 +/- 0.36 mEq/L; P <.001). The trial group also showed significantly lower incidence of arrhythmias (8% vs 34%) and death (4% vs 20%). The mortality rate from pump failure was reduced in the trial group (4% vs 14%).\n The serum magnesium levels in patients with AMI were lower compared with controls. The administration of intravenous magnesium to patients in the immediate postinfarction period is cardioprotective and decreases the incidence of arrhythmia, pump dysfunction, and death. Thus intravenous magnesium is a safe, effective, and inexpensive modality of treatment in AMI.", "Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study.", "It has recently been suggested that intravenous infusion of magnesium may reduce mortality and the incidence of serious arrhythmias in patients with ischaemic heart disease and acute myocardial infarction. In the present double-blind, placebo-controlled study, 298 patients with suspected acute myocardial infarction were randomized to receive either intravenous magnesium chloride (80 mmol.24 h-1) or placebo. Infusions were started immediately after admission to the coronary care unit. One hundred and fifty patients received magnesium and 148 the placebo. Ischaemic heart disease was diagnosed in 244 patients. Acute myocardial infarction was observed among 83 patients in the magnesium group and 79 in the placebo group. Both treatment groups were comparable regarding sex, age, clinical status, previous cardiac disease and medication. Serum magnesium was significantly raised during magnesium infusion compared to placebo (P less than 0.01). Fatal events were only observed among patients with myocardial infarction, but neither the in-hospital mortality (magnesium: 12.1%; placebo 10.1%) nor the mortality after a follow-up period of 245 days (median observation time) was affected by magnesium substitution. Magnesium infusion was accompanied by a significantly increased incidence of atrioventricular conduction disturbances. The results suggest that patients suffering from acute ischaemic heart syndromes do not benefit from intravenous magnesium supplementation.", "Magnesium treatment suppresses ventricular arrhythmias in acute myocardial infarction and possibly mortality after infarction, but the underlying mechanisms are inadequately understood. We tested whether the effect of magnesium could be attributed to an influence on the autonomic control of the heart, changes in disturbed repolarization, relief of ischaemia or limitation of myocardial injury.\n Fifty-nine consecutive patients with acute myocardial infarction were randomized to receive 70 mmol of magnesium (n = 31) infused over 24 h or placebo (n = 26). Occurrence of ventricular arrhythmias and heart rate variability (SD of 5-min mean sinus beat intervals over a 24 h period, SDANN; low frequency/high frequency amplitude ratio, LF/HF ratio), and the number of ischaemic episodes on vectorcardiography were measured from the first day of treatment. QT dispersion corrected for heart rate was measured from the 12-lead ECG. Magnesium decreased the number of hourly ventricular premature beats (P < 0.001) and the number of ventricular tachycardias (P < 0.05). QT dispersion corrected for heart rate was decreased in both measurements at 24 h and 1 week (P < 0.001). SDANN and LF/HF ratio were unchanged. The number of ischaemic episodes on vectorcardiography were equal, and peak creatine kinase MB release did not differ between the groups. In testing the pathophysiological mechanisms, serum magnesium levels after infusion correlated with hourly ventricular premature beats (rs = -0.47; P < 0.01), ventricular tachycardias (rs = -0.26; P < 0.05), and QT dispersion corrected for heart rate (rs = -0.75; P < 0.001), but not with SDANN, LF/HF ratio or peak creatine kinase MB. QT dispersion corrected for heart rate correlated with hourly ventricular premature beats (rs = 0.48; P < 0.001) and ventricular tachycardias (rs = 0.27; P < 0.05).\n Magnesium suppresses early ventricular arrhythmias in acute myocardial infarction. The decreased arrhythmicity is related to enhancement of homogeneity in repolarization, but not to attenuation of prevailing ischaemia, improvement of autonomic nervous derangements or myocardial salvage.", "The role of intravenous magnesium therapy in patients with acute myocardial infarction (AMI) who received thrombolytic therapy is controversial. The results from previous clinical trials were not in consonance. We therefore conducted a prospective, randomized, double-blind, placebo controlled study in 350 patients with confirmed AMI during the period January 1994 to December 1996. The role of intravenous magnesium sulphate therapy (2 g over 5 min followed by 16 g over 24 h) was evaluated in patients with AMI who received thrombolytic therapy. Study group consisted of 169 patients who were administered magnesium sulphate. Control group comprised of 181 patients who were given isotonic saline. Among those in the magnesium group, 70% received magnesium within 6 h after the onset of symptoms. All patients received magnesium immediately after the completion of thrombolytic therapy. Patients were followed up for 30 days after AMI. The number of deaths in the study group was 6 (3.5%) compared with control arm in which 18 patients (9.9%) died (P value <0.01 95% Confidence intervals [CI] 1.2 to 11.6). Ventricular arrhythmias were also less in the magnesium arm; 27 patients (13%) compared with 83 patients (48.6%) in the control arm (P value 0.00001 95% Cl 26.7 to 44.5). In the magnesium group 15 patients (8.8%) had re-infarction compared with 23 patients (12.7%) in the placebo arm (P value not significant). Post myocardial infarction angina was observed in 47 patients (27.8%) in the magnesium arm compared with 60 patients (33.1%) in the placebo arm (P value not significant). The main side effect of intravenous magnesium was transient flushing observed in 152 (90%) patients. Intravenous magnesium sulphate in patients with AMI is a safe and useful adjunct to thrombolytic therapy in reducing the short-term mortality and ventricular arrhythmias after AMI.", "Seven 24-hour ECG recordings and blood samples were taken within 3 weeks in 42 patients who had suffered an acute myocardial infarction (AMI). Ca, K and Mg concentrations in serum, and K and Mg in the erythrocytes, were determined by atomic absorption spectroscopy. One half of the patients were infused with 81 mval/day MgSO4 for 3 days. In patients who exhibited intense electrolyte alterations 10-20 days after AMI, there was a significantly higher rate in the frequency of couplets and/or tachycardia in the 2- to 20-day period after AMI. In patients infused with MgSO4, the fluctuation in serum electrolytes and the rate of arrhythmias were significantly reduced.", "Experimental evidence indicates that magnesium sulfate may have potential cardioprotective properties as an adjunct to coronary reperfusion. The present study was designed to examine the hypothesis that magnesium might have beneficial effects on left ventricular (LV) function and coronary microvascular function in patients with acute myocardial infarction (AMI).\n The study population of 180 consecutive patients with a first AMI (anterior or inferior) underwent successful primary coronary intervention. Patients were randomized to treatment with either intravenous magnesium (magnesium group, n=89) or normal saline (control group, n=91). Pre-discharge left ventriculograms were used to assess LV ejection fraction (LVEF), regional wall motion (RWM) within the infarct-zone and LV end-diastolic volume index. The Doppler guidewire was used to assess coronary flow velocity reserve (CFVR) as an index of coronary microvascular function. Magnesium group subjects showed significantly better LV systolic function (LVEF 63+/-9% vs 55+/-13%, p<0.001; RWM: -1.01+/-1.29 SD/chord vs -1.65+/-1.11 SD/chord, p=0.004), significantly smaller LV end-diastolic volume index (63+/-17 ml/m(2) vs 76+/-20 ml/m(2), p<0.001), and significantly higher CFVR (2.95+/-0.76 vs 2.50+/-0.99, p=0.023) than controls.\n Magnesium sulfate as an adjunct to primary coronary intervention shows favorable functional outcomes in patients with AMI.", "Notwithstanding the negative result of the International Study of Infarct Survival-4 (ISIS-4), the controversy about the role of magnesium in acute myocardial infarction is still open because, according to experimental data, magnesium could decrease myocardial damage and mortality only if infusion is started before reperfusion. This randomized placebo-controlled trial was designed to evaluate the effect of intravenous magnesium, delivered before, during, and after direct coronary angioplasty, in patients with acute myocardial infarction.\n One-hundred fifty patients were randomized to intravenous magnesium sulfate or placebo. The primary end point was an infarct zone wall motion score index at 30 days, as a measure of infarct size. The secondary end points included creatine kinase peak, ventricular fibrillation/tachycardia within the first 24 hours, death and congestive heart failure within the 30-day follow-up, and 30-day left ventricular ejection fraction. Analysis was by intention to treat.\n There were no significant differences between the magnesium and placebo groups in the 30-day infarct zone wall motion score index (1.93 +/- 0.61 vs 1.85 +/- 0.51, P =.39), ventricular arrhythmias (24% vs 15%, P =.15), death (0 vs 1%, P =.32), heart failure (8% vs 7%, P =.75), and 30-day left ventricular ejection fraction (49% +/- 11% vs 50% +/- 9%, P = 0.55). There was a trend toward a higher creatine kinase peak in the magnesium group (3059 +/- 2359 vs 2404 +/- 1673,P =.052).\n Intravenous magnesium delivered before, during, and after reperfusion did not decrease myocardial damage and did not improve the short-term clinical outcome in patients with acute myocardial infarction treated with direct angioplasty.", "nan", "Seven of 48 patients (14.6%) with acute myocardial infarction who were given 2.4 g of magnesium sulfate as a single intravenous dose had potentially lethal arrhythmias during the first 24 hours after admission, whereas 16 (34.8%) of 46 patients receiving placebo had similar arrhythmias. In addition, 14 of these 16 patients in the placebo group had their first arrhythmia (in the intensive coronary-care unit) within two hours after the start of the study, whereas in the magnesium-treated group, there were no such arrhythmias until some four hours later. The higher the lymphocyte potassium concentration, the greater the reduction in the incidence of arrhythmias. Serum magnesium levels increased by 16.5% and lymphocyte magnesium concentrations by 72% in the magnesium treated group. Intravenous magnesium reduces the incidence of serious arrhythmias after acute myocardial infarction.", "Intravenous magnesium therapy in acute myocardial infarction (MI) has been shown to be beneficial in many studies. However, these effects are not consistent from one trial to another, and their clinical significance is often questionable. A total of 78 consecutive patients were included in a prospective placebo controlled, randomized study of the effects of intravenous magnesium sulfate infusion in acute MI. Of these, 52 (66%) received intravenous streptokinase and the rest belonged to a non-thrombolysed group. These patients were randomized to receive magnesium sulfate infusion (8 mmol over 5 min followed by 65 mmol over 24 h) or placebo. The end points were serious arrhythmias, left ventricular ejection fraction (LVEF) and death during hospital stay and at the end of 28 days. LVEF measured by radionuclide ventriculography at discharge (9 +/- 5 days) was similar in two groups (41 +/- 11 vs. 39 +/- 10; magnesium vs. placebo respectively, P = 0.40). However, the LVEF of the placebo-treated thrombolysed group was higher than the non-thrombolysed group (42 +/- 10 vs. 37 +/- 0, P = 0.02). Incidence of nonsustained ventricular tachycardia (NSVT) was higher with placebo than with magnesium (50% vs. 23% respectively, P < 0.02, odds ratio = 0.29; 95% confidence intervals (CI) 0.1-0.85). Mortality during hospital stay and at the end of 28 days was also similar in both the groups. Thus, the administration of magnesium infusion as an adjunct to thrombolytic therapy remains to be of questionable benefit.", "The effects of magnesium (Mg) on the incidence of arrhythmias and on mortality were evaluated in 61 patients with documented acute myocardial infarction (AMI), in a randomized, double blind placebo controlled study. During the first 24 hours 31 patients received infusion of 1000 ml isotonic saline with 17 g MgSO4 and 30 ones received only equal volumes of saline as placebo. The baseline characteristics of the population including serum Mg and potassium were similar in the two groups. Severe arrhythmias were not as frequent in the Mg group (22%) as in the placebo one (36%), but the difference was not statistically significant (p = 0.05). There is no significant difference between the groups neither in mortality (3.2%; 0%) nor in conduction disturbances (3.2%; 3%). The adverse effects of Mg therapy were transient and therapy interruption was not required.\n Although the trial is not an extensive one, and the results are nonsignificant, we consider intravenous Mg therapy to be simple and cheap with its place in the treatment of AMI in properly selected patients. According to available data it should be administered as soon as possible after the onset of AMI symptoms, before thrombolytic therapy, in 24-hrs. dose not exceeding 50-65 mmol probably through several days, but the optimal duration of therapy should be further investigated.", "The benefits of supplemental administration of intravenous magnesium in patients with ST-elevation myocardial infarction (STEMI) are controversial. Despite promising results from work in animals and the ready availability of this simple, inexpensive treatment, conflicting results have been reported in clinical trials. Our aim was to compare short-term mortality in patients with STEMI who received either intravenous magnesium sulphate or placebo.\n We did a randomised, double-blind trial in 6213 patients with acute STEMI who were assigned a 2 g intravenous bolus of magnesium sulphate administered over 15 min, followed by a 17 g infusion of magnesium sulphate over 24 h (n=3113), or matching placebo (n=3100). Our primary endpoint was 30-day all-cause mortality. At randomisation, patients were stratified by their eligibility for reperfusion therapy. The first stratum included patients who were aged 65 years or older and eligible for reperfusion therapy, and the second stratum included patients of any age who were not eligible for reperfusion therapy. Analysis was by intention-to-treat.\n At 30 days, 475 (15.3%) patients in the magnesium group and 472 (15.2%) in the placebo group had died (odds ratio 1.0, 95% CI 0.9-1.2, p=0.96). No benefit or harm of magnesium was observed in eight prespecified subgroup analyses of patients and in 15 additional exploratory subgroup analyses. After adjustment for factors shown to effect mortality risk in a multivariate regression model, no benefit of magnesium was observed (1.0, 0.8-1.1, p=0.53).\n Early administration of magnesium in high-risk patients with STEMI has no effect on 30-day mortality. In view of the totality of the available evidence, in current coronary care practice there is no indication for the routine administration of intravenous magnesium in patients with STEMI.", "The effects of magnesium on the incidence of arrhythmias and on mortality were evaluated in 103 patients with documented acute myocardial infarction (AMI) in a randomized, double-blind, placebo-controlled study. Fifty patients received a magnesium infusion for 48 hours and 53 received only the vehicle (isotonic glucose) as placebo. The baseline characteristics of the population were similar in the 2 groups. Tachyarrhythmias requiring drug therapy were recorded in 32% of the patients in the magnesium group and in 45% of the placebo group. Conduction disturbances were found in 23% of the placebo group as compared to 14% in the magnesium group. The intrahospital mortality was 2% (1 patient) in the magnesium group, compared to 17% (9 patients) in the placebo group (p less than 0.01). No adverse effects were observed during and after the magnesium infusion. These data support a possible protective role of magnesium in patients with AMI.", "A total of 252 patients with suspected acute myocardial infarction were included in a double blind study and randomised to 50 mmol magnesium sulfate infusion under 20 h or corresponding placebo. Acute myocardial infarction was verified in 117 patients and 59% of these had concomitant treatment with thrombolysis. One-hundred ninety-four patients had Holter registrations during the first day in the coronary care unit. Intention-to-treat analysis showed an increase in long RR-intervals (> 3 s) in the magnesium treated group (P = 0.006) and a tendency toward a reduction in episodes of ventricular premature complexes in triplets (P = 0.09). During hospital stay and a mean of 22 months follow-up, 23 fatal events occurred in the magnesium allocated group and 31 fatal events among the placebo allocated group (P = 0.1). Mortality rate from cardiac disease was reduced by 54% (95% C.I. 30-99%, P < 0.05). Subgroup analysis on acute myocardial infarction patients showed a 48% mortality risk reduction in the magnesium treated acute myocardial infarction group compared to the placebo treated acute myocardial infarction group (95% C.I. 23-104%, P = 0.06). There was no significant interaction between the effects of magnesium and thrombolytic treatment on total mortality or cardiac events. This study supports the results of other small double blind placebo controlled studies regarding effects of magnesium therapy on mortality in acute myocardial infarction, but are in discordance to the conclusion from the ISIS-4 study. The reasons for these discrepancies cannot be elucidated by our data.", "Various methods have been proposed and tried to limit the extent of myocardial damage at the time of infarction. We chose to assess the usefulness of intravenous magnesium in this regard because of its important role in myocardial metabolism and function and the suggestion of its deficiency in ischemic hearts. A double-blind randomized trial was carried out and results analyzed in 76 patients. At the end of the infusion period the mean serum Mg++ level for the treated group was 3.6 versus 1.9 mg/dl for the control group. The estimated size of infarction (as measured by MB-CK release) was not significantly smaller overall in the treated group (37.4 +/- 4.3 vs. 45.6 +/- 4.6 MB-CK g/Eq), but was significantly smaller in the treated subgroup without heart failure (31.6 +/- 5.8 vs. 44.7 +/- 4.8 MB-CK g/Eq). A trend toward less ventricular ectopy was seen in the group treated with magnesium. There was significantly less lidocaine used for the treatment of ventricular dysrhythmias in this group. Magnesium supplementation in patients undergoing acute coronary events is promising and deserves further study.", "Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that magnesium sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of magnesium sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous magnesium sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous magnesium. Group II consisted of 98 patients who received isotonic glucose as a placebo. Magnesium reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received magnesium sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving magnesium sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (> 70 years) (9% vs 23%; p = 0.09). In conclusion, magnesium sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI.", "To examine the effect of doubling serum magnesium concentration on the incidence of arrhythmias in patients with suspected acute myocardial infarction.\n Randomised double blind clinical trial.\n Coronary care unit of a teaching hospital.\n Clinical data were collected on 2316 randomised patients with suspected acute myocardial infarction. Holter monitoring was performed in a subgroup of 70 patients and analysed in 48 patients in whom acute myocardial infarction was confirmed.\n By random allocation, patients received either an intravenous loading dose of 8 mmol magnesium sulphate over five minutes plus 65 mmol over the next 24 hours, or equal volumes of saline.\n (a) Clinically documented arrhythmias; (b) use of antiarrhythmic treatments, cardioversion, and insertion of a pacemaker; (c) incidence of all abnormal rhythms during Holter monitoring.\n In the main trial the incidence of rhythm disturbance while in the coronary care unit (expressed as the odds ratio (OR) for magnesium: placebo and its 95% confidence interval) was not significantly different between treatment groups for ventricular fibrillation (OR 0.74; 0.46 to 1.20), ventricular tachycardia (OR 0.87; 0.63 to 1.20), supraventricular tachycardia (OR 0.69; 0.38 to 1.26), atrial fibrillation (OR 0.92; 0.69 to 1.23), or heart block of any degree (OR 1.17; 0.83 to 1.65). Sinus bradycardia was significantly more common in the magnesium group (OR 1.38; 1.03 to 1.85; p = 0.02). These findings were corroborated by the use of treatments for rhythm disturbance and the data from Holter monitoring.\n The regimen of intravenous magnesium sulphate used here had no significant effect on arrhythmia in acute myocardial infarction. The reduction in mortality that has been shown with this form of treatment is not attributable to suppression of life threatening rhythm disturbances.", "It has been reported that both nicorandil and magnesium have a cardioprotective effect in experimental ischemia - reperfusion models. In the present study, the cardioprotective effects of nicorandil and magnesium as an adjunct to reperfusion therapy in patients with acute myocardial infarction (AMI) were compared.\n Forty consecutive patients with AMI caused by occlusion of anterior descending coronary artery were randomized into 3 groups: (1) Group N: nicorandil was given as 4 mg iv and 4 mg ic before reperfusion, followed by continuous infusion at 4 mg/h for 24 h; (2) Group M: magnesium was administered at 10 mmol iv before reperfusion, followed by continuous infusion at 0.4 mmol/h for 24 h; and (3) Group C: neither nicorandil nor magnesium was given. Left ventriculography was performed immediately after reperfusion and 3 months later. There was no significant change in regional wall motion (RWM) in either Group C or M, whereas that of group N improved significantly. The change in RWM in Group N was significantly greater than in Group C (Group N: 0.92+/-0.92, Group M: 0.44+/-0.80, Group C: -0.01+/-0.65, p<0.05).\n The early administration of nicorandil as an adjunct to reperfusion is useful for cardioprotection in AMI, but magnesium is not." ]

[ "4777936", "8637787", "13010995", "8637789", "5953287", "5695575" ]

[ "Epidemiology and prophylaxis of rheumatic fever in Delhi--a five year follow-up.", "Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever.", "Prophylaxis of recurrences of rheumatic fever with penicillin given orally; final report of a five year study.", "Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG.", "Discontinuation of antistreptococcal prophylaxis. A double-blind study in rheumatic patients free of heart disease.", "Prophylaxis of recurrent rheumatic fever. Therapeutic-continuous oral penicillin vs monthly injections." ]

[ "nan", "To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF).\n We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained.\n Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers.\n True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%.\n This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.", "nan", "This prospective study was aimed at answering two important questions: 1) Is a biweekly schedule of 1.2 million U intramuscular benzathine penicillin G (BPG) superior to a 4-week one in the prevention of upper respiratory Group A beta-hemolytic streptococcal (GABHS) infections and rheumatic fever (RF) recurrences? 2) Is there a difference in the bioavailability of BPG obtained from different manufacturers?\n Three hundred sixty rheumatic patients aged 4 to 20 years were randomly assigned to either a biweekly (190 patients) or 4-week (160 patients) BPG prophylactic schedule and were followed-up monthly for 2 years by clinical examination, throat swab culture for GABHS and measurement of antistreptolysin O titer to detect GABHS infection and/or recurrences of RF (according to revised Jones' Criteria). Thereafter, 34 rheumatic subjects, aged 8 to 16 years were randomly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG brand (22 patients) or an imported one (12 patients). Sera of all patients were tested for penicillin level by plate diffusion method on days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 after the intramuscular injection of BPG.\n The GABHS infection rate was found to be 0.2% and 0.3% for patients on the biweekly and 4-week BPG schedules, respectively, with no significant differences between them. However, the RF recurrence rate/patient/year for the 4-week schedule patients (0.12) was double that for the biweekly schedule ones (0.06). Estimation of the bioavailability of the two different brands of BPG demonstrated a difference in their pharmacokinetics and a decrease in the serum penicillin concentration below the minimum inhibitory concentration 3 weeks after the injection of either brand.\n Although a biweekly schedule may not be superior in preventing upper respiratory GABHS infection, it may play a role in preventing the sequelae of such infections. The short duration of penicillinemia explains the superiority of the 2-week schedule in RF prophylais. The difference in the pharmacokinetics of penicillin brands might contribute to the high recurrence rate of RF reported in Egypt.", "nan", "nan" ]

[ "10591384", "7491044", "15925877", "1579252", "8322373", "19097942", "16574922", "18296121", "8805730", "7493170", "10753980", "7563451", "9788453", "15569863", "18815396", "17702958", "12971850" ]

[ "Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke.", "Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial--Italy (MAST-I) Group.", "Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke.", "Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke.", "Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group.", "Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study.", "Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset.", "Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.", "Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group.", "A pilot study of streptokinase for acute cerebral infarction.", "The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g) : results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators.", "Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS)", "Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators.", "The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase.", "Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.", "Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan.", "[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction]." ]

[ "Recombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.\n To test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset.\n The Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study is a phase 3, placebo-controlled, double-blind randomized study conducted between December 1993 and July 1998, with up to 90 days of follow-up.\n One hundred forty university and community hospitals in North America.\n An intent-to-treat population of 613 acute ischemic stroke patients was enrolled, with 547 of these treated as assigned within 3 to 5 hours of symptom onset. A total of 39 others were treated within 3 hours of symptom onset, 24 were treated more than 5 hours after symptom onset, and 3 never received any study drug.\n Administration of 0.9 mg/kg of rt-PA (n = 272) or placebo (n = 275) intravenously over 1 hour.\n Primary efficacy was an excellent neurologic recovery at day 90 (National Institutes of Health Stroke Scale [NIHSS] score of < or =1); secondary end points included excellent recovery on functional outcome measures (Barthel index, modified Rankin scale, and Glasgow Outcome Scale) at days 30 and 90. Serious adverse events were also assessed.\n In the target population, 32% of the placebo and 34% of rt-PA patients had an excellent recovery at 90 days (P = .65). There were no differences on any of the secondary functional outcome measures. In the first 10 days treatment with rt-PA significantly increased the rate of symptomatic intracerebral hemorrhage (ICH) (1.1% vs 7.0% [P<.001]), a symptomatic ICH (4.7% vs 11.4% [P = .004]), and fatal ICH (0.3% vs 3.0% [P<.001]). Mortality at 90 days was 6.9% with placebo and 11.0% with rt-PA (P = .09). Results in the intent-to-treat population were similar.\n This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.", "In ischaemic stroke, thrombolytic drugs speed the recanalisation of intracerebral arteries. The effects of aspirin are not known. A trial was conducted to determine whether, separately or together, streptokinase and aspirin have clinical benefits in acute ischaemic stroke similar to those in acute myocardial infarction. 622 patients with acute ischaemic stroke within 6 hours of symptom onset were randomised with a 2 x 2 factorial design to (i) a 1-hour intravenous infusion of 1.5 MU streptokinase, (ii) 300 mg/day buffered aspirin for 10 days, (iii) both active treatments, or (iv) neither. Early results raised a question whether the trial should be continued. Streptokinase (alone or with aspirin) was associated with an excess of 10-day case fatality (odds ratio 2.7; 95% confidence interval 1.7-4.3; 2p < 0.00001). Of the four groups randomised, only patients allocated to streptokinase plus aspirin had a significantly higher risk of early death than those given neither streptokinase nor aspirin (odds ratio 3.5; 95% CI 1.9-6.5; 2p < 0.00001). Streptokinase (alone or with aspirin) and aspirin (alone or with streptokinase) reduced, albeit not significantly, the incidence of combined six-month case fatality and severe disability: odds ratio for streptokinase 0.9 (95% CI 0.7-1.3) and odds ratio for aspirin 0.9 (95% CI 0.6-1.3). The risk of early death with thrombolytic treatments should be weighed against the potential benefit of a marginal reduction of severe disability after the first six months.", "Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy.\n Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion.\n Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group.\n These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.\n Copyright 2005 S. Karger AG, Basel.", "To determine the effect of intravenous recombinant tissue plasminogen activator (rt-PA) on vascular and neurologic outcomes, we enrolled 31 patients with acute carotid artery-territory ischemic stroke within 6 hours from symptom onset in a randomized, double-blind, placebo-controlled study. We gave either rt-PA (duteplase at the dose of 20 or 30 mega-international units [MIU]) or placebo intravenously for 60 minutes in patients randomly assigned to the three groups. A comparison between the baseline and postinfusion angiograms showed that complete or partial reperfusion occurred in 50% (5/10) of patients treated with 30 MIU rt-PA, 44% (4/9) of those treated with 20 MIU rt-PA, and 17% (2/12) in the control group. In patients with middle cerebral artery occlusions, reperfusion occurred in 71% (5/7) of the 30-MIU group, in 67% (4/6) of the 20-MIU group, and in 13% (1/8) of the control group. Patients treated with 30 MIU rt-PA showed a significantly early and better clinical improvement, as measured by the neurologic scale, than did those treated with placebo. Parenchymal hemorrhage occurred in one patient in each group, and frequency of clinically insignificant hemorrhagic infarction was comparable among the treatment groups. No major systemic complications occurred in any group. These results support the efficacy of intravenous infusion of rt-PA soon after the onset of stroke in producing rapid thrombolysis and neurologic recovery; it may be of particular value in patients with thromboembolic occlusion in the middle cerebral artery.", "Early thrombolytic therapy with recombinant tissue-type plasminogen activator is a theoretically attractive approach to the treatment of acute focal cerebral ischemia. In preparation for a larger multicenter trial, three centers piloted a protocol for a randomized, double-blind, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator begun within 3 hours of the onset of symptoms of acute stroke to test its feasibility and to explore trends.\n Eligible patients had pretreatment computed tomographic scanning, gave informed consent, and began treatment with either 0.85 mg/kg recombinant tissue-type plasminogen activator or placebo as soon as possible, but no later than 180 minutes after stroke onset. Patients were stratified by whether treatment was begun within 90 minutes or 91 to 180 minutes from onset. The primary end point was the proportion of patients in each group who improved by 4 or more points on the National Institutes of Health Stroke Scale at 24 hours, as determined by a separate blinded evaluator.\n Twenty-seven patients were randomized: 20 (10 recombinant tissue-type plasminogen activator, 10 placebo) within 90 minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo) from 91 to 180 minutes. Median baseline Stroke Scale scores were 16 (minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen activator-treated group and 11 (minimum = 3, maximum = 21) for the control subjects in the group treated within 90 minutes. Six patients treated with recombinant tissue-type plasminogen activator within 90 minutes improved by 4 or more points at 24 hours compared with 1 patient in the placebo group (P < .05, Fisher's Exact Test). Two patients in each group in the 91- to 180-minute arm improved. One fatal intracerebral hemorrhage occurred in the placebo group.\n A randomized, double-blind, placebo-controlled trial of recombinant tissue-type plasminogen activator very early in acute stroke is feasible. Preliminary observations suggest that recombinant tissue-type plasminogen activator treatment within 90 minutes may be associated with early neurological improvement. Larger studies are needed so that the potentially serious short-term risks of this treatment can be assessed in relation to meaningful long-term benefit.", "Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI).\n In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 microg/kg desmoteplase, 125 microg/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT00111852.\n Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 microg/kg desmoteplase; 66 received 125 microg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6-14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 microg/kg desmoteplase, 36% (24 of 66) for 125 microg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 microg/kg desmoteplase 14.0% (0.5 cm(3)); 125 microg/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9 cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for 90 microg/kg desmoteplase, 4.5% (3 of 66) for 125 microg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 microg/kg desmoteplase; 21% [14 of 66] for 125 microg/kg desmoteplase; and 6% [4 of 63] for placebo).\n The DIAS-2 study did not show a benefit of desmoteplase given 3-9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase.\n PAION Deutschland GmbH; Forest Laboratories.", "Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.\n DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.\n Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022).\n Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).", "Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI).\n We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537.\n We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion.\n Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.", "To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours.\n Randomized, double-blind, placebo-controlled trial with 3-month follow-up.\n A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994.\n Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour.\n Combined death and disability score (Barthel index <60) 3 months after the stroke.\n Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2%[12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (P=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21).\n The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.", "We evaluated intravenous streptokinase in the treatment of cerebral infarction. Following neurological assessment and cerebral computed tomography (CT), patients aged 40-80 years with symptoms of anterior circulation acute ischaemic stroke were given 1.5 M units streptokinase or saline placebo in a double-blind randomized study. Twenty patients (10 streptokinase, 10 placebo), 11 males, 9 females, aged 57-79 years, were treated out of 512 consecutive admissions to the acute stroke unit over a 2-year period. Initial CT was normal in 11 (6 placebo, 5 streptokinase) and showed early signs of cerebral infarction in nine (4 placebo, 5 streptokinase). Median times from symptom onset to treatment were 5.2 h (placebo) and 5.8 h (streptokinase). Streptokinase treatment was associated with symptomatic hypotension in one patient. Repeat CT at 72 h demonstrated intracerebral haematoma in two patients and haemorrhagic infarction in one patient in the streptokinase group; the two cases of haematoma formation were associated with neurological deterioration and death. One patient in the placebo group had evidence of haemorrhagic infarction at 72 h. There were three deaths in each treatment group, all within the first 14 days. Patients with acute stroke can be evaluated with CT and treated with streptokinase within 6 h, but the opportunity for treatment is currently limited to few patients. Streptokinase treatment is not without risk, but potential clinical benefit justifies ongoing multicentre randomized trials.", "The Thrombolytic Therapy in Acute Ischemic Stroke Study, which started in August of 1991, was designed to assess the efficacy and safety of intravenous rtPA (alteplase) in patients with acute (0 to 6 hours) ischemic stroke. In October 1993 enrollment was halted because of Safety Committee (DMSB) concerns. In December 1993 the time window was changed to 0 to 5 hours, and it was decided to restart enrollment as a separate study (part B). We report here the results of the original study (part A), focusing on evaluating the safety and efficacy of rtPA given between 0 and 6 hours after stroke onset.\n This investigation was a phase II, placebo-controlled, double-blind, randomized study utilizing 0.9 mg/kg IV rtPA or placebo over 1 hour, which was conducted at university and community sites in North America. Except for time to treatment, enrollment criteria were very similar to those of the NINDS rtPA stroke study. Primary efficacy end points were the number of patients with a decrease of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 24 hours and day 30, along with infarct volume at day 30. Secondary end points included mortality and functional recoveries on the Barthel Index and Modified Rankin scale at days 30 and 90.\n A total of 142 patients were enrolled at 42 sites in North America, including 22 <3 hours (15%) and 46 between 5 and 6 hours (32%). The groups were well matched on baseline characteristics, including NIHSS (mean of 13 for both). For the primary end points, a higher percentage of rtPA patients had a 4-point improvement at 24 hours (placebo 21%, rtPA 40%; P=0.02); however, this early effect was reversed by 30 days, with more placebo patients having a 4-point improvement (75%) than patients treated with rtPA (60%, P=0.05). Treatment with rtPA significantly increased the rate of symptomatic intracerebral hemorrhage within 10 days (11% versus 0%, P<0.01) and mortality at 90 days (23% versus 7%, P<0.01).\n This study found no significant rtPA benefit on any of the planned efficacy end points at 30 and 90 days in patients treated between 0 and 6 hours after stroke onset. These negative results apply to patients treated after 3 hours, because only 15% of the patients were enrolled before 3 hours. The risk of symptomatic intracerebral hemorrhage was increased with rtPA treatment, particularly in patients treated between 5 and 6 hours after onset. These results do not support the use of intravenous rtPA for stroke treatment >3 hours after onset.", "To evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke.\n Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial.\n A total of 75 hospitals in 14 European countries.\n A total of 620 patients with acute ischemic hemispheric stroke and moderate to severe neurologic deficit and without major early infarct signs on initial computed tomography (CT).\n Patients were randomized to treatment with 1.1 mg per kilogram of body weight of rt-PA (alteplase) or placebo within 6 hours from the onset of symptoms.\n Primary end points included Barthel Index (BI) and modified Rankin Scale (RS) at 90 days. Secondary end points included combined BI and RS, Scandinavian Stroke Scale (SSS) at 90 days, and 30-day mortality. Tertiary end points included early neurologic recovery (SSS) and duration of in-hospital stay. Safety parameters included mortality and incidence of intracranial or extracranial hemorrhage.\n The distribution of demographic variables was similar among patients in the rt-PA and placebo treatment arms in both the intention-to-treat (ITT) analysis and the explanatory analysis for the target population (TP). A total of 109 patients (17.4%) were included in the trial despite major protocol violations but excluded from the TP. There was no difference in the primary end points in the ITT analysis, while the TP analysis revealed a significant difference in the RS in favor of rt-PA-treated patients (P = .035). Of the secondary end points, the combined BI and RS showed a difference in favor of rt-PA-treated patients in both analyses (P < .001). Neurologic recovery at 90 days was significantly better for rt-PA-treated patients in the TP (P = .03). The speed of neurologic recovery assessed by the SSS was significantly better up to 7 days in the ITT analysis and up to 30 days for the TP in the rt-PA treatment arm. In-hospital stay was significantly shorter in the rt-PA treatment arm in both analyses. There were no statistically significant differences in the mortality rate at 30 days or in the overall incidence of intracerebral hemorrhages among the rt-PA and placebo treatment arms in either analysis. However, the occurrence of large parenchymal hemorrhages was significantly more frequent in the rt-PA-treated patients.\n Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of hemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients.", "Thrombolysis for acute ischaemic stroke has been investigated in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0.9 mg/kg bodyweight) within 6 h of stroke onset.\n This non-angiographic, randomised, double-blind, trial enrolled 800 patients in Europe, Australia, and New Zealand. Computed tomography was used to exclude patients with signs of major infarction. Alteplase (n=409) and placebo (n=391) were randomly assigned with stratification for time since symptom onset (0-3 h or 3-6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0-1) and unfavourable (score 2-6) outcome. Analyses were by intention to treat.\n 165 (40.3%) alteplase-group patients and 143 (36.6%) placebo-group patients had favourable mRS outcomes (absolute difference 3.7%, p=0.277). In a posthoc analysis of mRS scores dichotomised for death or dependency, 222 (54.3%) alteplase-group and 180 (46.0%) placebo-group patients had favourable outcomes (score 0-2; absolute difference 8.3%, p=0.024). Treatment differences were similar whether patients were treated within 3 h or 3-6 h. 85 (10.6%) patients died, with no difference between treatment groups at day 90+/-14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8.8%) alteplase-group patients and 13 (3.4%) placebo-group patients.\n The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0.9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.", "Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI.\n DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 microg/kg, 90 microg/kg, and 125 microg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days.\n Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 microg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 microg/kg; P=0.757) and 60.0% (125 microg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion.\n Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 microg/kg.", "Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke.\n After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events.\n We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events.\n As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)\n 2008 Massachusetts Medical Society", "The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset.\n Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index.\n The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat more frequent in the UK group than in the control group (49.1% and 38.6%, OR: 1.54, 95% CI: 0.73 to 3.23) but did not reach a significant level (P=0.345). However, excellent functional outcome (modified Rankin Scale 0 to 1) at 90 days, a preplanned secondary end point, was more frequent in the UK group than in the control group (42.1% and 22.8%, P=0.045, OR: 2.46, 95% CI: 1.09 to 5.54). There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group (P=0.017). The 90-day cumulative mortality was 5.3% in the UK group and 3.5% in the control group (P=1.000), and intracerebral hemorrhage within 24 hours of treatment occurred in 9% and 2%, respectively (P=0.206).\n The trial was aborted prematurely and the primary end point did not reach statistical significance. Nevertheless, the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome.", "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." ]

[ "1372508", "9307346", "2704497", "1550145", "16602839", "8238159", "2206065", "8238160", "3421250", "1892190", "8885772", "8116706", "14526317", "1407911", "12824971", "11293640" ]

[ "Premature rupture of the membranes: effect of penicillin prophylaxis and long-term outcome of the children.", "Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.", "Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study.", "Erythromycin therapy in preterm premature rupture of the membranes: a prospective, randomized trial of 220 patients.", "Antibiotic therapy for preterm premature rupture of membranes - results of a multicenter study.", "Double-blind; placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture.", "Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial.", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.", "Ampicillin prophylaxis in preterm premature rupture of the membranes: a prospective randomized study.", "Antimicrobial therapy in preterm premature rupture of membranes: results of a prospective, double-blind, placebo-controlled trial of erythromycin.", "Group B Streptococcus and preterm premature rupture of membranes: a randomized, double-blind clinical trial of antepartum ampicillin.", "A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes.", "Duration of antibiotic therapy after preterm premature rupture of fetal membranes.", "Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.", "Antibiotic therapy in preterm premature rupture of membranes: Are seven days necessary? A preliminary, randomized clinical trial.", "Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group." ]

[ "To assess the value of prophylaxis with penicillin in women with premature rupture of membranes (PROM) and the long-term outcome of children born after prolonged PROM, we studied 221 women with this condition. Penicillin (5 mu twice, 6 hours apart) was given intravenously to 50 women and placebo to 51 women, whereas 76 comparable patients were treated without penicillin or placebo. The time interval between PROM and delivery ranged from 14 hours to 56 days. Chorioamnionitis occurred more frequently (p less than 0.05) among patients with placebo (14%) than among those treated with penicillin (2%). One puerperal endometritis appeared in the placebo group compared with none in the penicillin group. One newborn (1.7%) born to a mother with placebo prophylaxis developed septicemia, compared with none in the penicillin group. The outcomes of pregnancies complicated with PROM treated without penicillin or placebo were comparable with those in the placebo group. In addition, we compared somatic and psychomotor development of 159 children born to mothers with prolonged PROM (more than 12 hours; mean, 5.6 days; range, 14 to 1344 hours) with those of 43 children born at similar gestational age within 5 hours after PROM. No pulmonary sequelae could be linked to the long time period between PROM and delivery, but infants born soon after PROM more often (p less than 0.05) had cerebral palsy (8 of 43, 18.6%) than did infants born after prolonged PROM (7 of 159; 4.4%). We conclude that, in cases with PROM, penicillin prophylaxis decreases maternal and neonatal infectious morbidity and that the long interval between PROM and delivery does not impair the long-term outcome for these children.", "Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.\n To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.\n Randomized, double-blind, placebo-controlled trial.\n University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.\n A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.\n Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.\n The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.\n In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).\n We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.", "A randomized study was conducted to investigate the effects of antenatal corticosteroids and ampicillin in the management of preterm pregnancies under 34 weeks complicated by premature rupture of membranes. Patients with documented lecithin/sphingomyelin (L/S) ratios of less than 2.0 and a singleton gestation were eligible to participate in the study. One hundred sixty-five patients qualified and were randomized, using sealed envelopes, to four study groups. All patients were followed expectantly. Group I (41 patients) received neither ampicillin nor corticosteroids. Group II (43 patients) received 24 mg of antenatal betamethasone. Group III (37 patients) received 2 g of intravenous ampicillin every 6 hours, with discontinuation of antibiotic therapy if cultures were negative for pathogenic bacteria. Group IV (44 patients) received both corticosteroids and ampicillin as described for groups II and III, respectively. Compared with patients not receiving corticosteroids, those administered antenatal corticosteroids experienced a reduction in the incidences of respiratory distress syndrome (53 versus 26%), bronchopulmonary dysplasia (23 versus 9%), severe grades of intracranial hemorrhage (15 versus 3%), and patent ductus arteriosus (18 versus 6%), with no difference in the incidence of maternal or neonatal infection. Compared with patients not receiving antenatal antibiotics, the group of patients treated with ampicillin on admission had a lower incidence of clinical chorioamnionitis (4 versus 26%) and neonatal sepsis (5 versus 10%). This reduction in infectious morbidity by antenatal ampicillin was restricted to those patients (28.4% of the study population) colonized with group B streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)", "The use of prophylactic antibiotics in the management of preterm premature rupture of the membranes has not been adequately studied. The purpose of this study was to evaluate the efficacy of oral erythromycin therapy in the prolongation of latency and reduction of infectious morbidity after preterm premature rupture of membranes.\n In this randomized, prospective, double-blind, placebo-controlled study, 220 women at 20 to 35 weeks' gestation were evaluated. Subjects received oral erythromycin 333 mg (n = 106) or indistinguishable placebo (n = 114) every 8 hours from randomization to delivery.\n Prolongation of latency was identified with erythromycin therapy (p = 0.02), particularly for those destined to have chorioamnionitis (p = 0.003) and those with oligohydramnios (p = 0.01). No decrease in the incidence of maternal or neonatal infectious morbidity was seen.\n Oral erythromycin delays, but does not prevent, the onset of clinical infection when administered to women with preterm premature rupture of membranes. This regimen does not decrease neonatal morbidity and mortality.", "To evaluate whether primary application of mezlozillin in preterm premature rupture of membranes (pPROM) prolongs pregnancy and lowers neonatal morbidity.\n In this prospective, randomized, double blind, placebo-controlled multicenter study a total of 105 pregnant women with pPROM between 24 + 0 and 32 + 6 weeks of gestation were examined receiving i.v. injections of corticoids and tocolytics as well as mezlocillin (3 x 2 g/d) or placebo. Assessed factors were prolongation of pregnancy and neonatal morbidity such as neonatal infection, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC).\n Prolongation of pregnancy by more than 7 days was achieved in 63.8% of the mezlocillin group versus 44.8% of the placebo group (P < 0.05). The babies of mothers treated with anibiotics had fewer neonatal infections, RDS, IVH and NEC. Total morbidity was significantly lowered in the verum group (P = 0.02).\n Antibiotic administration following preterm premature rupture of membranes is associated with a prolongation of pregnancy and a reduction of neonatal infectious morbidity.", "We attempted to test whether antibiotic therapy prolongs pregnancy in preterm premature rupture of membranes, because preterm premature rupture of membranes is frequently associated with chorionic-decidual infection.\n Women with preterm premature rupture of membranes and a singleton gestation at 24 to 34 completed weeks were randomized to receive either piperacillin 3 gm or placebo intravenously every 6 hours for 72 hours and were managed conservatively until spontaneous delivery, chorioamnionitis, or fetal distress.\n Between January 1987 and January 1992, a total of 75 patients were randomized to receive piperacillin (n = 38) or placebo (n = 37). There were no differences between the piperacillin group and the placebo group in mean gestational age at randomization (30.2 +/- 3 vs 30.3 +/- 2.9 weeks). However, a greater number of patients had pregnancy prolonged beyond 7 days (42.1% vs 10.8% p = 0.005) and the mean latency period was significantly prolonged (11.4 +/- 18.8 vs 6.1 +/- 13.6 days, p = 0.001) in the piperacillin group compared with the control groups.\n Use of intravenous piperacillin for 72 hours in preterm premature rupture of membranes significantly prolongs the latency period between membrane rupture and delivery.", "The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.", "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.", "It is hypothesized that ampicillin may treat subclinical deciduitis and prolong the \"effective\" latent period in patients with preterm premature rupture of the membranes. We studied 82 patients with preterm rupture of membranes who were managed expectantly and were randomly assigned either to receive ampicillin prophylaxis (n = 43) or not to receive ampicillin prophylaxis (n = 39). Patients were excluded from study entry on admission if they had suspected or frank chorioamnionitis, active preterm labor, a history of penicillin allergy, multiple gestation, or cervical cerclage. There were no significant differences between the groups in duration of membrane rupture prior to admission, gestational age at membrane rupture, use of steroids and tocolysis, and demographic factors. Life-table analysis showed that the risk of delivery was significantly lower for the group of patients receiving prophylactic ampicillin. The incidence of neonatal infection was significantly lower in the ampicillin group, 1 (2%) versus 6 (17%), p less than 0.04.", "This study was conducted to evaluate the effectiveness of oral erythromycin treatment in safely prolonging pregnancy among women experiencing preterm premature rupture of membranes. Sixty-five women were randomly assigned to receive double-blind treatment with either erythromycin base or an identical-appearing placebo three times daily for 7 days. Only women between 23 and 34 completed weeks' gestation who did not have an indication for delivery were enrolled in the study. Pretreatment microbiologic tests were obtained and women were followed expectantly. Fifty-five women and their newborns completed the protocol and were fully evaluated. Overall, time from rupture of membranes to onset of labor and to delivery was longer, although not significantly, for erythromycin-treated women. Similarly, there was a trend for reduced neonatal intensive care (level II, p = 0.07). When gestational age at enrollment was controlled, erythromycin treatment of women between 28 to 32 weeks' gestation was associated with a prolonged interval from enrollment to delivery [erythromycin: 292 hours (5 to 679); placebo: 54 (12 to 323); p less than 0.044]. Fifty percent of erythromycin-treated women between 28 to 32 weeks' gestation continued their pregnancies at least 13 days after premature rupture of membranes, whereas 50% of placebo-treated women were delivered of infants within 4 days (p = 0.02). Erythromycin treatment among women less than 28 and between 33 to 34 weeks' gestation was not associated with prolonged latency or other changes. There were no differences between erythromycin- and placebo-treated women in the occurrence of clinically recognized chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. In this double-blind, placebo-controlled trial, erythromycin treatment was well tolerated, safe, and associated with prolongation of pregnancy and reduced intensive neonatal care requirements for selected mother-newborn pairs with preterm premature rupture of membranes.", "Our purpose was to determine whether ampicillin prolongs the latency period after preterm premature rupture of membranes in patients colonized with group B Streptococcus.\n Sixty patients presenting at < or = 35 weeks' gestation with preterm premature rupture of membranes were included in the study. Cervical, vaginal, and perianal cultures for group B premature rupture were obtained. The participants then were randomized to receive either ampicillin or placebo intravenously for 24 hours and then orally until hospital discharge or delivery. All patients were treated without the use of tocolytic drugs. The chi(2) test, Fisher exact test, Student t test, and Wilcoxon signed-rank test were used for statistical analysis when appropriate.\n Fifteen patients had cultures positive for group B Streptococcus. Patients with cultures positive for group B Streptococcus who received ampicillin (n = 8) were more likely not to have been delivered of their infants 48 hours after preterm premature rupture of membranes than patients who received placebo (n = 7), a statistically significant difference (100% vs 43%; p = 0.01; relative risk 2.3; 95% confidence interval 1.2 to 4.5). Seven days after preterm premature rupture of membranes, however, there was no significant difference in percentage of patients with cultures positive for group B Streptococcus who remained undelivered (63% vs 29%; p = 0.19; relative risk, 2.2; 95% confidence interval 0.7 to 7.1). Among patients with cultures negative for group B Streptococcus, there was a trend for patients who received ampicillin to remain undelivered 48 hours after preterm premature rupture of membranes compared with those who received placebo, but the difference was not statistically significant (87% vs 64%; p = 0.07; relative risk, 1.4; 95% confidence interval 1.0 to 1.9). There also was no difference in percentage of patients with cultures negative for group B Streptococcus who remained undelivered 7 days after preterm premature rupture of membranes 39% vs 27%; p = 0.40; relative risk, 1.4; 95% confidence interval 0.61 to 3.3). There were no differences between the treatment and placebo arms of the group B Streptococcus positive and negative cohorts in incidence of cesarean section, chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity.\n Use of antibiotics increases the percentage of patients with cultures positive for group B Streptococcus who remain undelivered 48 hours after preterm premature rupture of membranes. Antibiotic therapy may provide a window of opportunity for maternal treatment with corticosteroids to decrease the risk for neonatal morbidity among these preterm gestations.", "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.", "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.", "The purpose of this study was to determine whether 3 days of broad-spectrum antibiotic therapy, which is intended to prolong latency in patients with preterm premature rupture of membranes, is comparable to 7 days of therapy.\n Patients with preterm premature rupture of membranes at three separate study sites were asked to participate in this intent-to-treat, prospective, randomized trial. They were assigned randomly to either 3 or 7 days of ampicillin-sulbactam (3 g intravenously every 6 hours). The primary outcome of interest was the latency period from membrane rupture to delivery.\n Forty-two individuals were enrolled in each group. No difference was noted in the latency interval between the two groups (3 days, 214 +/- 225 hours, vs 7 days, 229 +/- 218 hours). A significantly higher number of patients in the 3-day group completed therapy (80.1% vs 47.6%, P =.003). No other parameters were significantly different between the two groups. No adverse events or trends were noted in either group.\n There appears to be no difference in the latency period between 3 and 7 days of ampicillin-sulbactam antibiotic therapy. More patients are needed to exclude a type II error.", "Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue.\n 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.\n Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis.\n Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability. However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis. A follow-up study of childhood development and disability after pPROM is planned." ]

[ "15006018", "18455221", "16675212", "17362472" ]

[ "Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.", "Comparison of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol dry powder inhaler in asthma patients.", "EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma.", "Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations." ]

[ "Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms.\n This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens.\n Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW).\n The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011).\n Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.", "The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI.\n We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI.\n This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2).\n There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated.\n Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.", "This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids.\n The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group.\n The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated.\n Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.", "This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 microg/day) received budesonide/formoterol 160/4.5 microg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 microg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 microg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p=0.0034 and p=0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49-0.76, p<0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57-0.90, p=0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol." ]

[ "12882865", "21310502", "8134442", "8941460", "12787692", "1303408", "20427683", "19239860" ]

[ "Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study.", "Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy.", "Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double-blind study.", "Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study.", "The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial.", "Hyperbaric oxygen therapy in diabetic foot.", "Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes.", "Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers." ]

[ "To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers.\n From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline.\n HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group.\n In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.", "This study compared the effectiveness of extracorporeal shockwave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) in chronic diabetic foot ulcers.\n The ESWT group (39 patients/44 feet) received shockwave therapy twice per week for total six treatments. The HBOT group (38 patients/40 feet) received hyperbaric oxygen therapy daily for total 20 treatments. Evaluations included clinical assessment, blood flow perfusion scan and histopathological examination.\n The overall clinical results showed completely healed ulcers in 57% and 25% (P = 0.003); ≥ 50% improved ulcers in 32% and 15% (P = 0.071); unchanged ulcers in 11% and 60% (P < 0.001) and none worsened for the ESWT and the HBOT group respectively. The blood flow perfusion rates were comparable between the two groups before treatment (P = 0.245), however, significant differences were noted after treatment favoring the ESWT group (P = 0.002). Histopathological examination revealed considerable increases in cell proliferation and decreases in cell apoptosis in the ESWT group as compared to the HBOT group.\n ESWT is more effective than HBOT in chronic diabetic foot ulcers. ESWT-treated ulcers showed significant improvement in blood flow perfusion rate and cell activity leading to better healing of the ulcers relative to HBOT in chronic diabetic foot ulcers.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.", "To evaluate the effect of hyperbaric oxygen therapy on chronic wound healing, 16 otherwise healthy patients who had nondiabetic, chronic leg ulcers with no large vessel disease were included in a double-blind study. Patients were grouped according to age and then randomly assigned to two groups breathing either air or oxygen at 2.5 atmospheres of absolute pressure for 90 minutes 5 days per week for a total of 30 treatments. The wound area was copied onto transparent film covering the wound and then measured using only one matching wound from each patient. The mean decrease of the wound areas at weeks 2, 4, and 6 in the oxygen group were 6 percent (SD +/- 14), 22 percent (SD +/- 13), and 35.7 percent (SD +/- 17), respectively, and in the air group, 2.8 percent (SD +/- 11), 3.7 percent (SD +/- 11), and 2.7 percent (SD +/- 11), respectively, giving a p value less than 0.05 at week 4, and a p value less than 0.001 at week 6 between the groups using the Mann-Whitney U test. These data indicate that hyperbaric oxygen therapy may be used as a valuable adjunct to conventional therapies when nondiabetic wounds do not heal.", "To evaluate the effectiveness of systemic hyperbaric oxygen therapy (s HBOT) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer.\n From August 1993 to August 1995, 70 diabetic subjects were consecutively admitted into our diabetologic unit for foot ulcers. All the subjects underwent our diagnostic-therapeutic protocol and were randomized to undergo s-HBOT. Two subjects, one in the arm of the treated group and one in the arm of nontreated group, did not complete the protocol and were therefore excluded from the analysis of the results. Finally, 35 subjects received s-HBOT and another 33 did not.\n Of the treated group (mean session = 38.8 +/- 8), three subjects (8.6%) underwent major amputation: two below the knee and one above the knee. In the nontreated group, 11 subjects (33.3%) underwent major amputation: 7 below the knee and 4 above the knee. The difference is statistically significant (P = 0.016). The relative risk for the treated group was 0.26 (95% CI 0.08-0.84). The transcutaneous oxygen tension measured on the dorsum of the foot significantly increased in subjects treated with hyperbaric oxygen therapy: 14.0 +/- 11.8 mmHg in treated group, 5.0 +/- 5.4 mmHg in nontreated group (P = 0.0002). Multivariate analysis of major amputation on all the considered variables confirmed the protective role of s-HBOT (odds ratio 0.084, P = 0.033, 95% CI 0.008-0.821) and indicated as negative prognostic determinants low ankle-brachial index values (odds ratio 1.715, P = 0.013, 95% CI 1.121-2.626) and high Wagner grade (odds ratio 11.199, P = 0.022, 95% CI 1.406-89.146).\n s-HBOT, in conjunction with an aggressive multidisciplinary therapeutic protocol, is effective in decreasing major amputations in diabetic patients with severe prevalently ischemic foot ulcers.", "ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications. The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers.\n eighteen diabetic patients with ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind study. Patients were randomly assigned either to receive 100% oxygen (treatment group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min daily (total of 30 treatments).\n healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group. The median decrease of the wound areas in the treatment group was 100% and in the control group was 52% (p=0.027). Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen, there was a potential saving in the total cost of treatment for each patient during the study.\n hyperbaric oxygen enhanced the healing of ischaemic, non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible.", "To study the effect of hyperbaric oxygen therapy in chronic diabetic foot lesions, a prospective controlled study was undertaken. Thirty diabetics with chronic foot lesions were randomised to study group (conventional management and 4 sessions of hyperbaric oxygen therapy) and control group (conventional management). The patients were assessed for average hospital stay, control of infection and wound healing. The control of infection spread was quicker. Positive cultures decreased from initial 19 to 3 in study group as against from 16 to 12 in the control group. (p < 0.05). This difference was most pronounced for Escherichia coli. Also, the need for major amputation was significantly less in the study group (n = 2) as against the control group (n = 7) (p < 0.05). The average hospital stay was not affected. We conclude that hyperbaric oxygen therapy can be safely used and is beneficial as an adjuvant therapy in chronic diabetic foot lesions.", "Chronic diabetic foot ulcers are a source of major concern for both patients and health care systems. The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) in the management of chronic diabetic foot ulcers.\n The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers (HODFU) study was a randomized, single-center, double-blinded, placebo-controlled clinical trial. The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air. Treatments were given in a multi-place hyperbaric chamber for 85-min daily (session duration 95 min), five days a week for eight weeks (40 treatment sessions). The study was performed in an ambulatory setting.\n Ninety-four patients with Wagner grade 2, 3, or 4 ulcers, which had been present for >3 months, were studied. In the intention-to-treat analysis, complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up: 25/48 (52%) in the HBOT group and 12/42 (29%) in the placebo group (P = 0.03). In a sub-analysis of those patients completing >35 HBOT sessions, healing of the index ulcer occurred in 23/38 (61%) in the HBOT group and 10/37 (27%) in the placebo group (P = 0.009). The frequency of adverse events was low.\n The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes.", "Hyperbaric oxygen therapy can be used as an adjunct to standard wound care in the treatment of diabetic patients with foot ulcers. We undertook a prospective, randomized investigation of the use of hyperbaric oxygen therapy versus standard therapy for the treatment of foot ulcers in diabetic patients. A number of demographic variables were analyzed in regard to wound healing. We noted that foot ulcers in patients in the hyperbaric oxygen therapy group were more likely to heal, and were more likely to undergo amputation distal to the metatarsophalangeal joint compared with those patients receiving standard therapy without hyperbaric oxygen. We feel that hyperbaric oxygen therapy should be considered a useful adjunct in the management of foot ulcers in diabetic patients." ]

[ "3524742", "9462389", "3566123", "12027979", "11260099" ]

[ "De-functioning stomas: a prospective controlled trial comparing loop ileostomy with loop transverse colostomy.", "Temporary decompression after colorectal surgery: randomized comparison of loop ileostomy and loop colostomy.", "Colostomy or ileostomy after colorectal anastomosis?: a randomised trial.", "Randomized clinical trial comparing loop ileostomy and loop transverse colostomy for faecal diversion following total mesorectal excision.", "Stoma-related complications are more frequent after transverse colostomy than loop ileostomy: a prospective randomized clinical trial." ]

[ "Patients undergoing colorectal surgery who required a defunctioning stoma were randomly allocated to receive either a loop ileostomy (n = 23) or transverse loop colostomy (n = 24). Assessment was made during construction, immediately postoperatively, during the period of outpatient supervision and before and after stoma closure. The ileostomy was associated with significantly less odour than the colostomy (P less than 0.01) and required significantly less appliance changes (P less than 0.05). Furthermore eleven patients (58 per cent) with a colostomy experienced three or more problems with stoma management compared with only three patients (18 per cent) with an ileostomy (P less than 0.05). Wound infection was also significantly more common after closure of the colostomy compared with the ileostomy. Both types of stoma were demonstrated objectively to defunction the distal bowel almost completely. These results indicate that a loop ileostomy is the procedure of first choice when a stoma is needed to defunction the distal colorectum.", "Loop ileostomy or loop transverse colostomy for temporary decompression of a left colonic anastomosis represents an important issue in abdominal surgery.\n A randomized study, comparing loop ileostomy (n = 37; group 1) or loop transverse colostomy (n = 39; group 2), was conducted. Patients were followed from construction to closure of the stoma.\n Age, weight, sex and indication for surgery were similar in both groups. After stoma construction complications were reported in nine of 37 patients in group 1 and in one of 39 in group 2 (P < 0.01), leading to postoperative death in five of 37 in group 1 and one of 39 in group 2. In the period between stoma construction and closure significant differences were observed only in prolapse rate (one of 32 group 1, 16 of 38 group 2; P < 0.01), need for temporary adaptation of clothing (eight of 32 group 1, 22 of 38 group 2; P < 0.01) and dietary guidelines (23 of 32 group 1, four of 38 group 2; P < 0.01). One patient died in group 1 and four in group 2; the deaths were not stoma related. After stoma closure eight of 29 patients in group 1 had complications and there were two deaths compared with three of 32 and no deaths in group 2.\n Both types of stoma carry a high complication rate with a considerable associated mortality rate. The interval between stoma construction and closure has substantial impact on social and economic status. Based on all three phases studied, routine use of transverse colostomy is advised if decompression of the left colon is indicated.", "Sixty one patients were entered in a randomised trial to compare transverse loop colostomy with loop ileostomy after a colorectal anastomosis thought to be at risk of dehiscence. Radiologically proven breakdown of the colorectal anastomosis occurred in 13% of these selected patients and most frequently in the colostomy group. Ileostomies functioned earlier than colostomies (P less than 0.001) but there was no other significant difference in outcome between the groups. In 52 patients intestinal continuity was restored by excision of the stoma within a month of construction with no difference in morbidity between the two groups. A loop ileostomy, closed as soon as the colorectal anastomosis has healed, is recommended as an alternative to transverse colostomy.", "The aim of this study was to compare loop ileostomy and loop transverse colostomy as the preferred mode of faecal diversion following low anterior resection with total mesorectal excision for rectal cancer.\n Patients who required proximal diversion after low anterior resection with total mesorectal excision were randomized to have either a loop ileostomy or a loop transverse colostomy. Postoperative morbidity, stoma-related problems and morbidity following closure were compared.\n From April 1999 to November 2000, 42 patients had a loop ileostomy and 38 had a loop transverse colostomy constructed following low anterior resection. Postoperative intestinal obstruction and prolonged ileus occurred more commonly in patients with an ileostomy (P = 0.037). There was no difference in time to resumption of diet, length of hospital stay following stoma closure and incidence of stoma-related complications after discharge from hospital. A total of seven patients had intestinal obstruction from the time of stoma creation to stoma closure (six following ileostomy and one following colostomy; P = 0.01).\n Intestinal obstruction and ileus are more common after loop ileostomy than loop colostomy. Loop transverse colostomy should be recommended as the preferred method of proximal faecal diversion.", "The consequences of leakage from low colorectal or coloanal anastomoses are reduced by the use of a loop stoma to divert the faecal stream. Controversy continues as to whether loop ileostomy (LI) or loop transverse colostomy (LTC) is the optimal method of defunctioning such anastomoses.\n Patients requiring defunctioning following anterior resection and total mesorectal excision were randomized to receive either LI or LTC. Comparison was made between the groups regarding the difficulty of stoma formation and closure, the recovery after stoma closure and stoma-related complications. The minimum follow-up after stoma closure was 6 months (median 36 months).\n Between October 1995 and August 1999, 70 patients were randomized (LTC 36, LI 34) of whom 63 underwent stoma closure (LTC 31, LI 32). There were no significant differences in the difficulty of formation or closure, or in the postoperative recovery between the groups. However, there were ten complications related directly to the stoma in the LTC group: faecal fistula (one patient), prolapse (two), parastomal hernia (two) and incisional hernia during follow-up (five). None of these complications occurred in the LI group.\n In this randomized study, the frequency of herniation before or after colostomy closure supports the choice of LI as a method of defunctioning a low anastomosis. Both methods appear to provide satisfactory protection for the low anastomosis." ]

[ "8426316", "11428528", "1564652", "18031818", "21420587", "15465543", "12101459", "18538402", "8201559", "18416260", "20152611", "8733848", "11054329", "15617914", "1630773" ]

[ "Prospectively randomized trial comparing the pseudoaccommodation of the AMO ARRAY multifocal lens and a monofocal lens.", "Contrast sensitivity and depth of focus with aspheric multifocal versus conventional monofocal intraocular lens.", "Multifocal versus monofocal intraocular lenses. Visual and refractive comparisons.", "Comparing the 1CU accommodative, multifocal, and monofocal intraocular lenses: a randomized trial.", "Quality of life evaluation after implantation of 2 multifocal intraocular lens models and a monofocal model.", "Effectiveness of multifocal intraocular lenses to correct presbyopia after cataract surgery: a randomized controlled trial.", "Prospective randomised double-masked trial of bilateral multifocal, bifocal or monofocal intraocular lenses.", "One-year outcomes with new-generation multifocal intraocular lenses.", "Performance of diffractive multifocal intraocular lenses in extracapsular cataract surgery.", "Visual function with bilateral implantation of monofocal and multifocal intraocular lenses: a prospective, randomized, controlled clinical trial.", "Visual function after monocular implantation of apodized diffractive multifocal or single-piece monofocal intraocular lens Randomized prospective comparison.", "Comparison of a diffractive bifocal and a monofocal intraocular lens.", "Cataract extraction with multifocal intraocular lens implantation: a multinational clinical trial evaluating clinical, functional, and quality-of-life outcomes.", "Quality of vision after AMO Array multifocal intraocular lens implantation.", "A prospective, randomized, double-masked comparison of a zonal-progressive multifocal intraocular lens and a monofocal intraocular lens." ]

[ "A prospective trial was set up to compare pseudoaccommodation. Fifty patients were randomized into two groups. Group 1 comprised 25 patients who had a monofocal implant and a postoperative refractive aim of -0.3 to -1.3 diopter (D) spherical equivalent and an astigmatic component between 1.0 and 1.75 D cylinder. Group 2 comprised 25 patients who had a new multizone refraction style multifocal implant and a postoperative refractive aim of -0.5 to +0.5 D spherical equivalent and an astigmatic component of less than 1.0 D cylinder. Eighty percent of postoperative refractions in Group 1 and 88% in Group 2 were within 0.5 D either side of the refractive aim. Forty-eight percent of Group 1 and 72% of Group 2 could see both 20/40 and J3 unaided. Four percent of Group 1 and 84% of Group 2 could read J2 with the distance correction. Sixteen percent of Group 1 and 48% of Group 2 could read J2 at 25 cm unaided (P = .03). Sixty-four percent of Group 1 and 88% of Group 2 stated they could manage daily activities without glasses. However, 88% of Group 1 and 52% of Group 2 requested reading glasses to improve clarity of the smallest print.", "Laboratoires Domilens, Lyon, France, has introduced a new aspheric multifocal intraocular lens (IOL), the Progress 3. The central portion, measuring 4.7 mm in diameter, has an anterior surface of progressively increasing power, such that there is a central add of +5.00 dioptres. We compared contrast sensitivity and depth of focus in patients who received the Progress 3 and in those who received a conventional monofocal IOL.\n Prospective study. Forty patients with age-related cataract were randomly divided into two groups: 20 patients received the Progress 3 aspheric multifocal IOL, and 20 patients received a conventional monofocal IOL of similar design. Contrast sensitivity was measured with the Pelli-Robson letter-based chart. Depth of focus was determined by dialling a series of overcorrections over the patient's manifest refraction until the patient read 6/12 clearly. The depth of focus was defined as the range over which 6/12 or better acuity was achieved. Quality of vision was evaluated by patient questionnaire.\n Mean contrast sensitivity was significantly lower in the patients with a multifocal IOL than in those with a monofocal IOL (1.38 vs. 1.56 log units) (p < 0.001). The mean depth of focus values for the two groups were 3.10 D and 1.65 D respectively (p < 0.001). The prevalence of subjective problems was similar in the two groups.\n In our opinion, aspheric multifocal IOLs should be reserved for patients who are willing to trade increased depth of focus for reduced contrast sensitivity postoperatively.", "In a unilateral prospective clinical trial, 77 cases were randomized to receive a 3M multifocal IOL or a conventional monofocal implant. Multifocal cases had better uncorrected near vision than monofocal cases at the two to four month visit. Thirty percent of the multifocal cases had near acuity J1, while only 4% of the monofocal cases had that acuity. Eighty-seven percent of multifocal cases and 71% of monofocal cases had near acuities of J1 to J3. With distance correction in place, 54% of multifocal cases had near acuities of J1 to J2, while only 28% of monofocal cases had comparable acuities (P = .04). There have been no serious postoperative complications in either group.", "To compare the binocular near vision performance in patients implanted with the 1CU accommodating intraocular lens (IOL) with a multifocal and monofocal IOL.\n Prospective, randomized, double-masked clinical trial.\n Ninety patients presenting for cataract surgery to the Department of Ophthalmology, Hillingdon Hospital were randomized to receive the 1CU accommodative IOL, a multifocal IOL, or a monofocal IOL (control group).\n Patients underwent bilateral sequential phacoemulsification with implantation of 1 of the 3 IOL types and were assessed at 3 and 18 months after second-eye surgery.\n Logarithm of the minimum angle of resolution distance and near visual acuities (VAs) (unaided and distance corrected), contrast sensitivity, and accommodative amplitude (near point and defocusing) were measured at 3 and 18 months. Reading speed was assessed at 18 months, and glare symptoms and spectacle independence were compared using a standardized questionnaire.\n Mean unaided and distance-corrected binocular near VAs were similar in the 1CU and multifocal and were significantly higher than the control group's (P<0.02). There was no significant difference in reading speed between any of the groups, but critical print sizes were similar in the 1CU and multifocal groups and significantly better than the control group's (P = 0.02). The accommodative range was highest in the multifocal group and lowest in the control group, and there was no significant difference between the 1CU and control groups for defocus or near point at 18 months. Of the 1CU group and control group, 71.4% and 63.2%, respectively, experienced no glare at 18 months, compared with only 25% of the multifocal group (P = 0.01). Of the 1CU group and multifocal group, 19% and 27.3%, respectively, were completely spectacle independent at 18 months; none of the control group was (P = 0.05).\n The 1CU accommodating IOL provides improved near vision compared with a monofocal IOL. There is a discrepancy between the near function and accommodative amplitude measured in the 1CU. The multifocal provides excellent near acuity, but photopic phenomena remain a problem inherent in the lens design.", "To compare vision-related quality of life using the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in patients with 1 of 3 types of intraocular lenses (IOLs) and to correlate it with postoperative visual outcomes.\n Vissum Corporation-Instituto Oftalmológico de Alicante, Alicante, Spain.\n Comparative case series.\n This study comprised eyes having cataract surgery with bilateral implantation of a monofocal IOL (Group A), apodized multifocal IOL (Group B), or full diffractive multifocal IOL (Group C). Distance and near visual acuities, contrast sensitivity, and quality of life were evaluated preoperatively and postoperatively.\n The study enrolled 106 eyes (53 patients; age range 49 to 80 years). All groups had significant improvement in uncorrected and corrected distance visual acuities postoperatively (P ≤.05). Near vision outcomes were significantly better in Groups B and C (P ≤.01). Groups B and C had significantly less difficulty in some near tasks, such as reading the newspaper (A-B, P=.02; A-C, P=.02) or reading bills (A-B, P=.04; A-C, P=.004). Group C also had significantly less difficulty driving at night than Group B (P<.01). Near visual acuity and contrast sensitivity were significantly correlated with difficulty in near visual tasks in Groups B and C. Night-driving difficulty correlated significantly with contrast sensitivity in Group B.\n Patients with multifocal IOLs could perform several daily tasks at near and intermediate distances, with less night-driving limitation with the full diffractive IOL than with apodized multifocal and monofocal IOLs.\n No author has a financial or proprietary interest in any material or method mentioned.\n Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.", "Although monofocal intraocular lenses (IOLs) are effective in improving vision after cataract surgery, the loss of accommodation is not restored by implantation of these IOLs. Because multifocal IOLs may improve uncorrected distance and near vision, we compared the clinical outcome and patient satisfaction after implantation of monofocal and multifocal IOLs. Sociodemographics, eagerness for spectacle independence (ESI), and neuroticism were tested as predictors of satisfaction.\n Randomized controlled trial.\n Cataract patients with no ocular comorbidity were operated from August 1999 to January 2001; 75 patients were implanted with monofocal IOLs, and 78 with multifocal IOLs.\n Assessments were made preoperatively (t1), 3 months after first-eye surgery (t2), and 3 months after second-eye surgery (t3). Primary outcomes were obtained by ophthalmic tests, whereas secondary outcomes were examined by interviews.\n Primary outcomes consisted of near and distance visual acuity (VA). Secondary outcomes related to spectacle dependence, vision-related functioning, and patient satisfaction.\n At t3, multifocal IOLs showed significantly better uncorrected near VA than monofocal IOLs (P<0.01) and an increase in quality ratings of unaided near vision between t1 and t3 (on a scale of 1-5: 1.6 at t1 vs. 2.9 at t3, P<0.001). At t2 and t3, patients with multifocal IOLs were more likely to \"never\" or \"only now and then\" wear spectacles for near and distance than patients with monofocal IOLs (at t3, 42.7% multifocal vs. 21.6% monofocal for near [P = 0.002] and 75.0% multifocal vs. 46.2% monofocal for distance [P = 0.001]). On a 0- to 15-point scale, monofocal IOL patients showed fewer complaints from cataract symptoms, including halos and distorted vision, at t3 (1.2 monofocal vs. 2.1 multifocal [P = 0.002]). Satisfaction related to preoperative expectations was similar in the monofocal and multifocal groups. The perceived quality of corrected near vision had the strongest relationship with patient satisfaction (beta = 0.22; 95% confidence interval: 0.060-0.523). Sociodemographics, ESI, and neuroticism did not predict patient satisfaction.\n Overall, patient satisfaction did not differ between the groups of monofocal and multifocal IOLs. Independent of ESI or neuroticism scores, success of both IOLs depends on preoperative expectations and postoperative quality of aided near vision. This article contains additional online-only material available at .", "To evaluate the functional effect of bilateral implantation of two different multifocal intraocular lenses (IOL) compared with the standard monofocal IOL.\n Sixty-nine patients were recruited into a prospective, double-masked, randomised, controlled trial at a single hospital in the United Kingdom. Sixty completed follow-up; 16 implanted with monofocal IOLs, 29 with AMO 'ARRAY' multifocal IOLs and 15 with Storz 'TRUEVISTA' bifocal IOLs. Phacoemulsification and IOL implantation was performed to a standardised technique in both eyes within a 2-month period. The main outcome measures were distance and near visual acuity, depth of field and validated assessment of subjective function (TyPE questionnaire).\n naided distance acuity was good, and equivalent across the three groups. Corrected distance acuity was significantly lower in the bifocal group. Patients with multifocal and bifocal IOLs could read smaller absolute print size than those in the monofocal group (P = 0.05), but at a closer reading distance such that mean unaided near acuity was equal in the three groups. Corrected near acuity was significantly higher in the monofocal control group (P < 0.05). Depth of field was increased in multifocal (P = 0.06) and bifocal (P = 0.004) groups. Overall visual satisfaction was equal in the three groups, while near visual satisfaction was higher in the multifocal group than the monofocal (P = 0.04). Spectacle independence was not seen in the monofocal group, but was achieved in 28% of multifocal IOL patients and 33% of bifocal patients (P < 0.001). Adverse symptoms such as glare and haloes were significantly more bothersome with multifocal (not bifocal) IOLs than monofocals (P = 0.01).\n Multifocal and bifocal IOLs improved unaided near vision performance, with around one in three patients becoming spectacle-independent. The main adverse effect was an increased incidence of subjective glare and haloes in the multifocal IOL group.", "To compare new-generation multifocal intraocular lenses (IOLs) with monofocal IOLs.\n Randomized prospective clinical trial.\n Sixty-two consecutive patients with cataract, seen between January of 2005 and January of 2006 at the Department of Ophthalmology of Palermo University Hospital in Italy, were bilaterally implanted with monofocal (AR 40, Advanced Medical Optics [AMO], Santa Ana, CA; 15 patients), multifocal refractive (Array SA40N, AMO; 16 patients), multifocal refractive (ReZoom, AMO; 15 patients), or multifocal diffractive pupil-independent (Tecnis ZM900, AMO; 16 patients) IOLs.\n Bimanual phacoemulsification.\n Primary outcomes were far, near, and intermediate visual acuity of the 4 IOL-implanted groups. Secondary outcomes were defocusing curves, contrast sensitivity, patients' quality of life (7-item visual function questionnaire [VF-7], halos and glare presence, overall satisfaction), and spectacle independence. Snellen visual acuity was measured as uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), uncorrected near visual acuity (UCNVA), best distance corrected near visual acuity (BDCNVA), best corrected near visual acuity (BCNVA), uncorrected intermediate visual acuity (UCIVA), and best distance corrected intermediate visual acuity (BDCIVA).\n UCNVA was 20/50 in the monofocal IOL group, compared with 20/32 or better in the multifocal IOL groups (P<0.0005). The monofocal IOL group exhibited a lower BDCNVA than the multifocal IOL groups (P<0.0005). The diffractive multifocal IOL group performed better than either refractive group (P = 0.007). UCIVA was significantly different (P = 0.001) among the groups: monofocal (AR 40) 20/32; multifocal refractive (Array SA40N) 20/30; multifocal refractive (ReZoom) 20/25; and multifocal diffractive (Tecnis ZM900) 20/30. Defocusing curves with -3.00 diopter lens exhibited a better trend in the diffractive group. The refractive multifocal IOL groups exhibited lower contrast sensitivities at 3 cycles/degree (P = 0.038). The VF-7 mean score was significantly lower in the monofocal than the multifocal IOL groups (P = 0.002). Night halos were more common in the refractive groups (P<0.01). Spectacle independence was 20% in the monofocal IOL group, 43.7% and 53.3% in the refractive multifocal IOL groups, and 87.5% in the diffractive multifocal IOL group (P<0.05).\n Multifocal IOLs provide a greater depth of focus and higher patient satisfaction, and make intermediate and near visual tasks easier than do monofocal lenses. New-generation, diffractive, pupil-independent multifocal IOLs provide better near vision, equivalent intermediate vision, less unwanted photic phenomena, and greater spectacle independence than either monofocal or refractive multifocal IOLs.", "In a prospective, randomized clinical trial, 42 patients received a monofocal intraocular lens and 38 a multifocal lens after extracapsular cataract extraction. Patients were examined three, six, and 12 months after surgery. Uncorrected visual acuity was 20/40 or better in 57% of monofocal and 58% of multifocal patients; 12% and 52% had near uncorrected visual acuity of J1 to J2, respectively. Best corrected visual acuities were not significantly different. Forty-eight percent of the multifocal and 8% of the monofocal group did not require spectacle correction. On a patient satisfaction questionnaire, 60% of all patients reported discomfort when using spectacles for near vision. Patients in the multifocal group were more satisfied with their near vision than those in the monofocal group. The difference in satisfaction was not significantly different although more multifocal patients reported visual phenomena (e.g., glare, halos). Mean contrast sensitivity for the monofocal group and the multifocal group was 1.73 and 1.70, respectively. At low contrast sensitivities, the difference was not significant although the monofocal patients scored better.", "To evaluate visual function of three types of multifocal intraocular lenses (IOLs) and one monofocal IOL (as the control group) after cataract surgery.\n One hundred fourteen patients participated in a prospective, randomized, controlled clinical study and received monofocal Tecnis Z9000 (AMO) (n = 24, 48 eyes); symmetric diffractive multifocal Tecnis ZM900 (AMO) (n = 26, 52 eyes); zonal refractive multifocal ReZoom (AMO) (n = 32, 64 eyes); and asymmetric diffractive multifocal TwinSet (Acri.Tec) (n = 32, 64 eyes) IOLs.\n Mean binocular distance best spectacle-corrected visual acuity (BSCVA) (logMAR) was 0.05 for controls, 0.08 for ZM900, 0.07 for ReZoom, and 0.11 for TwinSet, with mean binocular distance BSCVA at near of 0.49, 0.06, 0.22, and 0.11, respectively. Mean contrast sensitivity was better for the monofocal IOL group than for the multifocal IOLs. Patients assigned to TwinSet had less favorable contrast sensitivity scores. Patients with monofocal IOLs had more frequently recommended near addition (74%) than those with multifocal IOLs. Patients with refractive ReZoom had also recommended near addition more frequently than the two diffractive groups. The percentage of dysphotopsia phenomena was 81% in patients with diffractive multifocal ZM900 compared with 48% in patients with monofocal IOLs, 53% with refractive ReZoom, and 47% with diffractive TwinSet.\n The monofocal IOL showed better visual function and lesser photic phenomena than multifocal IOLs but patients were spectacle dependent. ReZoom provided better distance BSCVA than the TwinSet diffractive model. Patients with Tecnis and TwinSet diffractive multifocal IOLs were more spectacle independent than patients with ReZoom. Patients with TwinSet had the worst visual function. Patients implanted with the Tecnis diffractive ZM900 were those reporting more photic phenomena.", "To compare visual function after phacoemulsification with implantation of a multifocal intraocular lens (IOL) or a monofocal IOL.\n Department of Ophthalmology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong, China.\n This study comprised patients with unilateral cataract who had phacoemulsification with implantation of an AcrySof ReSTOR SA60D3 multifocal IOL (multifocal group) or an AcrySof SA60AT single-piece monofocal IOL (monofocal group). Postoperative visual function, including uncorrected (UDVA) and corrected (CDVA) distance visual acuity; uncorrected (UNVA), corrected (CNVA), and distance-corrected near visual acuity; and contrast sensitivity were evaluated 1 week, 1 month, and 6 months postoperatively. Patient-reported vision and spectacle independence in the 2 groups were also compared.\n Of the 161 eyes, 72 were in the multifocal group and 89 were in the monofocal group. The multifocal group had statistically significant better UNVA than the monofocal group from 1 week postoperatively to the final follow-up and statistically significant better CNVA at 6 months (both P<.05). There were no statistically significant differences in UDVA or CDVA between the 2 groups over the 6-month follow-up. The multifocal group had statistically significantly better pseudoaccommodation than the monofocal group; the monofocal group had significantly better contrast sensitivity (both P<.05). Patients with the multifocal IOL reported being more satisfied than those with the monofocal IOL.\n The multifocal IOL provided better near visual acuity and more spectacle independence than the monofocal IOL.\n Copyright 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.", "To compare a Pharmacia diffractive bifocal intraocular lens (IOL) with a monofocal lens of the same design without the diffractive grating.\n Multicenter study.\n This randomized, prospective study comprised 70 patients with a monofocal IOL and 79 with a diffractive bifocal IOL. Follow-up was 5 to 6 months. Near and distance visual acuities, contract sensitivity, patient satisfaction, and spectacle use were evaluated.\n All patients achieved a best corrected visual acuity of 0.5 or better; 80% in the monofocal and 71% in the bifocal group had a best corrected visual acuity of 1.0 or better. Without correction, 93% of the bifocal and 9% of the monofocal group could read J3 or better. With distance correction, 99% and 4%, respectively, could read J3 or better. Contrast sensitivity was slightly lower in the bifocal group at distance and near for all spatial frequencies. In the bifocal group, 46% never used spectacles for near tasks. Overall satisfaction was rated good by 86% of the monofocal and 85% of the bifocal group.\n The diffractive bifocal IOL performed well at distance and near. Patients who no longer require spectacles will benefit significantly from a bifocal IOL, but many with a bifocal IOL in one eye will require spectacles for the fellow eye.", "Two million cataract extractions are performed annually in the United States. The procedure is nearly always accompanied by implantation of a monofocal intraocular lens (IOL), which corrects the patient's distance vision. The authors' objective was to measure visual function and quality-of-life outcomes associated with bilateral implantation of a multifocal IOL, which corrects distance and near vision, and to compare the outcomes with those of the standard therapy.\n A prospective, randomized, double-masked, clinical trial was conducted at eight sites in the United States, seven sites in Germany, and one site in Austria.\n Participants included 245 cataract patients, 127 of whom received the multifocal IOL bilaterally and 118 of whom received a monofocal IOL of nearly identical construction bilaterally.\n Clinical data included visual acuity (VA), complications, and adverse events. Quality-of-life data were collected using a previously validated survey instrument at baseline, after first eye surgery, and after second eye surgery.\n At 3 months after surgery, patients who had received multifocal IOLs had significantly better uncorrected and distance corrected binocular near VA compared with patients who had received monofocal IOLs (mean uncorrected VA, 20/26 multifocal vs. 20/40 monofocal; mean distance corrected VA, 20/28 multifocal vs. 20/45 monofocal; P < 0.0001). Additionally, 96% of patients who had received multifocal IOLs and 65% of patients who had received monofocal IOLs achieved both 20/40 and J3 (Jaeger) or better uncorrected, binocular distance and near visual acuities (P < 0. 0001). Patients who had received multifocal IOLs were more likely than patients who had received monofocal IOLs to never wear glasses overall (32% multifocal vs. 8% monofocal; P < 0.0001). On a 4-point scale, patients who had received multifocal IOLs on average reported having between \"a little bit\" and \"some\" glare or halo, whereas patients who had received monofocal IOLs reported between \"none\" and \"a little bit\" of glare or halo (1.57 vs. 0.43; P < 0.001). Patients who had received multifocal IOLs rated their vision without glasses better overall at near and at intermediate distances (P < or = 0.002) and demonstrated better visual function for near tasks and social activities.\n Cataract patients who received multifocal IOLs at time of surgery obtained better uncorrected and distance corrected near VA and reported better overall vision, less limitation in visual function, less spectacle dependency, and more glare or halo than those who received traditional monofocal IOLs.", "To evaluate safety and efficacy of Array SA40N multifocal intraocular lens (IOL) (AMO) implantation in cataract surgery.\n Helsinki University Eye Hospital, Helsinki, Finland.\n In this prospective randomized comparative trial, 80 patients scheduled for cataract surgery were selected based on preoperative counseling and randomized to have multifocal or monofocal IOL implantation. Fifty-three eyes of 35 patients received a multifocal IOL and 67 eyes of 40 patients, a monofocal IOL. The incidence of complications and visual outcome in the multifocal and monofocal IOL groups were compared. Quality of vision was measured by comparing the severity of visual symptoms (glare, halos, and cataract symptoms score), changes in functional impairment measured by a 7-item visual function test (VF-7), changes in global measures of vision (trouble and satisfaction with vision), and range of accommodation and contrast sensitivity.\n Intraoperative and postoperative complications and adverse events were few and required no further surgical intervention. Both distance and near visual acuities were significantly better in the multifocal group than in the monofocal group; the difference was most prominent in distance corrected near acuity (P<.001). Thirty-five eyes (67.3%) in the multifocal group and 10 eyes (14.9%) in the monofocal group achieved a distance corrected near acuity of J6 (20/40) or better; 30 eyes (56.6%) and 19 eyes (28.4%), respectively, achieved a best corrected distance acuity of 20/20 or better. Glare symptoms decreased postoperatively in both groups but were slightly more common in the multifocal group. In contrast, halos were significantly more common at 1 month in the multifocal group (P<.001). Contrast sensitivity values were slightly lower with multifocal IOLs at almost all spatial frequencies, but the difference was not significant. The change in the quality of life postoperatively, measured with the VF-7, was significant and identical in both groups.\n Pseudophakic eyes with multifocal IOLs had better distance and near acuity and range of accommodation than eyes with a monofocal IOL. Slightly lower contrast sensitivity and increased perception of halos by subjects with the multifocal IOL appear to be an acceptable compromise to enhanced near and distance vision.", "Multifocal intraocular lenses (IOLs) have been designed to provide improved near visual acuity without spectacles compared with monofocal IOLs. Early studies have reported variables amounts of decreased visual acuity and contrast sensitivity with multifocal IOLs, and some patients have experienced halos and glare.\n The authors performed a prospective, double-masked, multicenter evaluation of 62 patients randomized between a new zonal-progressive optic multifocal IOL and a monofocal IOL.\n Mean postoperative spherical equivalent, astigmatism, and uncorrected and best-corrected distance visual acuity were similar between the two groups. Patients with a multifocal IOL achieved significantly better uncorrected near visual acuity than patients with monofocal IOLs (J3+ versus J7; P less than 0.0001). With distance correction only, mean near visual acuity was J2 versus J5- (P = 0.0001). Best-corrected near visual acuity was J1 for both groups, with 1.36 diopters (D) for the multifocal group versus 2.37 D for the monofocal group (P less than 0.0001). Regan contrast sensitivity was lower for the multifocal patients at all contrast levels, and achieved statistical significance at very low contrast (11% contrast; P = 0.0024). Fifty-two percent of patients with a multifocal IOL reported that they did not need spectacles at all or used them only for their fellow eye, compared with 25% of the patients with monofocal IOLs.\n Both monofocal and multifocal implant patients were very satisfied with the results of their cataract extraction and IOL implant surgery. A small loss of contrast sensitivity with the multifocal IOL was demonstrated, consistent with theoretical predictions. The functional significance of the loss of contrast sensitivity appears to be small and counterbalanced by the advantage of improved uncorrected near visual acuity." ]

[ "19738090", "19416298", "21507143", "19576090", "18096708", "20097417", "17218551", "20185423", "19493352", "16603606", "14987884", "18852401", "19797133", "19034493" ]

[ "Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial.", "Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial.", "Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia.", "[The value of serum procalcitonin in treatment of community acquired pneumonia in outpatient].", "Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial.", "Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.", "Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy.", "Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection.", "Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial.", "Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial.", "Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial.", "Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care.", "Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study.", "Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study." ]

[ "In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).\n To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.\n A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.\n Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.\n Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.\n The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%).\n In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.\n isrctn.org Identifier: ISRCTN95122877.", "Recent studies have suggested that procalcitonin (PCT) is a safe marker for the discrimination between bacterial and viral infection, and that PCT-guided treatment may lead to substantial reductions in antibiotic use. The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections (LRTIs) in a Danish hospital setting. In a randomized, controlled intervention study, 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis. Patients were randomized to either PCT-guided treatment or standard treatment. Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission. The cut-off point for recommending antibiotic treatment was PCT > or =0.25 microg/L. Physicians could overrule treatment guidelines. The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group (p 0.22). The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average, as compared to 6.8 days in the control group (p 0.007). In a subgroup analysis of chronic obstructive pulmonary disease patients, the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group (p 0.009). It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25% without compromising outcome. No effect on the length of hospital stay was found.", "Use of antibiotics in outpatients with community-acquired pneumonia (CAP) is empirical, which may lead to overuse and selection pressure for resistance. Procalcitonin (PCT) levels may predict the severity of CAP and may be used to guide antibiotic use in hospitalized patients. This study evaluated the value of PCT measurements for guiding antibiotic use in low-risk outpatients with CAP.\n This was a randomized intervention trial conducted between February 2005 and December 2008 that included 172 consecutive patients with suspected CAP, of whom 156 completed the study. The control group received antibiotics according to current guidelines. In the PCT group, antibiotic treatment was based on PCT levels as follows: <0.1 µg/L, strongly discouraged; ≤0.25 µg/L, discouraged; >0.25 µg/L, encouraged. The primary end-points were total antibiotic use and duration of antibiotic treatment; laboratory and clinical outcomes were measured.\n Prescription of antibiotics on admission (84.4% vs 97.5%; P = 0.004), total antibiotic exposure (relative risk 0.55, 95% CI: 0.51-0.60; P = 0.003) and duration of antibiotic treatment (median 5 days vs 7 days; P < 0.001) were reduced in the PCT guidance group, compared with patients treated according to current guidelines. At 4-week follow up, all patients had survived and laboratory and clinical outcomes were similar in the two groups.\n Under PCT guidance, antibiotic use was reduced and duration of antibiotic treatment was shortened in low-risk outpatients with CAP, without apparent harm.\n © 2011 The Authors; Respirology © 2011 Asian Pacific Society of Respirology.", "To evaluate the value of serum procalcitonin (PCT) on antibiotic use in treatment of community acquired pneumonia (CAP) in outpatient.\n From November 2006 to February 2008, a total of 127 patients with CAP in outpatient were randomly assigned into two groups: PCT group (n = 63) and control group (n = 64). PCT levels of all patients were measured after study admission. On the base of similarly normal treatment, the control group received antibiotics according to the attending physicians and the PCT group were treated with antibiotics according to serum PCT levels: antibiotic treatment was applied with PCT level > or = 0.25 microg/L and was discouraged with PCT level < 0.25 microg/L. Clinical efficacy, rate of antibiotics use, duration courses and costs of antibiotics were observed.\n Clinical efficacy of the PCT group was similar with the control group (92.1% vs 87.5%, P > 0.05); rate and costs of antibiotics use was lower, antibiotic duration of the PCT group was shorter than that of the control group (P < 0.05, P < 0.001, P < 0.001).\n PCT could be used in treatment of CAP for antibiotic use in outpatient, which may reduce antibiotic use, shorten antibiotic duration and lower costs of antibiotic.", "The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.\n To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.\n In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.\n Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).\n Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.", "Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.\n In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.\n Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001).\n A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.\n Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations. We evaluated the efficacy and safety of procalcitonin guidance compared to standard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD.\n A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were randomized at the index exacerbation to procalcitonin-guided or standard antibiotic therapy. Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels; standard-therapy patients received antibiotics according to the attending physician. The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months. Secondary outcomes were clinical recovery, symptom scores, length of hospitalization, ICU stay, death, lung function, exacerbation rate, and time to next exacerbation.\n At the index exacerbation, procalcitonin guidance reduced antibiotic prescription (40% vs 72%, respectively; p < 0.0001) and antibiotic exposure (relative risk [RR], 0.56; 95% confidence interval [CI], 0.43 to 0.73; p < 0.0001) compared to standard therapy. Moreover, procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months (RR, 0.76; 95% CI, 0.64 to 0.92; p = 0.004). Clinical outcome and improvement in FEV(1) at 14 days and 6 months did not differ between groups. Within 6 months, the exacerbation rate (0.62 vs 0.64, respectively), the rehospitalization rate (0.21 vs 0.24, respectively), and mean (+/- SD) time to the next exacerbation (70.0 +/- 46.1 vs 70.4 +/- 51.9 days, respectively; p = 0.523) were similar in both groups.\n Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over standard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3.", "Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL(-1). Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73-0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.", "The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients.\n All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to <1 ng/ml or the PCT value was >1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days.\n A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome.\n Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine. ANNOTATION: Results were previously published in German in Anaesthesist 2008; 57: 571-577 (PMID: 18463831).\n ISRCTN10288268.", "In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications.\n To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia.\n In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25 microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome.\n At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%.\n Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.", "Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay.\n 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat.\n Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%).\n Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.", "Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology. A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics. We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day.\n Fifty-three primary care physicians recruited 458 patients, each patient with an acute respiratory tract infection and, in the physician's opinion, in need of antibiotics. Patients were centrally randomized to either a procalcitonin-guided approach to antibiotic therapy or to a standard approach. For patients randomized to procalcitonin-guided therapy, the use of antibiotics was more or less strongly discouraged (procalcitonin level, < or =0.1 or < or =0.25 microg/L, respectively) or recommended (procalcitonin level, >0.25 microg/L). Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers.\n Adjusted for baseline characteristics, the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy (95% confidence interval [CI], -0.53 to 0.81 days), which met our criterion of an increase in days in which activities were restricted by no more than 1 day. With procalcitonin-guided therapy, the antibiotic prescription rate was 72% lower (95% CI, 66%-78%) than with standard therapy. Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days (adjusted odds ratio, 1.0 [95% CI, 0.7-1.5]).\n As an adjunct to guidelines, procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome. In practice, this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics.", "In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.", "Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis.\n Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules.\n The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome.\n Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine." ]

[ "16330868", "17869973", "9894960", "15647576" ]

[ "Safety and therapeutical benefit of hemicraniectomy combined with mild hypothermia in comparison with hemicraniectomy alone in patients with malignant ischemic stroke.", "Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy.", "Mild hypothermia as a protective therapy during intracranial aneurysm surgery: a randomized prospective pilot trial.", "Mild intraoperative hypothermia during surgery for intracranial aneurysm." ]

[ "Both for hemicraniectomy and for hypothermia, several reports describe a beneficial effect in patients with malignant supratentorial cerebral ischemia. We compared the safety and the clinical outcome in patients with a malignant supratentorial infarction who were treated with hemicraniectomy alone (HA) or received a combination therapy with hemicraniectomy and hypothermia of 35 degrees C (HH), respectively.\n In a prospective and randomized study, 25 consecutive patients were treated after an ischemic infarction of more than two thirds of one hemisphere by HA (n=13 patients) or the HH combination therapy (n=12 patients). Safety parameters were compared between both treatment groups, the clinical outcome was assessed during treatment and after 6 months.\n Age, cranial CT or MRI findings, initial National institutes of Health Stroke Scale Score (NIHSSS) and level of consciousness were not significantly different between both groups. Hemicraniectomy was performed within 15+/- 6 h after the ischemic event. Hypothermia was induced immediately after surgery. Overall mortality was 12% (2/13 vs. 1/12 in the two groups), but none of these 3 patients died due to treatment-related complications. There were no severe side effects of hypothermia. Duration of need for intensive care or for mechanical ventilation and infectious status did not differ significantly between both groups, but the need for catecholamine application was increased in the HH group. The clinical outcome showed a tendency for a better outcome in the HH compared with the HA group with respect to status after 6 months, as assessed by the NIHSSS (10+/-1 vs. 11+/-3, p<0.08).\n The present study suggests that a combined therapy of mild hypothermia and hemicraniectomy in malignant brain infarction does not imply additional risks by side effects and improves functional outcome as compared with hemicraniectomy alone.\n Copyright (c) 2006 S. Karger AG, Basel.", "We investigated the effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy (TBI).\n Eighty patients with severe TBI after unilateral craniotomy were randomized into a therapeutic hypothermia group with the brain temperature maintained at 33 degrees C to 35 degrees C for 4 days, and a normothermia control group in the intensive care unit. Vital signs, intracranial pressure, serum superoxide dismutase level, Glasgow Outcome Scale scores, and complications were prospectively analyzed.\n The mean intracranial pressure values of the therapeutic hypothermia group at 24, 48, and 72 hours after injury were much lower than those of the control group (23.49 +/- 2.38, 24.68 +/- 1.71, and 22.51 +/- 2.44 vs 25.87 +/- 2.18, 25.90 +/- 1.86, and 24.57 +/- 3.95 mm Hg; P = .000, .000, and .003, respectively). The mean serum superoxide dismutase levels of the therapeutic hypothermia group at days 3 and 7 were much higher than those of the control group at the same time point (533.0 +/- 103.4 and 600.5 +/- 82.9 vs 458.7 +/- 68.1 and 497.0 +/- 57.3 mug/L, respectively; P = .000). The percentage of favorable neurologic outcome 1 year after injury was 70.0% and 47.5%, respectively (P = .041). Complications, including pulmonary infections (57.5% in the therapeutic hypothermia group vs 32.5% in the control group; P = .025) were managed without severe sequelae.\n Therapeutic mild hypothermia provides a promising way in the intensive care unit for patients with severe TBI after craniotomy.", "To conduct a pilot trial of mild intraoperative hypothermia during cerebral aneurysm surgery.\n One hundred fourteen patients undergoing cerebral aneurysm clipping with (n = 52) (World Federation of Neurological Surgeons score < or =III) and without (n = 62) acute aneurysmal subarachnoid hemorrhage (SAH) were randomized to normothermic (target esophageal temperature at clip application of 36.5 degrees C) and hypothermic (target temperature of 33.5 degrees C) groups. Neurological status was prospectively evaluated before surgery, 24 and 72 hours postoperatively (National Institutes of Health Stroke Scale), and 3 to 6 months after surgery (Glasgow Outcome Scale). Secondary outcomes included postoperative critical care requirements, respiratory and cardiovascular complications, duration of hospitalization, and discharge disposition.\n Seven hypothermic patients (12%) could not be cooled to within 1 degrees C of target temperature; three of the seven were obese. Patients randomized to the hypothermic group more frequently required intubation and rewarming for the first 2 hours after surgery. Although not achieving statistical significance, patients with SAH randomized to the hypothermic group, when compared with patients in the normothermic group, had the following: 1) a lower frequency of neurological deterioration at 24 and 72 hours after surgery (21 versus 37-41%), 2) a greater frequency of discharge to home (75 versus 57%), and 3) a greater incidence of good long-term outcomes (71 versus 57%). For patients without acute SAH, there were no outcome differences between the temperature groups. There was no suggestion that hypothermia was associated with excess morbidity or mortality.\n Mild hypothermia during cerebral aneurysm surgery is feasible in nonobese patients and is well tolerated. Our results indicate that a multicenter trial enrolling 300 to 900 patients with acute aneurysmal SAH will be required to demonstrate a statistically significant benefit with mild intraoperative hypothermia.", "Surgery for intracranial aneurysm often results in postoperative neurologic deficits. We conducted a randomized trial at 30 centers to determine whether intraoperative cooling during open craniotomy would improve the outcome among patients with acute aneurysmal subarachnoid hemorrhage.\n A total of 1001 patients with a preoperative World Federation of Neurological Surgeons score of I, II, or III (\"good-grade patients\"), who had had a subarachnoid hemorrhage no more than 14 days before planned surgical aneurysm clipping, were randomly assigned to intraoperative hypothermia (target temperature, 33 degrees C, with the use of surface cooling techniques) or normothermia (target temperature, 36.5 degrees C). Patients were followed closely postoperatively and examined approximately 90 days after surgery, at which time a Glasgow Outcome Score was assigned.\n There were no significant differences between the group assigned to intraoperative hypothermia and the group assigned to normothermia in the duration of stay in the intensive care unit, the total length of hospitalization, the rates of death at follow-up (6 percent in both groups), or the destination at discharge (home or another hospital, among surviving patients). At the final follow-up, 329 of 499 patients in the hypothermia group had a Glasgow Outcome Score of 1 (good outcome), as compared with 314 of 501 patients in the normothermia group (66 percent vs. 63 percent; odds ratio, 1.14; 95 percent confidence interval, 0.88 to 1.48; P=0.32). Postoperative bacteremia was more common in the hypothermia group than in the normothermia group (5 percent vs. 3 percent, P=0.05).\n Intraoperative hypothermia did not improve the neurologic outcome after craniotomy among good-grade patients with aneurysmal subarachnoid hemorrhage.\n Copyright 2005 Massachusetts Medical Society." ]

[ "3288477", "8836932", "10894991", "10449550", "8665547", "15262734", "10928571", "16211594", "10877152", "1903079", "9270567", "12671949", "10816186", "3076200", "9579296", "2340834", "11248591", "11706112", "9037575", "15330687", "15580607", "7486869", "2208182", "10449123", "9305331", "10210840" ]

[ "A double-blind study of bromocriptine and L-dopa in de novo Parkinson's disease. Short-term results.", "Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study.", "Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson's disease. The French Lisuride Study Group.", "The sydney multicentre study of Parkinson's disease: progression and mortality at 10 years.", "Pramipexole in patients with early Parkinson's disease.", "Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.", "Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease: a two-year follow-up study of previously untreated patients.", "Pergolide versus levodopa monotherapy in early Parkinson's disease patients: The PELMOPET study.", "Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study.", "Dihydroergocryptine in the treatment of Parkinson's disease: a six months' double-blind clinical trial.", "Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group.", "Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.", "A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group.", "Long term bromocriptine treatment in de novo parkinsonian patients.", "A placebo-controlled evaluation of ropinirole, a novel D2 agonist, as sole dopaminergic therapy in Parkinson's disease.", "Long-term double masked trial of early treatment with L-dopa plus bromocriptine versus L-dopa alone in Parkinson's disease. Interim results.", "Levodopa or dopamine agonists, or deprenyl as initial treatment for Parkinson's disease. A randomized multicenter study.", "Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial.", "Early combination of bromocriptine and levodopa in Parkinson's disease: a prospective randomized study of two parallel groups over a total follow-up period of 44 months including an initial 8-month double-blind stage.", "The long-acting dopamine receptor agonist cabergoline in early Parkinson's disease: final results of a 5-year, double-blind, levodopa-controlled study.", "Trial of subtherapeutic pergolide in de novo Parkinson's disease.", "The effect of deprenyl and levodopa on the progression of Parkinson's disease.", "CQA 206-291: a novel dopamine agonist in the treatment of Parkinson's disease.", "Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.", "Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. The Pramipexole Study Group.", "Does combined levodopa and bromocriptine therapy in Parkinson's disease prevent late motor complications?" ]

[ "The first phase of a longitudinal multicenter study comparing bromocriptine and L-dopa (as Sinemet) as de novo therapy for Parkinson's disease using a double-blind randomized design has recently been completed. Over a period of 5.5 months, bromocriptine and L-dopa were equipotent in reducing functional and neurological disability. These observations complement and extend earlier studies and suggest a role for bromocriptine as de novo therapy of Parkinson's disease.", "Long-term levodopa treatment in Parkinson's disease is typically associated with \"motor side effects\" consisting in dyskinesias and/or fluctuations in motility referred to as the on-off phenomena. The main objective of this prospective, randomized, multi-centre study was to determine to what extent the development of such complications could be prevented by partial substitution of levodopa monotherapy (L-DOPA/benserazide) by bromocriptine in patients with early symptoms of the disease. The basic trial population included 674 newly diagnosed Parkinsonian patients that were randomly allocated to monotherapy with levodopa or a combination therapy based upon a nearly 40% replacement of levodopa by bromocriptine. The two target regimens had to be consistently maintained for 42 months. Parkinsonian symptoms were assessed by means of the Webster rating scale, the Hoehn and Yahr scale, and the Zung Self-Rating Depression scale. Motor side effects and adverse events were recorded at each regular clinic visit. Neurological symptoms improved and stabilized in a similar manner during treatment with both regimens throughout the study period. Motor side effects were observed in more patients on levodopa alone than on combination therapy (28.8 vs 20%; p = 0.008). According to Kaplan-Meier estimates the cumulative probability of experiencing motor side effects was 0.43 on monotherapy, compared to 0.28 on combination therapy, which was equal to a one third reduction of risk (p = 0.025). In regard to motor side effects, the degree of substitution of levodopa proved relevant: patients with > 50% substitution by bromocriptine exhibited half the risk observed in those with < 30% (p = 0.045). The overall burden of motor side effects, as reflected by a sum score based upon the relevance, the severity and the extent of motor dysfunction, was also significantly less on combination therapy (p = 0.046). In conclusion, partial substitution of levodopa by bromocriptine (> 30%) as first-line treatment of Parkinson's disease proves active in the prophylaxis of levodopa associated motor side effects. Early combination therapy therefore extends the period of optimal disease control.", "The value of an early initial coadministration of levodopa (L-dopa) and lisuride in Parkinson's disease was the main goal of the present study. Eighty-two patients with recently diagnosed idiopathic Parkinson's disease were randomized into two groups for treatment with L-dopa alone or L-dopa + lisuride. The trial was double-blinded for the first year and open for the following 4 years. Selegiline (10 mg/day b.i.d.) was added in both groups at the end of the first year. Outcome measures were evolution of L-dopa dosage and Unified Parkinson's Disease Rating Scale scores and subscores, and incidence of motor complications. The dropout rate was higher in the L-dopa group (63.4%) than in the combination group. Motor improvement was better (p < 0.01) in the L-dopa + lisuride group. Expected motor complications were rare, moderate and equivalent in the two groups despite a difference in L-dopa dosage (446.7 vs. 387.5 mg/day). Long-term follow-up demonstrated the L-dopa-sparing effect of lisuride (average 1 mg/day), the beneficial effect of early combination therapy on motor status and the paucity of motor complications in both groups.\n Copyright 2000 S. Karger AG, Basel", "To report on a 10 year follow up of patients with idiopathic Parkinson's disease, particularly with respect to mortality and the effect of early treatment with bromocriptine.\n The patients are from the 149 new patients recruited for a double blind, randomised study of low dose levodopa-carbidopa versus low dose bromocriptine. Patients were examined neurologically at least yearly. Neuropsychological examinations were performed at 0, 3, 5, and 10 years. Mortality and cause of death in these patients were compared with the Australian population using standardised mortality ratios (SMRs). Mortality and disease progression were compared by sex and treatment group. Predictors of death within 10 years, nursing home admission, and progression in Columbia score of >/=20 points were examined by logistic regression analysis.\n Thirteen patients were excluded as having atypical Parkinsonism and six were lost to follow up. All available patients have been followed up for 10 years. Fifty patients (38%) were dead by 10 years and 63 by the last follow up. The SMR was 1.58 for all patients (p<0. 001). There was no significant difference in SMRs between the sexes. The mean duration of disease until death was 9.1 years. Parkinson's disease was thought to have contributed substantially to the death of 30 patients. The most common cause of death was pneumonia. Women progressed at a similar rate to men until 8 years, when the severity of their disease as measured by Hoehn and Yahr stage became greater (p<0.05). Older age of onset correlated with increased risk of death but the SMR was increased even in those aged <70 years (SMR 1.80, p=0.03). Early use of bromocriptine did not reduce mortality or slow progression of disease. One quarter of all patients had been admitted to nursing homes by 10 years. Only four patients were still employed.\n Mortality in Parkinson's disease remains increased despite low dose levodopa-carbidopa therapy and no additional benefit was gained from early use of bromocriptine. Duration of disease was similar to that in the era before levodopa.", "We evaluated the efficacy, safety, tolerability, and pharmacokinetics of pramipexole, a novel dopamine D2 receptor agonist, in early Parkinson's disease (PD). The study design was a parallel, placebo-controlled trial using an ascending dose of 4.5 mg/day pramipexole maximum. All subjects received selegiline (10 mg/day) but were not treated with levodopa. Of the 55 subjects who received at least one dose of the study medication, all but one, in the placebo group, completed the trial, which was 9 weeks in duration. The primary efficacy endpoints were changes in scores from baseline to final measurement on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. The pramipexole group had a significantly greater improvement (p = 0.002) than the placebo group on UPDRS Part II (Activities of Daily Living). The change in score from baseline to final measurement on UPDRS Part III (Motor Examination) was not significantly different (p = 0.10) between the pramipexole and placebo groups, although the trend favoured the pramipexole group. All subjects in both the pramipexole and the placebo groups experienced one or more episodes of asymptomatic orthostatic hypotension; there was no significant difference between the pramipexole and the placebo groups in the number of subjects experiencing symptomatic orthostatic hypotension. The adverse events profile of pramipexole was similar, in general, to that of other dopamine receptor agonists. Plasma pramipexole levels increased linearly with dose. Pramipexole appears to be promising agent in the treatment of early PD.", "The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear.\n To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes.\n Multicenter, parallel-group, double-blind, randomized controlled trial.\n Academic movement disorders clinics at 22 sites in the United States and Canada.\n Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001.\n Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability.\n Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events.\n Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups.\n Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.", "The cognitive effects of dopaminergic treatment in Parkinson's disease (PD) are still controversial.\n To evaluate, in previously untreated patients with PD, whether chronic dopaminergic stimulation produces significant cognitive changes; whether they are sustained beyond the period of a few months; and whether the cognitive status of two motor-comparable groups is differently affected by levodopa and pergolide.\n Parallel, randomized open study with blind neuropsychologic evaluation of 20 consecutive de novo patients with PD before and 3, 6, 12, 18, and 24 months after monotherapy with levodopa (n = 10) or pergolide (n = 10; 6-month monotherapy; pergolide + levodopa thereafter).\n Both treatments were associated with a significant improvement in motor scores and in tests assessing learning and long-term verbal and visual memory, visuospatial abilities, and various frontal tasks. While improvement in motor scores persisted, improvement in activities of daily living and in semantic fluency, Luria's rhythm and motor and long-term memory tests was not sustained at the 24-month examination. Further, performance on attentional, short-term memory, and the Stroop tests did not change over the course of the study.\n Both treatments were associated with incomplete but long-lasting (18 mos) improvement in many cognitive tasks which declined thereafter, suggesting that dopaminergic replacement is not enough to compensate for all cognitive deficits of PD.", "Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing \"rescue\" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa \"rescue\" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.\n (c) 2005 Movement Disorder Society.", "A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable.\n Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample.\n The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, alpha-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, alpha-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (alpha-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of alpha-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between alpha-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent.\n The results indicate that alpha-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients.", "The short-term efficacy of dihydro-alpha-ergocryptine (DEK), a hydrogenate ergot derivative with dopamine (DA) agonist properties was evaluated in 20 L-dopa (LD) stable responder parkinsonian patients by a 6-month double-blind randomized, placebo-controlled study. A motor improvement was found only in DEK-treated patients at mean daily doses of approximately 40 mg, ranging from 15 to 60 mg. The side effects never required the withdrawal of the drug or changes in its schedule. The authors demonstrate the efficacy and the good tolerability of DEK as a new DA agonist drug that can be added to LD in the treatment of parkinsonian patients.", "A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.", "Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients.\n Copyright 2003 Movement Disorder Society", "There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist.\n In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia.\n Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements).\n Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.", "nan", "The efficacy and safety of ropinirole, a novel nonergot dopamine D2-like receptor agonist, was assessed as monotherapy for the treatment of patients with early-stage Parkinson's disease. In this double-blind, multicenter trial, patients were randomly allocated in a ratio of 2:1 to receive, over a 12-week period, either ropinirole or placebo. Clinical status was assessed using the Unified Parkinson's Disease Rating Scale (UP-DRS), Clinician's Global Evaluation (CGE), and a finger-tapping score. In all, 41 patients received ropinirole and 22 received placebo. The end-point analysis, on an intention-to-treat basis, revealed a significant difference (p = 0.018) in improvement in UP-DRS motor score from baseline between treatment groups (ropinirole, 43.4%; and placebo, 21.0%). Other parameters, including the number of responders and improvement in CGE, showed similar results. Three patients in the ropinirole group and one patient in the placebo group discontinued the study because of adverse events. There was no significant difference between the treatment groups in the overall incidence of adverse events. Although the dopaminergic side effects were reported significantly more frequently in the ropinirole group than in the placebo group (dizziness, p = 0.0326; nausea, p = 0.001; and somnolence, p = 0.005), none necessitated study withdrawal. There was no evidence of any chronic effect of the study medication on vital signs. In conclusion, ropinirole is a safe and well-tolerated drug and, as monotherapy, provided significant therapeutic benefit compared with placebo to patients in the early stages of Parkinson's disease.", "The quality and duration of control in two groups of parkinsonian patients under treatment with an L-dopa-based drug alone or L-dopa-based drug which has been partially substituted with bromocriptine are being compared over a 5-year period using a double-blind placebo-controlled study design. The aim is to establish whether early addition of bromocriptine will minimise late L-dopa complications. Results are presented after 1 year. Of 31 patients randomised, 13 were treated with combined L-dopa/bromocriptine and 14 with L-dopa/placebo. 4 patients were withdrawn for various reasons. In both groups any dose adjustments were aimed at maintaining the pre-entry clinical condition. In the group receiving bromocriptine combination therapy, progressive reduction of L-dopa was possible without deterioration of the patients' condition. In patients receiving L-dopa alone, the dose of L-dopa at 12 months was almost similar to that recorded on entry to the study. The total number of patients reporting adverse events in the L-dopa/bromocriptine combination and L-dopa alone groups were 8 and 7, respectively. At the present interim stage of the study it is not possible to compare the incidence of L-dopa long-term complications in either group.", "Objectives: levodopa improves the quality of life in parkinsonian patients, however long term response is compromised by the emergence of motor fluctuations and dyskinesias. The aim of this study was to compare the occurrence of motor fluctuations and dyskinesias in previously untreated patients assigned to receive levodopa, a dopamine agonist or deprenyl.Thirty-five neurological departments in Italian hospitals participated in this randomized open trial. Patients with Parkinson's disease, who required the initiation of an effective antiparkinsonian treatment, were randomly assigned to receive levodopa, dopamine agonists or deprenyl. The end-points were motor dyskinesias and motor fluctuations occurring in a median follow-up period of about 3years.After a median follow-up of 34months, motor fluctuations and dyskinesias were less frequent in patients assigned to a dopamine agonist or deprenyl than in patients assigned to levodopa (relative risk [RR] 0.5, 95% confidence interval [95% CI] 0.3-0.8, and RR=0.6, 95% CI 0.3-0.9, respectively), but dopamine agonists were less effective and less well tolerated than levodopa. The lower frequency of motor fluctuations in patients assigned to deprenyl was no longer statistically significant when prognostic predictors were considered in a multivariable analysis. Long-term mortality did not differ in the three arms of the study. Dopamine agonists and deprenyl can be considered as an alternative to levodopa for starting treatment in Parkinson's disease patients. However, on clinical grounds, only small advantages are expected over the traditional therapy initiation with levodopa.", "The long-term effectiveness of three different initial drug regimes in patients with early, mild PD was evaluated by the PD Research Group of the United Kingdom (PDRGUK). In 1995, the selegiline arm of the trial was terminated following an interim analysis.\n This was an open, randomized trial. Between 1985 and 1990, 782 patients with de-novo PD were recruited and randomized to one of three treatment arms: levodopa plus dopa decarboxylase inhibitor; levodopa plus decarboxylase inhibitor and selegiline; or bromocriptine. The main endpoints were mortality, disability, and adverse events. Intention-to-treat analysis was used.\n There was no significant difference in mortality between the bromocriptine and the levodopa arms (hazard ratio 1.15 [95% CI 0.90, 1.47]). Patients initially randomized to bromocriptine had slightly worse disability scores throughout follow-up. This difference was significant during the first years. Patients in the bromocriptine arm returned to pretreatment disability levels one year earlier than those in the levodopa arm. Patients randomized to bromocriptine had a significantly lower incidence of dyskinesias than those randomized to levodopa (rate ratio 0.73 [95% CI 0.57, 0.93]). However, this difference was not significant when only moderate to severe dyskinesias were considered. Patients in the bromocriptine arm had slightly lower rates of dystonias and on-off fluctuations, but moderate and severe forms were equally frequent in both arms.\n Starting treatment with the dopamine agonist bromocriptine does not reduce mortality in PD. A slightly lower incidence of motor complications is achieved at the expense of significantly worse disability scores throughout the first years of therapy.", "To determine if the combination of levodopa (LD) plus bromocriptine (Br) in the early stages of Parkinson's disease (PD) permits reduction of LD dosage and consequently results in fewer motor fluctuations and dyskinesias, a double-blind, multicenter prospective study in 50 PD patients who had responded favorably to LD while under treatment with that drug for < or = 6 months was undertaken. Patients were randomized into two parallel groups (LD alone and LD plus Br). During the first placebo-controlled stage of the study lasting 8 months, association of a fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant reduction in the daily LD dose. Still, in patients on combined LD plus Br, there was a tendency toward smaller daily requirements of LD as compared with those on LD alone, and the difference in LD dose between the two groups was significantly different (515.4 +/- 240 vs. 725.6 +/- 230 mg/day; p < 0.01) after 44 months of continuous treatment in the 40 patients still enrolled in the open-label stage. At that point in time, the mean dose of Br had been increased by 9.2 mg in the combined treatment group, and the mean dose of LD was 40.7% lower than in the group receiving LD alone. On subsequent evaluations, the number of patients with dyskinesias or describing wearing-off fluctuations severe enough to require changes in treatment was lower than in the group under combined therapy, the differences being significant after 20 and 44 months, respectively (36.8 vs. 9.5 and 47.3 vs. 14.2%). Our results support early combined LD-Br therapy in PD, but no conclusions can be drawn as to whether this dopamine agonist exerts a preventive effect on the late side effects of LD or has another mechanism of action.", "Cabergoline is an ergoline derivative with a very long half-life that allows once-daily administration and the potential for more continuous stimulation of dopaminergic receptors than is possible with other dopamine receptor agonists (DAs). The aim of this study was to evaluate whether the possible advantage resulting from a more sustained dopaminergic effect of cabergoline would translate into delayed onset of motor complications, compared with levodopa, in patients with newly diagnosed Parkinson's disease.\n This study was a double-blind, multicentre trial that compared cabergoline and levodopa as initial therapy for Parkinson's disease. A total of 419 levodopa-, DA- and selegiline-naive patients with newly diagnosed Parkinson's disease were randomised to receive either cabergoline (n = 211) or levodopa (n = 209). Treatment was titrated to an optimal dose over a period of up to 24 weeks and then continued at this dose until the study endpoint (confirmed motor complications) or up to a maximum of 5 years. At years 1-5, the cabergoline group was receiving cabergoline at average daily doses ranging from 2.8-2.9 mg, with added levodopa at mean daily doses ranging from 322 mg at year 1 to 431 mg at year 5; over the same period, the levodopa group was receiving daily levodopa doses of 784 mg. Thus, patients in the cabergoline group received <50% levodopa than patients in the levodopa group.\n Motor complications were significantly delayed (p = 0.0175) and occurred less frequently in cabergoline-treated patients than in levodopa-treated patients (22.3% vs 33.7%). Cox model proportional hazards regression analysis showed that the relative risk of developing such complications was >50% lower (0.46; p < 0.001) in the cabergoline group compared with the levodopa group. In particular, development of dyskinesias was markedly delayed in the cabergoline group and occurred in 9.5% of patients compared with 21.2% in the levodopa group (p < 0.001). Among patients not requiring supplemental levodopa, the frequency of motor complications was three times higher with levodopa (15.5% of 110 patients) than with cabergoline (5.3% of 76 patients). Among patients who did need supplemental levodopa, motor complications were more frequent in the levodopa arm (54.1% of 98 patients) than in the cabergoline arm (31.9% of 135 patients). Consistent improvements relative to baseline in average Unified Parkinson's Disease Rating Scale (UPDRS) daily living activities and motor function sections, and in Clinical Global Impression severity of illness and physician- and patient- rated global improvement scores, were seen in both treatment groups, with maximal effects occurring within 2 years. However, levodopa treatment was associated with a significantly (p < 0.001) greater improvement in motor disability (as measured by the UPDRS motor score) over time, with mean values of 13.8 versus 12.9 in the cabergoline versus levodopa arm recorded at 1 year, 18.6 versus 17.2 at 3 years and 19.2 versus 16.3 at 5 years, respectively. While the overall frequency of adverse events was similar in the two groups, the cabergoline-treated group experienced marginally, but not significantly, higher frequencies of nausea, vomiting, dyspepsia and gastritis (37.4% vs 32.2% in the levodopa group) and of dizziness and postural hypotension (31.3% vs 24% in the levodopa group). Cabergoline-treated patients also experienced a significantly higher frequency of peripheral oedema (16.1% vs 3.4%, respectively; p < 0.0001). The cabergoline and levodopa groups had similar rates of sleepiness (17.5% vs 18.3%, respectively) and hallucinations (4.8% vs 4.4%, respectively); in an elderly population subset, hallucinations were reported in 7.1% and 6.5% of patients taking cabergoline and levodopa, respectively. Adverse events generally occurred more frequently in female patients (with the exception of dyskinesias, hyperkinesias and hallucinations, which occurred more frequently in men) and in the elderly.\n This study showed that, compared with levodopa, initial therapy with cabergoline in patients with Parkinson's disease is associated with a lower risk of response fluctuations at the cost of a marginally reduced symptomatic improvement and some tolerability disadvantages that are mostly limited to a significantly higher frequency of peripheral oedema.", "The effect of pergolide 25 mug twice daily on levodopa initiation was assessed in a randomized, placebo-controlled, parallel group, double-blind multicenter trial in 106 untreated early Parkinson's disease patients. The primary endpoint of mean time until levodopa was 520 days (95% confidence interval [CI], 422-618 days) for pergolide versus 434 days (95% CI, 358-609 days) for placebo. However, this increase of 86 days for pergolide was not statistically significant. The wash-in effect of pergolide was significant at 6 weeks (change in mean Unified Parkinson's Disease Rating Scale [UPDRS] 2 and 3 was -0.1 [95% CI, -1.4 to 1.3] for pergolide vs. 2.2 [95% CI, 1.1-3.3] for placebo). At termination, the change from baseline in mean UPDRS 2 and 3 score was 11.4 (95% CI, 8.8-14) for pergolide and 14.6 (95% CI, 12-17.2) for placebo (P=0.08). There was no significant change in UPDRS 2 and 3 for the 83 patients achieving the planned 4-week washout at termination (pergolide 1.2 [95% CI, -0.8 to 3.2] vs. placebo 0.0 [95% CI, -1.6 to 1.6]. Adverse events were infrequent and occurred equally for pergolide and placebo. The study shows no evidence of a neuroprotective effect but indicates a mild symptomatic benefit from pergolide at a dose normally considered subtherapeutic.", "We have performed a 14-month, prospective, randomized, double-blind, placebo-controlled study to evaluate the effect of deprenyl and levodopa/carbidopa (Sinemet) on the progression of signs and symptoms in patients with mild Parkinson's disease (PD). One hundred one untreated PD patients were randomly assigned to one of the following four treatment groups: Group I, deprenyl + Sinemet; Group II, placebo-deprenyl + Sinemet; Group III, deprenyl + bromocriptine; and Group IV, placebo-deprenyl + bromocriptine. The final visit was performed at 14 months, i.e., 2 months after withdrawal of deprenyl or its placebo and 7 days after withdrawal of Sinemet or bromocriptine. Deterioration in Unified Parkinson's Disease Rating Score (UPDRS) between untreated baseline and final visits was used as an index of disease progression. Placebo-treated patients deteriorated by 5.8 +/- 1.4 points, while deprenyl-treated patients deteriorated by 0.4 +/- 1.3 points (p < 0.001). This effect was sufficiently powerful that a significant deprenyl effect could be detected in the subgroup of 41 patients randomized to Sinemet (p < 0.01) as well as in the 23 patients who completed a 14-day washout of Sinemet or bromocriptine (p < 0.05). No difference in the extent of deterioration was detected in patients randomized to Sinemet versus bromocriptine. This study demonstrates that deprenyl attenuates deterioration in UPDRS score in patients with early PD. These findings are not readily explained by the drug's symptomatic effects and are consistent with the hypothesis that deprenyl has a neuroprotective effect.", "The antiparkinsonian efficacy and tolerability of CQA 206-291, a novel ergoline derivative with potent dopamine agonist properties, were studied during 2 months of treatment in 72 parkinsonian patients. In 36 de novo patients (patients who have not previously been treated with levodopa or dopamine agonists), CQA 206-291 was studied in an open design, while in 36 levodopa-treated patients, CQA 206-291 was studied in a randomized, double-blind, parallel-group, placebo-controlled design. CQA 206-291 induced in both groups a significant antiparkinsonian effect with an effective dose range of 5-30 mg/day. The spectrum of adverse events was similar to what is commonly observed with dopamine agonists. Further studies are required to assess the putative therapeutic advantages of CQA 206-291 when compared to other antiparkinsonian drugs.", "To determine whether pergolide monotherapy provides symptomatic relief in early PD.\n Early treatment with dopamine agonists may reduce the risk of motor fluctuations, which are most likely linked to levodopa therapy. Pergolide, a D1-D2 dopamine agonist, has been studied as \"add on\" therapy in PD, but no controlled clinical trial studying the efficacy of pergolide monotherapy is available.\n The efficacy and tolerability of pergolide were evaluated in a multicenter, double-blind, randomized, parallel-group, 3-month trial versus placebo. Patients with a diagnosis of idiopathic PD, a modified Hoehn & Yahr score of 1 to 3, and a score greater than 14 points on the Unified Parkinson's Disease Rating Scale (UPDRS) part III at baseline were enrolled in the study (pergolide, n = 53; placebo, n = 52).\n Patient characteristics at study entry were comparable in the two study groups. The pergolide group showed a significantly greater percent of responders (defined as a -30% decrease in UPDRS part III score at end point) compared with placebo (57% versus 17%; p < 0.001). Pergolide-treated patients experienced a significantly greater improvement than placebo-treated patients (p < 0.001) in UPDRS (overall, part II, and part III) score, Schwab & England score, and Clinical Global Impression improvement score. By the study end the mean dose of pergolide was 2.06 mg/day. Six patients in the pergolide group versus two patients in the placebo group discontinued the study because of treatment emergent side effects.\n This study suggests that pergolide monotherapy may be an efficacious and well-tolerated first-line treatment in patients with early-stage PD.", "A total of 335 patients with early Parkinson's disease (PD) were enrolled in a multicenter, randomized, double-blind trial designed to assess the efficacy and safety of pramipexole. Entry was restricted to patients with idiopathic PD who were not receiving levodopa. Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication. This was followed by a 24-week period of maintenance therapy. The mean daily dose during the maintenance period was 3.8 mg. Pramipexole significantly reduced the severity of PD symptoms and signs compared with placebo, as measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale at week 24 compared with baseline (p < or = 0.0001). Differences between the active drug and placebo groups emerged at week 3 (1.5 mg/d) in the ascending-dose interval and persisted throughout the maintenance phase (p < or = 0.0001). The majority of patients completed the study (pramipexole 83%, placebo 80%). In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients. No clinically significant changes were noted in blood pressure or pulse rate. Overall, these results indicate that pramipexole is safe and effective in the treatment of early PD.", "Levodopa-carbidopa (LD) in low dosages adequately controls symptoms in most patients with Parkinson's disease and delays the appearance of fluctuations and dyskinesias. It has been suggested that early combination therapy with bromocriptine and levodopa delays or prevents the onset of late treatment complication associated with LD monotherapy in Parkinson's disease. We have conducted this study to assess the possible benefit of combined therapy compared with levodopa monotherapy. Seventy-eight previously untreated patients with Parkinson's disease were recruited over a period of 54 months and randomly allocated to either a levodopa-carbidopa (LD) Group or a levodopa-carbidopa in combination with low-dose bromocriptine (LD-Br) Group. The appearance of motor complications determined the end point of the study. We gradually increased the doses of bromocriptine (2.5-15 mg/d) or levodopa (125-500 mg/d) until the maximum \"on\" time was reached. In six patients, the doses of levodopa had to be increased up to the optimal dose (625-1000 mg/day). In the last evaluation the on-time and parkinsonian disability were similar in both treatment groups. We did not find statistically significant differences in the frequency of motor complications when comparing the two groups of treatment. Our study suggests that early combination of levodopa and bromocriptine does not confer any clinical benefit over levodopa alone in treating early Parkinson's disease, nor will it influence the evolution of the disease.Copyright Lippincott-Raven Publishers" ]

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[ "L-phenylalanine and UVA irradiation in the treatment of vitiligo.", "A randomized, placebo-controlled, double-blind trial comparing narrowband UV-B Plus 0.1% tacrolimus ointment with narrowband UV-B plus placebo in the treatment of generalized vitiligo.", "[Evaluation of an antioxidant and mitochondria-stimulating cream formula on the skin of patients with stable common vitiligo].", "Ultraviolet A in vitiligo.", "Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo.", "Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS).", "A randomized placebo-controlled double-blind study of levamisole in the treatment of limited and slowly spreading vitiligo.", "Randomized, double-blind clinical trial to evaluate the efficacy of topical tacalcitol and sunlight exposure in the treatment of adult nonsegmental vitiligo.", "Double-blind placebo-controlled study of autologous transplanted epidermal cell suspensions for repigmenting vitiligo.", "Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12.", "Comparison of systemic PUVA and NB-UVB in the treatment of vitiligo: an open prospective study.", "A comparative study of punch grafting followed by topical corticosteroid versus punch grafting followed by PUVA therapy in stable vitiligo.", "Comparison of melanocytes transplantation methods for the treatment of vitiligo.", "Safety and therapeutic effectiveness of 8-methoxypsoralen, 4,5',8-trimethylpsoralen, and psoralen in vitiligo.", "Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study.", "Topical tacalcitol and 308-nm monochromatic excimer light: a synergistic combination for the treatment of vitiligo.", "Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial.", "A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo.", "Combination of 308-nm xenon chloride excimer laser and topical calcipotriol in vitiligo.", "Comparison of minipunch grafting versus split-skin grafting in chronic stable vitiligo.", "Clinical observation on the effect of Zengse Pill in treating patients with vitiligo of qi-stagnancy and blood-stasis syndrome type.", "Comparison of 0.05% clobetasol propionate cream and topical Puvasol in childhood vitiligo.", "Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo.", "Vitiligo and intralesional steroids.", "Systemic immunomodulatory effects of Polypodium leucotomos as an adjuvant to PUVA therapy in generalized vitiligo: A pilot study.", "Combination of PUVAsol and topical calcipotriol in vitiligo.", "Effect of one session of ER:YAG laser ablation plus topical 5Fluorouracil on the outcome of short-term NB-UVB phototherapy in the treatment of non-segmental vitiligo: a left-right comparative study.", "Left-right comparison study of the combination of fluticasone propionate and UV-A vs. either fluticasone propionate or UV-A alone for the long-term treatment of vitiligo.", "Efficacy of autologous transplantation of noncultured epidermal suspension in two different dilutions in the treatment of vitiligo.", "Efficacy and safety of pimecrolimus cream 1% in adult patients with vitiligo: results of a randomized, double-blind, vehicle-controlled study.", "Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study.", "Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients.", "Randomized controlled trial comparing the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in the treatment of vitiligo of the face and neck.", "Treatment of vitiligo with topical 15% lactic acid solution in combination with ultra violet-A.", "Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study.", "Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index.", "The efficacy of pimecrolimus 1% cream plus narrow-band ultraviolet B in the treatment of vitiligo: a double-blind, placebo-controlled clinical trial.", "Effect of topical calcipotriol, betamethasone dipropionate and their combination in the treatment of localized vitiligo.", "The efficacy of combined PUVA and low-dose azathioprine for early and enhanced repigmentation in vitiligo patients.", "An open labeled, comparative clinical study on efficacy and tolerability of oral minipulse of steroid (OMP) alone, OMP with PUVA and broad / narrow band UVB phototherapy in progressive vitiligo.", "Comparison between 308-nm monochromatic excimer light and narrowband UVB phototherapy (311-313 nm) in the treatment of vitiligo--a multicentre controlled study.", "Targeted broadband ultraviolet b phototherapy produces similar responses to targeted narrowband ultraviolet B phototherapy for vitiligo: a randomized, double-blind study.", "The treatment of vitiligo with psoralens and triamcinolone by mouth.", "Topical tacrolimus and the 308-nm excimer laser: a synergistic combination for the treatment of vitiligo.", "Comparison of two surgical approaches for treating vitiligo: a preliminary study.", "Tacalcitol and narrow-band phototherapy in patients with vitiligo." ]

[ "In order to evaluate the efficacy of L-phenylalanine (L-Phe) in combination with UVA therapy for vitiligo an open trial (149 patients, 18 months) and a small double-blind trial (32 patients, 6 months) were conducted. Oral L-Phe loading resulted in peak plasma levels of L-Phe after 30-60 min and a slight increase in the plasma tyrosine level. Response to L-Phe plus UVA irradiation was positive, and various grades of repigmentation not exceeding 77% in the open and 60% in the blind trial were observed. An increased L-Phe dose resulted in increased L-Phe plasma levels but not in improved clinical results. The optimal L-Phe dose appears to be lower than 50 mg/kg/day. Although it is difficult to draw firm conclusions from the present investigation, we think that L-Phe may have a place in the treatment of vitiligo and its role merits further investigation.", "nan", "Vitiligo is a chronic illness of a yet unknown etiology, characterized by an acquired and progressive depigmentation of the skin. There are diverse treatments for this condition around the world, but up to now, none has been completely effective. The objective of this work was to evaluate the application of an antioxidant and mitochondrial stimulating formula, of topic use in leukodermic areas of patients with stable vulgar vitiligo. A clinical, experimental, randomized, double blind study was carried out in 50 male and 50 female patients with stable vulgar vitiligo. The patients were distributed in five groups as follows: Group 1 (labelled as VitilVenz AF): application of antioxidant and mitochondrial stimulating cream and oral administration of antioxidants and phenylalanine. Group 2 (labelled as Placebo AF): application of a placebo cream and oral administration of antioxidants and phenylalanine. Group 3 (labelled as without cream AF): oral administration of antioxidants and phenylalanine. Group 4 (labelled as Placebo cream): application of a placebo cream. Group 5 (labelled as VitilVenz): application of the antioxidant and mitochondrial stimulating cream. The following were measured in all patients: the clinical area of newly formed pigment every 30 days, during five months; and the presence of melanocytes in the histological study, at the beginning and at the end of treatment. The test of multiple comparison of Turkey-Kramer was used for the analysis of the results. The scheme of treatment that produced the best results was that of the Group 1, which consisted of the joint application of the antioxidant and mitochondrial stimulating cream and oral administration of antioxidants and phenylalanine (p < 0.001); followed by Group 5 that only received the topical treatment with the antioxidant and mitochondrial stimulating cream. The clinical and histological responses of these two groups (1 and 5) were significantly different to the rest of the groups. We concluded that the melanocytes in these patients could be in a dysfunctional state, product of the formation of free radicals that cause cellular and mitochondrial toxicity; and that these free radicals are removed by the antioxidant and mitochondrial stimulating elements present in the cream, turning the melanocytes functional and producing melanin in the achromic area of the vitiligo. This effect would be potentiated by the use of oral antioxidants and phenylalanine.", "Both types of Ultraviolet (UV), UVB (290-320 nm) and UVA (320-400 nm), produce increased pigmentation or tanning. However, no evaluation of UVA alone in the treatment of vitiligo has been reported. Therefore, it was the purpose of this work to study the pigmentogenic effect of UVA (5 and 15 J/cm(2)) in vitiligo. The study included 20 randomly selected patients with vitiligo involving more than 30% of the body surface area with a bilateral/symmetrical distribution. They were equally divided into two groups each of 10 patients. All patients received three weekly sessions of UVA, 15 J/cm(2) in group I and 5 J/cm(2) in group II, a total of 48 sessions over 16 weeks. Overall pigmentation of 60% and above was recorded in 50% and 10% of patients in groups I and II, respectively. We conclude that broadband UVA alone, without psoralens, and in appropriate doses may be of important therapeutic value in vitiligo.", "For effective treatment of vitiligo, it is as important to arrest the progression of the disease as it is to induce repigmentation. Recently, oxidative stress has been shown to play an important role in the pathogenesis of vitiligo. Ginkgo biloba extract has been shown to have antioxidant and immunomodulatory properties. In a double-blind placebo-controlled trial, we evaluated the efficacy of G. biloba extract in controlling the activity of the disease process in patients with limited and slow-spreading vitiligo and in inducing repigmentation of vitiliginous areas. Fifty-two patients were assigned to two treatment groups (A and B) in a double-blind fashion, but only 47 patients could be evaluated, because one patient in group A and four patients in group B withdrew for reasons unrelated to the study. Patients in group A were given G. biloba extract 40 mg three times daily whereas patients in group B received placebo in similar doses. A statistically significant cessation of active progression of depigmentation was noted in patients treated with G. biloba (P = 0.006). Marked to complete repigmentation was seen in 10 patients in group A, whereas only two patients in group B showed similar repigmentation. The G. biloba extract was well tolerated. G. biloba extract seems to be a simple, safe and fairly effective therapy for arresting the progression of the disease.", "Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment. There is now in vivo evidence for increased epidermal hydrogen peroxide (H(2)O(2)) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy (FT Raman). Epidermal H(2)O(2) can be removed with a topical application of narrow band UVB activated pseudocatalase cream (PC-KUS). (Mn/EDTA-bicarbonate complex, patent No. EPO 58471 1 A), yielding initiation of repigmentation. Dead Sea climatotherapy is another successful treatment modality for vitiligo, but the mode of action has escaped definition so far.\n Epidermal hydrogen peroxide (H(2)O(2)) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy. The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream (PC-KUS) as well as Dead Sea climatotherapy/placebo cream. Clinical repigmentation was documented by standardized black/white photography using non-UV coated bulbs as flashlight and by color photography.\n This study on 59 patients who had vitiligo for an average time of 17 years (range 3-53 years) confirmed in vivo H(2)O(2) accumulation in mM concentrations in the epidermis of untreated patients. Furthermore, we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing, but the decrease of epidermal H(2)O(2) levels was significantly less compared to narrowband UVB activated pseudocatalase cream (PC-KUS). Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy (8-14 weeks) and Dead Sea climatotherapy alone (5-6 weeks).\n The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy (21 days) at the Dead Sea in combination with a pseudocatalase cream (PC-KUS) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy. This combined therapy is significantly faster in repigmentation than narrowband UVB activated pseudocatalase cream (PC-KUS) treatment alone. The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo.", "A previous uncontrolled, open trial of levamisole in patients with limited and slowly spreading vitiligo had shown that new lesions did not develop in 94% of patients after 2-4 months of treatment with the drug.\n To assess the efficacy of levamisole in the treatment of slowly spreading, limited vitiligo.\n In a randomized double-blind trial at the Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India, 60 patients with vitiligo involving < 2% of the body surface area and with slowly spreading disease (defined as one to five new lesions in the previous month or six to 15 new lesions in the previous 3 months) were randomly allocated to receive oral levamisole 150 mg or placebo on two consecutive days in a week. Children received oral levamisole 100 mg. All patients applied mometasone furoate 0.1% cream on the depigmented macules once daily. Patients were evaluated monthly for 6 months. The main outcome measure was the occurrence of new lesions, counted at each monthly visit. The secondary outcome measures comprised: (i) a dermatology-specific instrument, the Dermatology Life Quality Index or Children's Dermatology Life Quality Index questionnaires, which were completed by the patients at baseline and at every visit, and (ii) a general health questionnaire, the World Health Organization Quality of Life Brief Questionnaire, which was completed at baseline and at the end of the study.\n Forty-three patients completed 6 months of follow-up. The mean +/- SD number of new lesions that developed during the study period of 6 months was 1.9 +/- 2.0 (range 0-8) in the levamisole group and 1.8 +/- 2.0 (range 0-7) in the placebo group (P = 0.92). The proportion of patients who did not develop any further new lesions for the remainder of the study period was higher in the levamisole group at all the monthly evaluation points, although it was statistically significant (P = 0.05) only at the fourth month. Improvement in quality of life was similar in both groups.\n The study indicates that levamisole is not as effective in arresting disease progression as was observed in a previous open study. A study with a larger sample size is necessary to determine if levamisole is truly superior to placebo in this respect.", "Vitiligo is a common skin disease which is difficult to treat. Approximately half of patients acquire the disease before the age of 20 years. This disease has a high stigmatizing impact but no ideal, aetiology-oriented, effective therapy has been found to date. Tacalcitol and other vitamin D analogues have been shown to have stimulating activity both on immunomodulatory mediators and on melanocytes in lesional skin.\n To investigate the efficacy and safety of tacalcitol ointment plus sunlight exposure in the treatment of nonsegmental vitiligo.\n A single-centre, randomized, double-blind, vehicle-controlled study including 80 patients with nonsegmental vitiligo was carried out in a specialized outpatient dermatology clinic within a tertiary care, university-affiliated hospital in Spain. Efficacy was assessed by quantification of the lesional repigmentation area at the end of the study compared with the baseline. Tacalcitol (n = 40) or matching placebo ointment (n = 40) was applied once a day at night. Daily exposure to sunlight for 30 min was performed. Treatment was continued for 4 months. The response of the lesions was clinically verified every 2 weeks by a blinded medical investigator. All adverse effects were recorded.\n Eighty adult patients with nonsegmental vitiligo were recruited. Over 16 weeks, 64 patients completed the study requirements. There was no significant difference in the repigmentation response at the 16-week time point between the vehicle + sunlight exposure and the tacalcitol + sunlight exposure groups. No reduction in the size of the lesions > 25% was observed in the tacalcitol-treated patients. No serious adverse effects were observed.\n The combination of tacalcitol with heliotherapy has no additional advantages compared with heliotherapy alone.", "To investigate the efficacy of epidermal noncultured cellular grafting in patients with vitiligo and the role of postinflammatory, spontaneous, or UV-induced pigmentation in obtaining repigmentation.\n A prospective, randomized, double-blind, placebo-controlled study.\n Ambulatory patients in an institutional practice. Patients were followed up for 3 to 12 months.\n A total of 33 paired, symmetrically distributed leukodermic lesions, all resistant to therapy, were observed in 28 patients. Nineteen patients appeared to have a stable vitiligo (group 1), whereas there was doubt about the stability of the disease in 9 patients (group 2).\n After laser ablation, a hyaluronic acid-enriched cellular graft was applied to 1 lesion while the paired lesion received placebo. Three weeks later all lesions were exposed to UV irradiation twice per week for approximately 2 months.\n Primarily, the percentage of repigmentation was assessed after 3, 6, and 12 months using a digital image analysis system. The repigmentation pattern was also evaluated after 1 and 3 months.\n A strongly significant difference between cellular grafts and placebo was observed after 3, 6, and 12 months (P<.001, P = .002, and P = .002, respectively). In group 1, repigmentation of at least 70% of the treated area was achieved in 55%, 57%, and 77% of the actively treated lesions 3, 6, and 12 months after treatment, whereas in group 2 repigmentation of at least 70% of the treated area was not observed at any time point. The repigmentation pattern was diffuse in 94% of the responding patients.\n After a strict preoperative selection for disease stability, transplantation resulted in repigmentation of at least 70% of the treated area in most actively treated vitiligo lesions. Repigmentation was primarily caused by the transplanted melanocytes.", "Narrow band UVB is succeeding psoralen and UVA irradiation as the main treatment of vitiligo vulgaris in several European countries. Vitamin B12 and folic acid deficiency in some vitiligo patients has prompted researchers to investigate the efficacy of these vitamins in the treatment of vitiligo. In the present controlled study we investigated the value of narrow band UVB phototherapy in the treatment of vitiligo and the possible additive effect of vitamin B12 and folic acid. Twenty-seven patients with long-term stable vitiligo were included and randomized in a \"UVB only\" (UVB) or \"UVB combined with vitamin B12 and folic acid\" (UVB+) group. Patients were irradiated thrice weekly for one year, whilst repigmentation was carefully monitored. In 92% (25/27) of the patients up to 100% repigmentation was seen. Repigmentation was notable in lesions on the face, neck and throat, lower arm, chest, back and lower legs, whilst repigmentation on the hands, wrists, feet and ankles proved to be minimal. Maximum repigmentation rates did not differ significantly between the UVB group and the UVB+ group. Our study reconfirms that narrow band UVB phototherapy is an effective treatment for vitiligo and shows that co-treatment with vitamin B12 and folic acid does not improve the outcome of treatment of vitiligo with narrow band UVB phototherapy.", "Vitiligo is a common pigmentary disorder with great cosmetic and psychological morbidity. No treatment available is a definitive cure. Systemic psoralen and ultraviolet A (PUVA) has been the mainstay of treatment. Narrow-band ultraviolet B (NB-UVB) has been recently introduced. Although retrospective comparative study of systemic PUVA and NB-UVB has been published from our centre, no prospective study has been reported to date.\n To investigate the position of NB-UVB vis-à-vis PUVA in terms of efficacy, time to repigment and adverse effects and to help decide if one therapy has an advantage over another in the treatment of vitiligo.\n It was a randomized, open, prospective study of 50 patients divided equally in TMP PUVA and NB-UVB groups. The study period was from January 2004 to June 2005.\n The mean degree of repigmentation attained in the NB-UVB group was 52.24% over a mean treatment period of 6.3 months, whereas in the PUVA group it was 44.7% in a mean period of 5.6 months (P=0.144). After excluding the results of therapy-resistant sites, that is, hands and feet, the mean degree of repigmentation in the NB-UVB group was 67.57%, whereas in the PUVA group it was 54.2% (P=0.007).\n NB-UVB performed better in comparison to TMP PUVA in terms of mean total repigmentation when traditionally considered therapy-resistant sites were excluded.", "Punch grafting followed by PUVA is an established therapy for stable vitiligo, but punch grafting followed by topical corticosteroid has never been evaluated.\n The aim of this study was to evaluate the efficacy of topical corticosteroid in perigraft pigmentation and to compare it with perigraft pigmentation after PUVA in patients with stable vitiligo.\n Fifty patients with stable vitiligo of various clinical types were subjected to punch grafting. In a randomized case study, these patients were divided into two groups: One group received post punch-grafting PUVA (group I) and the other group post punch-grafting topical application of fluocinolone acetonide 0.1% (group II). During the follow-up period of 6 months, six patients were lost to follow-up, and two patients were excluded from the study; 42 patients were evaluated for pigment spread and side effects.\n In group I, the average pigment spread was 6.38 mm, whereas in group II, it was 6.94 mm, showing a slightly higher pigment spread in group II, which was statistically not significant (P=0.301). There was no difference in response to therapy in patients having segmental vitiligo as compared with nonsegmental vitiligo. Cobblestoning, depigmentation of the grafts, infection, and graft displacement were the important side effects seen in some patients in both the groups.\n The study shows that the pigment spread with topical corticosteroid is comparable to that with PUVA. However, the studies with long-term follow-up are required to establish this. The advantages of topical corticosteroid are that its use is easy, less cumbersome, cheaper, and more cost effective than PUVA.", "Surgical therapy of vitiligo is indicated when depigmented macules are localized in areas that are known to respond poorly.\n The objective was to compare the results of treatment of vitiliginous macules localized in the dorsum of the hands and lower limbs by transplantation of cultured autologous melanocytes plus PUVA therapy (CMP), suction blister transplantation plus PUVA therapy (SBP), cryotherapy plus PUVA therapy (CP), and only PUVA therapy (OP).\n Twenty patients qualified for the study. The patients were split into two groups of 10 patients. In the first group, the CMP procedure was performed on one limb and OP on the other. In the second group, SBP and CP were used, respectively.\n The CMP procedure was successfully performed on only 6 of 10 patients, whereas SBP was carried out on all 10 patients. No significant difference was found between the number of successful transplants in both groups of patients. A total lack of effectiveness was found in CP and OP methods.\n This study demonstrated the advantage of the suction blister transplantation method over the autologous cultured melanocytes transplantation method because of the difficulties in cell culture establishment in some cases.", "In this paper, we report on 366 East Indian patients with vitiligo who were treated for 2 to 3 years with either 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP), or psoralen and sunlight. These patients with amelanotic macules had 10 to 70% skin involvement of 1 to 50 years duration. Male and female patients from ages 12 to 70 years were randomly assigned to 8 treatment groups; the study was conducted on a double-blind protocol. Patients in prone and supine positions were exposed to the sun for 45-60 minutes in gradually increasing doses between 11 a.m. and 2 p.m. thrice weekly and 2 hours after oral ingestion of the drug. The various drug dosage schedules investigated included 9 groups: 0.3 and 0.6 mg 8-MOP/kg; 0.8, 1.8, and 3.6 mg TMP/kg; a combination of 0.3 mg 8-MOP and 0.6 mg TMP/kg; 0.6 and 1.2 mg psoralen/kg, and a placebo. For ethical reasons, the placebo group was terminated after 9 to 12 months of therapy. All patients were photographed before enrollment and at intervals of 6, 12, 18, and 26 months during therapy. Of these patients treated for nearly 2 years, the faces of those 45% receiving the combination dose of 8-MOP plus TMP or low-dose 8-MOP (0.3 mg/kg) were fully repigmented, and nearly 60% achieved 75 to 100% repigmentation of the head and neck. The chest, abdomen, and back were repigmented nearly as well and better than the arms and legs. The patients receiving high-dose schedules of TMP and psoralen achieved better repigmentation response than those on lower dosage but still not as good as patients on 8-MOP or the combination group of 8-MOP plus TMP.(ABSTRACT TRUNCATED AT 250 WORDS)", "The first choice treatment for vitiligo vulgaris is narrow-band UVB (NB-UVB), but no satisfactory treatment exists.\n To investigate if Polypodium leucotomos, an antioxidative and immunomodulatory plant extract, improves NB-UVB-induced repigmentation.\n Fifty patients with vitiligo vulgaris randomly received 250 mg oral P. leucotomos or placebo three times daily, combined with NB-UVB twice weekly for 25-26 weeks.\n Repigmentation was higher in the P. leucotomos group vs. placebo in the head and neck area (44% vs. 27%, P = 0.06). Small repigmentation increases (P = n.s.) were observed for the trunk (6% increased repigmentation), extremities (4%), and hands and feet (5%) in the P. leucotomos group vs. placebo. Patients attending more than 80% of required NB-UVB sessions showed increased repigmentation in the head and neck area in the P. leucotomos group vs. placebo (50% vs. 19%, P < 0.002); no significant differences were seen in the other body areas. Patients with skin types 2 and 3 showed more repigmentation in the head and neck area in the P. leucotomos group vs. placebo (47% vs. 21%, P = 0.01), and no significant differences were seen in the other body areas. No conclusions could be drawn on skin types 4 and 5 due to low patient numbers.\n There is a clear trend towards an increase in repigmentation of vitiligo vulgaris affecting the head and neck area when NB-UVB phototherapy is combined with oral P. leucotomos. This effect may be more pronounced in light skin types.", "To study and compare the efficacy of combined 308-nm monochromatic excimer light (MEL) therapy with tacalcitol vs. that of MEL 308-nm therapy alone in treatment of vitiligo.\n Thirty-eight patients with vitiligo were enrolled in a single-blind, within patient controlled clinical trial. Symmetrical or nearby lesions were randomly applied with either topical tacalcitol cream or vehicle. Each lesion was treated weekly with the 308-nm MEL, for a total of 12 sessions. Patients were examined at monthly intervals. The mean number of sessions and the cumulative dosage for initial repigmentation were calculated.\n Thirty-five patients were evaluated. Treatment with tacalcitol and MEL resulted in higher percentages for excellent repigmentation (25.7%) compared with vehicle and MEL (5.7%) (P<0.05). Percentages for total response were 71.4% and 60%, respectively (P>0.05). The mean+/-SEM cumulative dose and number of excimer light exposures for initial repigmentation were, respectively, 3.93+/-0.59 J/cm2 and 4.52+/-0.49 at the tacalcitol side, and, respectively, 4.99+/-0.68 J/cm2 and 5.3+/-0.52 at the vehicle side (P<0.05).\n Our results have shown that concurrent topical tacalcitol potentiates the efficacy of the 308-nm MEL in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total dosage.", "Vitiligo is an acquired depigmenting disease with uncertain aetiopathogenesis, possibly associated with oxidative stress. Narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used and effective treatment.\n To evaluate the clinical effectiveness of NB-UVB and the repairing of oxidative stress-induced damage, using oral supplementation with an antioxidant pool (AP).\n Patients (n = 35) with nonsegmental vitiligo were enrolled in a randomized, double-blind, placebo-controlled multicentre trial. The treatment group received, for 2 months before and for 6 months during the NB-UVB treatment, a balanced AP containing alpha-lipoic acid, vitamins C and E, and polyunsaturated fatty acids. The area and number of lesions, as well as some parameters of the oxidation-reduction (redox) status of the peripheral blood mononuclear cells (PBMCs) were estimated at the beginning, after 2 months, and at the end of the trial.\n In total, 28 patients completed the study. After 2 months of AP supplementation, the catalase activity and the production of reactive oxygen species (ROS) were 121% and 57% of the basal values (P < 0.05 and P < 0.02 vs. placebo, respectively). The AP increased the therapeutic success of NB-UVB, with 47% of the patients obtaining > 75% repigmentation vs. 18% in the placebo group (P < 0.05). An increase in catalase activity to 114% (P < 0.05 vs. placebo) and decrease in ROS level of up to 60% (P < 0.02 vs. placebo) of the basal value was observed in PBMCs. Finally, the AP intake maintained the membrane lipid ratio (saturated : unsaturated fatty acids 1.8 : 3.1; P < 0.05), counteracting phototherapy-induced saturation.\n Oral supplementation with AP containing alpha-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB, reducing vitiligo-associated oxidative stress.", "To assess the safety and efficacy of topical 0.1% tacrolimus vs 0.05% clobetasol propionate.\n Randomized double-blind trial.\n Department of Dermatology, Hospital Central Dr Ignacio Morones Prieto, San Luis Potosí, México.\n From 20 children with vitiligo, 2 symmetrical lesions of about the same size and evolution time were selected. They were devoid of any topical or systemic therapy for 2 months prior to inclusion. Interventions Treatment with topical tacrolimus and clobetasol for a 2-month period.\n The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit. The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program. Characteristics of pigment, time of response, symptoms, telangiectasias, and atrophy were evaluated every 2 weeks.\n Eighteen (90%) of the 20 patients experienced some repigmentation. The mean percentage of repigmentation was 49.3% for clobetasol and 41.3% for tacrolimus. Lesions in 3 patients using clobetasol presented atrophy, and 2 lesions incurred telangiectasias; tacrolimus caused a burning sensation in 2 lesions.\n Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids, and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.", "A large variety of therapeutic agents are being used for the treatment of vitiligo, but treatment remains a challenge. Recently, monochromatic phototherapies such as 311-nm narrowband ultraviolet B therapy and 308-nm xenon chloride excimer laser have been reported to be an effective and safe therapeutic option in children and adult patients with vitiligo. Single reports stipulate that the addition of topically applied calcipotriol to phototherapy increases its effectiveness.\n The purpose of the present pilot study was to determine if the addition of topical calcipotriol increases the efficacy of the 308-nm xenon chloride excimer in the treatment of vitiligo.\n Ten patients with vitiligo with essentially bilateral symmetrical lesions were enrolled in this prospective right/left comparative, single-blinded trial conducted over a 15-month period. All patients received 308-nm XeCl excimer laser therapy three times weekly. Calcipotriol ointment (Daivonex) was applied to lesions on one side of the body twice daily.\n After 24 treatments (8 weeks), nine patients were evaluated. Eight patients showed evidence of repigmentation on both body sides, with no significant difference between the body side treated with calcipotriol and excimer laser and the side treated with excimer laser alone. The mean repigmentation rate was 22.4% (1-37%).\n The addition of calcipotriol ointment to 308-nm xenon chloride excimer laser phototherapy does not significantly enhance its efficacy. Small additive effects must be investigated in a larger trial.", "Minipunch grafting (MPG) and split-skin grafting (SSG) are common outpatient procedures for the surgical treatment of chronic stable vitiligo. However, there is a paucity of literature comparing the two procedures by the same group of investigators.\n To compare the two techniques in patients with chronic stable localized vitiligo.\n Sixty-four patients with stable vitiligo of 6 months duration were randomized into two groups to be taken up for MPG or SSG in a representative patch followed by PUVAsol therapy for 3 months. They were evaluated 3 months postoperatively for the degree of repigmentation and side effects.\n In the MPG group, 644 grafts, 2.5 mm in size, were placed on a total vitiliginous area of 521.25 cm2, whereas in the SSG group, 153 grafts covered a 1,489 cm2 recipient area. Three months postoperatively, in the first group, 15 cases (44.1%) showed very good to excellent (> 75%) repigmentation compared with 25 cases (83.3%) in group 2. Following MPG, 81 grafts (12.57%) were rejected. Cobblestoning was the main side effect, occurring in 13 cases (38.23%), and a variegated appearance was observed in 7 (20.58%) patients. The complications noted after SSG were achromic fissuring in four (13.3%) cases, graft contracture in four grafts (2.61%) in three patients, and rejection of seven grafts (4.57%) in one case; tire-pattern appearance in two patients (6.6%); milia formation in four (13.3%) patients; and depigmentation of the grafts in two (6.6%) cases. In both groups, superficial scarring was noted at the donor site in all cases, whereas hypertrophic scarring occurred in 3 (10%) patients after SSG.\n SSG carries a distinct advantage over MPG in producing excellent cosmetic matching over larger areas using fewer grafts, especially over the face and extremities.", "To observe the clinical efficacy of Zengse Pill ( ZSP) on patients with vitiligo of qi-stagnancy and blood-stasis syndrome type (V-QB), and to preliminarily explore its mechanism of action.\n Sixty-five V-QB patients, with their diagnosis confirmed by clinical examination, were randomized by digital table method into two groups, with 31 patients in the control group and 34 in the treatment group. Cobamamide (2 tablets) was administered orally to all patients, and Psoralea tincture (a self-formulated preparation) was applied externally thrice a day. In addition, for patients in the treatment group, ZSP was given orally, at 5 pills per dose, 3 times every day. The therapeutic course for both groups was 3 months. Patients were re-examined every half-month, and changes in the skin lesions were observed and recorded. The levels of lymphocyte subsets, serum immune globulin, and complement C3 and C4 in patients were determined before and after the therapeutic course and compared with the corresponding indexes determined in 21 healthy subjects.\n The total effective rate in the treatment group was 82.4%, which was markedly higher than that in the control group (54.8%), showing a significant difference (P<0.05). After treatment, CD(4) (+) percentage, CD(4) (+)/CD(8) (+) ratio, and blood levels of C3 and C4 increased, while CD(8) (+) percentage decreased in the treatment group (P<0.05 or P<0.01). All these indexes remained unchanged in the control group, and the respective comparisons between groups showed significant differences (P<0.01).\n ZSP has a definite clinical effect on the treatment of V-QB but with no evident adverse reactions, and it can increase the CD(4) (+) percentage, CD(4) (+)/CD(8) (+) ratio, and the levels of serum C3 and C4, thus regulating the immunity of the organism, which might be one of its mechanisms of action.", "nan", "Vitiligo is a common, idiopathic, acquired, depigmenting disease characterized by loss of normal melanin pigments in the skin. The most interesting treatment methods for extensive vitiligo involve psoralen plus ultraviolet A (PUVA) therapy and ultraviolet (UV)-B phototherapy, particularly narrow-band UV-B. In this randomized and comparative study, we investigated the safety and efficacy of narrow band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of generalized vitiligo. Of the 40 vitiligo patients enrolled in the study, 15 were treated with the calcipotriol plus narrow-band UV-B (NBUVB) and 25 with narrow band UV-B alone. The patients were randomized into two NBUVB treatment groups. The first group, consisting of 24 patients (all male), received only NBUVB treatment; the second group, consisting of 13 patients (all male) applied 0.05% topical calcipotriol ointments twice daily. Both groups were irradiated with NBUVB (311 nm). In the NBUVB group, the percentage of the body surface affected was reduced from 27.21 +/- 10.41% to 16.25 +/- 8.54% after a mean of 30 treatment sessions. The mean repigmentation percentage was 41.6 +/- 19.4%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 19 patients (19/24; 79.17%) had clinically good results. In the NBUVB plus calcipotriol group, the percentage of the body surface affected was reduced from 23.35 +/- 6.5% to 13.23 +/- 7.05% after a mean of 30 treatment sessions. The mean repigmentation percentage was 45.01 +/- 19.15%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 10 patients (10/13; 76.92%) had clinically good results. Statistically significant intragroup reductions from the baseline percentage of the body surface affected were seen at the endpoint of treatment for the two treatment groups (P < 0.001). However, there was no statistically significant difference between the two treatment groups at the end of therapy with respect to the reduction of repigmentation rates (P > 0.05). The present study reconfirmed the efficacy of NBUVB phototherapy in vitiligo. It can be a therapeutic option considered in the management of patients with vitiligo. However, addition of topical calcipotriol to NBUVB did not show any advantage.", "nan", "nan", "A large variety of therapeutic agents are being tried for the treatment of vitiligo, but psoralens continue to be mainstay of treatment although they are not uniformly effective. Recent advances in pathophysiology have established a perturbed calcium homeostasis in affected skin, and melanocytes were shown to express vitamin D3 receptors.\n The purpose of present study was to determine the efficacy of the combination of PUVAsol with topical calcipotriol in the treatment of vitiligo.\n Nineteen patients with essentially bilateral symmetrical lesions were enrolled in a randomized, double-blind, right/left comparative study of 18 months duration. An oral dose of 0.6 mg/kg 8-methoxypsoralen was given 2 h before exposure to sunlight thrice weekly to all patients. The patients were advised to apply calcipotriol (50 microgram/g) on one side of the body and placebo ointment over the lesions on the other side twice daily.\n At the end of 6 months, 12 patients (70%) showed marked to complete improvement on calcipotriol-treated sides as compared to 6 patients (35%) showing similar improvement on placebo-treated sides (p <0.05). At the end of treatment, 13 patients (76%) showed marked improvement in calcipotriol-treated lesions whereas 9 patients (53%) showed moderate to marked improvement in placebo-treated lesions. The repigmentation of hands and feet was much better with the combination of PUVAsol and calcipotriol.\n The combination of PUVA and calcipotriol is highly effective and works faster and may be used for shortening the therapy with PUVA in the treatment of vitiligo.", "NB-UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year. Skin ablation with mechanical dermabrasion with 5Fluorouracil (5FU) was introduced to treat vitiligo in 1983. This was modified replacing the mechanical dermabrasion by erbium-YAG (ER:YAG) laser ablation and resulted in better prognosis in periungual vitiligo. Purpose: In the present study, we are exploring the effect of the use of ER:YAG laser skin ablation and application of 5FU on the outcome of short-term NB-UVB therapy for patients with non-segmental vitiligo (NSV).\n This study included 50 adult patients with a total of 65-paired symmetrical NSV lesions in different body parts. One side was treated with ER:YAG laser ablation, followed by 5FU application before simultaneous NB-UVB therapy of both sides for a maximum period of 4 months. The outcome was then evaluated both qualitatively and quantitatively.\n The overall response to therapy was better using the combination therapy. Fifty patients (78.1%) experienced a moderate-marked repigmentation response in the combination group compared with 23.4% in the mono-therapy group. The response was significantly higher when using the combination therapy in different body parts (P value is <0.05), except for feet lesions, which were better but not statistically significant (P value=0.15). Tolerable pain during ablation or at sites of 5FU application was reported in all cases. Transient hyperpigmentation occurred in 30% of cases and 3.1% of lesions healed by a transient slate blue color. Half of the treated periungual lesions showed a temporary tiny brownish spot on nail plates and Köebnerization was not detected in any patient.\n We concluded that prior use of ER:YAG laser skin ablation, followed by 5FU application before NB-UVB phototherapy for vitiligo is a safe and tolerable technique that improves the outcome of short-term NB-UVB therapy and is expected to increase patient compliance.", "To compare the efficacy and safety of using a combination of fluticasone propionate (FP) and UV-A with that of either drug used alone in the long-term treatment of vitiligo.\n Prospective, randomized, controlled, left-right comparison study. Repigmentation was judged by a single dermatologist (L.N.-K.) and skin thickness was scored by a pathologist (using biopsy samples), a dermatologist (L.N.-K.) (visually), and patients (using a standard questionnaire).\n Netherlands Institute for Pigmentary Disorders, Amsterdam.\n Patients with lesions on arms, legs, and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A (FP group) or with UV-A alone and a combination of FP and UV-A (UV-A group). Fluticasone propionate cream was applied once daily at about bedtime, and UV-A (10 J/cm2) exposure was twice a week. Patients attended the clinic at 3-month intervals.\n One hundred thirty-five patients were included, 96 of whom were evaluable after 9 months. Patients not reaching the end point withdrew because of insufficient repigmentation (n = 23), decreased motivation (n = 11), or protocol violations (n = 5). No patient (irrespective of whether they withdrew) experienced any adverse effects. The FP and UV-A groups were comparable with respect to sex, age, and location of lesions. On average, combination treatment was 3 times more effective than either UV-A or FP treatment alone. In the FP group, no atrophy was seen after 9 months with either treatment. In the UV-A group, a little atrophy was detected twice: as well during UV-A treatment alone as during combination treatment.\n Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone, but large inter-individual differences occur. Fluticasone propionate, UV-A, and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo.", "Previous reports have shown the effectiveness of a basal layer cell suspension in the treatment of stable vitiligo; however, there has been no mention in the literature until now of the optimal number of melanocytes required in an autologous noncultured epidermal suspension for transplantation to obtain early and acceptable results.\n In this randomized prospective study, we compared the efficacy of two different dilutions to determine the optimum density of melanocytes required for transplantation to achieve early and cosmetically acceptable results. We enrolled 20 patients with stable vitiligo with a body surface area involvement of< 10%.\n Fifty per cent of patients in Group A (where the recipient area transplanted was approximately three times the size of the donor area, and the density of melanocytes transplanted per square millimeter was approximately 231.60+/- 27.03) showed marked (> 75%), 20% moderate, 10% mild, and 20% minimal repigmentation (or no response). In Group B (where the recipient area was increased to five-fold the donor area), none of the patients showed marked, 10% showed moderate, 20% showed mild, and 70% showed either minimal or no repigmentation. The density of melanocytes transplanted in this group was 154.90+/- 27.65/mm(2). The extent of repigmentation was significantly greater (P< 0.05) in Group A than in Group B, and the density of melanocytes in the suspension was also significantly greater (P< 0.01) in Group A than in Group B.\n We contend that the minimum number of melanocytes required to produce satisfactory repigmentation is probably in the range of 210-250/mm(2).", "Vitiligo is an acquired, pigmentary skin disorder which is disfiguring and difficult to treat. In an earlier open label study in adult patients with vitiligo, pimecrolimus cream 1% was reported to have similar efficacy as clobetasol propionate 0.05%. We performed a double-blind, intrapatient comparison of pimecrolimus cream 1% with placebo cream.\n Twenty adult Caucasians with symmetrical vitiligo (predominantly on extremities, none in the face) were treated b.i.d. for 6 months left/right with pimecrolimus/vehicle (N = 10) or vehicle/pimecrolimus (N = 10), respectively. Primary efficacy endpoint was the size of the target lesion at month 6 and secondary efficacy endpoint was re-pigmentation.\n Treatment with pimecrolimus cream 1% or vehicle resulted in no significant change in mean target lesion size. Modest repigmentation (1-25%) was noted with pimecrolimus at month 2 in 12 of 17 patients (vehicle: 9 of 17 patients). Afterwards, the number of patients who experienced an improvement of pigmentation steadily decreased (3 of 14 patients with pimecrolimus and 2 of 14 with placebo at month 6). Treatment was well tolerated. There were no treatment-related adverse events, no induction of skin atrophy nor any other application site side effects.\n In this group of adult patients with symmetrical vitiligo, treatment of body lesions (except face) with pimecrolimus cream 1% could not be shown to be effective.", "Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo.\n We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo.\n Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(-1) cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated.\n Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/- 13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/- 0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on the placebo side, respectively (P < 0.001). For complete repigmentation, respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively).\n Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.", "Recently the beneficial effect of excimer laser treatment has been reported for patients with vitiligo. The influence of treatment frequency on this effect is not clear.\n To determine the optimal frequency of 308-nm excimer laser therapy for vitiligo.\n In this prospective, university-based hospital study over 12 weeks we enrolled 14 patients. Each had at least three stable vitiligo lesions in the same body area. The three stable vitiligo lesions in each subject were randomly assigned to receive excimer laser treatment once (1 x), twice (2 x) and three times (3 x) weekly, respectively. The initial ultraviolet (UV) dose was 50 mJ cm(-2) less than the 308-nm minimal erythematous dose in vitiligo skin. The UV dose was increased at each treatment session according to the erythematous response to the previous treatment.\n Thirteen subjects were treated for at least 6 weeks; seven were treated for all 12 weeks. At 6 weeks, the repigmentation rates for treated lesions were 8% (1/13) after 1 x weekly treatment, 23% (3/13) after 2 x weekly treatment and 62% (8/13) after 3 x weekly treatment (P = 0.0134; 3 x vs. 1 x weekly); at 12 weeks, these rates were 46% (6/13), 62% (8/13) and 69% (9/13), respectively (P = NS; 3 x vs. 1 x weekly). Repigmentation initiation correlated with treatment number, regardless of frequency (P = NS). As shown by Kaplan-Meier analysis, repigmentation occurred earliest in the most frequently treated lesions (P = 0.0336). At 12 weeks, the projected repigmentation rates for 1 x, 2 x and 3 x weekly treatment approached each other (60%, 79% and 82%, respectively); the mean repigmentation grades (on a scale of 0-5) for 1 x, 2 x and 3 x weekly treatment were 1.7, 2.4 and 3.3, respectively (P = 0.018; 3 x vs. 1 x weekly). Laser-induced repigmentation persisted in most cases over the entire follow-up of 12 months after the end of treatment.\n 308-nm excimer laser therapy is effective against vitiligo. Although repigmentation occurs fastest with 3 x weekly treatment, the ultimate repigmentation initiation seems to depend entirely on the total number of treatments, not their frequency. However, treatment periods of more than 12 weeks may be necessary to obtain a satisfactory clinical repigmentation, particularly when vitiligo lesions are treated only 1 x or 2 x compared with 3 x weekly.", "Vitiligo is a pigmentary disorder which may have disfiguring consequences. Its treatment remains a challenge.\n We designed a parallel-group randomized controlled trial to compare the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in patients with vitiligo unresponsive to previous treatment with topical steroids or narrow-band ultraviolet (UV) B phototherapy.\n Consecutive patients aged 18-75 years with nonsegmental vitiligo localized on the face and/or neck lacking response to previous conventional treatment were eligible. In total, 84 patients (44 women and 40 men, mean age 44 years) were randomized to 308-nm excimer laser phototherapy twice weekly alone or in combination with topical hydrocortisone 17-butyrate cream twice daily for three periods of 3 weeks followed by a 1-week steroid-free interval. The primary outcome was a reduction of at least 75% of the overall lesional areas as judged by automatic image analysis on reflected UV photographs, conducted blind to treatment assignment, at 12 weeks compared with baseline. Secondary outcomes were clearance, and improvements on Physician's Global Assessment (PGA) and Skindex-29 scores.\n A total of 76 (90%) patients completed the study. In an intention-to-treat analysis, seven [16.6%; 95% confidence interval (CI) 5.3-27.8%] patients in the excimer monotherapy arm and 18 (42.8%; 95% CI 27.8-57.8%) in the combination arm showed > or = 75% reduction of vitiligo lesions at 12 weeks (chi(2) test 6.89, P = 0.0087). Clearance was observed in two (4.7%; 95% CI 1.6-11.2%) and nine (21.4%; 95% CI 9.0-33.8%) patients, respectively (Fisher's exact test P = 0.04). A significant difference also emerged for PGA scores, while no difference was documented for Skindex-29.\n Recalcitrant vitiligo of the face and neck may benefit from the combination of excimer laser phototherapy with topical hydrocortisone 17-butyrate cream.", "nan", "Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease.\n To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder.\n Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board-approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results.\n Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy.\n Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.", "There is currently no quantitative tool for evaluating vitiligo treatment response using parametric methods.\n To develop and apply a simple clinical tool, the Vitiligo Area Scoring Index (VASI), to model the response of vitiligo to narrowband UV-B (NB-UV-B) phototherapy using parametric tests.\n Prospective, randomized, controlled, bilateral left-right comparison trial.\n North American tertiary care, university-affiliated phototherapy center.\n Patients older than 18 years with stable vitiligo involving at least 5% of their total body surface in a symmetric distribution.\n Treatment with NB-UV-B was given 3 times a week to half of the body on all patients for either 60 treatments or 6 months. The contralateral side served as a no-treatment control.\n Repigmentation was assessed using the VASI, which was based on a composite estimate of the overall area of vitiligo patches at baseline and the degree of macular repigmentation within these patches over time. The VASI was validated separately against physician and patient global assessments. The overall reductions in VASI for NB-UV-B and control groups were modeled by multilevel regression with random effects and compared parametrically.\n The VASI scoring correlated well with both patient and physician global assessments (P =.05 and P<.001, respectively, using ordinal logistic regression). The extent of repigmentation after 6 months on the treated side was 42.9% (95% confidence interval, 26.7%-59.0%) vs 3.3% (95% confidence interval -19.3% to 30.0%) on the untreated side (P<.001). A significant difference between control and NB-UV-B groups was apparent within the first 2 months of therapy. The legs, trunk, and arms were much more likely to repigment than the feet and hands.\n The VASI is a quantitative clinical tool that can be used to evaluate vitiligo parametrically. Patients treated with NB-UV-B can be expected to achieve approximately 42.9% repigmentation of their vitiligo after 6 months of treatment, with the greatest response being achieved over the trunk and nonacral portions of the extremities.", "Recently, narrow-band ultraviolet B (NB-UVB) and topical immunomodulators have been successfully used in the treatment of vitiligo.\n To determine whether the combination of pimecrolimus with NB-UVB accelerates the response time and/or improves the degree of response in patients with vitiligo.\n Sixty-eight patients with vitiligo enrolled in this randomized, double-blind, placebo-controlled study. The patients were randomized into two groups and treated with NB-UVB plus either pimecrolimus or placebo for 3 months. Tri-weekly radiation was started at 280 mJ/cm(2), with 15% increments for each subsequent treatment until erythema was reported or a maximum of 800 mJ/cm was achieved. At baseline and 6 and 12 weeks after commencement of therapy, vitiliginous patches were measured.\n Fifty patients completed the 3-month study. No significant side effects except self-limited erythema and pruritus were observed. After 12 weeks of treatment, repigmentation of the facial lesions was higher in patients treated with combined pimecrolimus and NB-UVB compared with the placebo plus NB-UVB group (64.3 vs 25.1%) (p < 0.05%). There was no statistically significant difference in the repigmentation rate between the two groups on other body areas.\n On the face, NB-UVB works better if combined with pimecrolimus 1% cream rather than used alone.", "Treatment of vitiligo is a challenge. Steroids are known to be effective but are associated with serious adverse effects. Many uncontrolled studies have shown calcipotriol to be a promising therapeutic modality in vitiligo.\n To conduct a randomized trial to evaluate the effect of topical calcipotriol ointment (0.005%) and betamethasone dipropionate (0.05%) cream, given alone or in combination, in treatment of localized vitiligo.\n Forty-nine patients with vitiligo affecting 5% of their skin were recruited. Patients were randomized into three groups. Group I patients were treated with betamethasone dipropionate (0.05%) cream twice daily. Group II patients were treated with calcipotriol ointment (0.005%) twice daily, and group III with betamethasone dipropionate (0.05%) in the morning and calcipotriol (0.005%) in the evening.\n Forty-five patients completed the study period of 3 months with 15 patients in each group. No patient achieved excellent (> 75%) pigmentation. Marked (50% to 75%) repigmentation was observed in 2 (13.3%), 1 (6.7%) and 4 (26.7%) patients in groups I, II and III, respectively. Moderate (25-50%) repigmentation was observed in 7 (46.7%), 5 (33.3%) and 7 (46.7%) patients in groups I, II and III, respectively. Patients with < 25% pigmentation were termed as minimal pigmentation or no response. The mean time for initial pigmentation to appear was 9.04 +/- 2.0 weeks in group I, 10.18 +/- 1.6 weeks in group II and 5.17 +/- 2.4 weeks in group III (P < 0.01). The acquired pigmentation in the lesions was more stable in group III as compared with patients in groups II and I (P < 0.01). Side-effects in the form of atrophy and lesional burning sensations were more common in group I when compared with groups II and III (P < 0.05).\n Combined therapy appeared to give a significantly faster onset of repigmentation along with better stability of the achieved pigmentation and with lesser number of side-effects.", "Immunosuppressive agents are used widely in the treatment of vitiligo. Corticosteroids are used either alone or as adjuvant therapy by many practitioners. Cyclophosphamide and cycloporine-A have also been used with variable success. Azathioprine may have the potential for the treatment of vitiligo alone or in combination with other modalities.\n To compare the efficacy of combined low-dose azathioprine and oral PUVA therapy versus oral PUVA therapy alone for the treatment of vitiligo.\n A total of 60 vitiligo patients were randomized to receive either azathioprine (0.6-0.75 mg/kg) and oral PUVA therapy (group 1) or oral PUVA therapy alone (group 2). Patients were followed for 4 months. A graph transparency with squares of 2.5 x 2.5 mm was used to measure the rate of repigmentation after 4 months of therapy.\n Perifollicular repigmentation started after a mean of five sessions in group 1, and eight sessions in group 2. The mean total repigmentation rate after 4 months was 58.4% for group 1 and 24.8% for group 2. No serious side effects were seen during or after treatment.\n Azathioprine may potentiate the repigmentary effects of PUVA therapy in vitiligo patients. A limitation of the study is the lack of validated measures for vitiligo assessment.", "Several modalities of treatment have been tried in vitiligo with varied results; however, Indian data on comparative studies of two or more therapies are limited.\n We compared different phototherapy methods with an oral steroid as an adjunct to determine the method with the best tolerability and efficacy.\n Eighty-six patients with progressive vitiligo were randomly assigned to different study groups according to a continuous selection method over a period of one year. Group 1 was given OMP + PUVA, group 2 OMP + UVB (NB), group 3 OMP + UVB (BB) and group 4 was given OMP alone. Each patient was followed up for six months and then released from treatment. Clinical evaluation was made at the end of three and six months.\n In group 1 (OMP + PUVA), marked improvement was seen in 18.51% while moderate improvement was seen in 66.66% of the patients. Marked improvement was seen in 37.03% in group 2 (OMP + NB-UVB) while 44.44% had moderate improvement. In group 3 (OMP + BB UVB), 8.33% showed marked improvement while moderate improvement was seen in 25% of the patients. Marked and moderate improvement was seen in 5 and 10% of group 4 (OMP) patients, respectively.\n Our study compared four treatment modalities in vitiligo patients, out of which oral minipulse of steroids (OMP) only had an adjunct value and was not very effective by itself. Narrow band UVB has a definite edge over broad band UVB and should be preferred when both options are available. NB-UVB and PUVA showed comparable efficacy.", "Vitiligo is an acquired pigmentary disorder characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Recently, it has been shown that narrowband ultraviolet B (NB-UVB) phototherapy may be more effective than psoralen and ultraviolet A (PUVA) photochemotherapy in treating vitiligo, and that 308-nm monochromatic excimer light (MEL) may present some advantages as compared to NB-UVB for the treatment of vitiligo. AIM The aim of this study was to compare the effectiveness of NB-UVB phototherapy and 308-nm MEL in vitiligo patients.\n The study was done in a randomized, investigator-blinded and half-side comparison design. Twenty-one subjects with symmetrical vitiligo lesions were enrolled in this study. Vitiligo lesions on one body side were treated twice weekly for 6 months with 308-nm MEL, while NB-UVB phototherapy was used to treat lesions on the opposite side.\n At the end of the study six lesions (37.5%) treated with 308-nm MEL and only one lesion (6%) treated with NB-UVB achieved an excellent repigmentation (score 4) while four lesions (25%) treated with 308-nm MEL and five lesions (31%) treated with NB-UVB showed a good repigmentation (score 3).\n It appears that 308-nm MEL is more effective than NB-UVB in treating vitiligo lesions and it induces repigmentation more rapidly.", "Narrowband ultraviolet B (NB-UVB) phototherapy, with a 308-nm xenon chloride excimer laser, and targeted UVB phototherapy have produced encouraging therapeutic results for vitiligo. However, very few studies employing broadband UVB exist. Moreover, there has been no direct comparison study between broadband UVB and NB-UVB for the treatment of vitiligo. The aims of this study were to compare the repigmenting efficacy of targeted broadband UVB phototherapy with that of NB-UVB in an equi-erythemogenic manner. Twenty identical vitiliginous lesions from 10 patients were randomly allocated to receive either targeted broadband UVB or targeted NB-UVB phototherapy. UV fluences were started at 50% of the minimal erythema dose detected within the vitiliginous patches, then increased gradually, in the same manner, to ensure equi-erythemogenic comparison. Treatments were carried out twice weekly for 12 weeks. The results show that grade 1, i.e. 1-25% repigmentation, to grade 2, 26-50% repigmentation, occurred in 6 of 10 subjects. Responses in terms of repigmentation, de-pigmentation, or lack thereof, were similar between lesions receiving broadband and NB-UVB phototherapy. Onset of repigmentation occurred as early as 4 weeks of treatment in most subjects. Treatments were well tolerated, with only minimal erythema and hyperpigmentation.\n The study was carried out in a small number of patients with skin types III, IV and V. The irradiation device was a targeted UVB device and thus the results may not be applicable to other light sources, such as the excimer laser or total-body irradiation cabinets. In conclusion, targeted broadband UVB produces similar clinical responses to targeted NB-UVB in the treatment of the non-segmental type of vitiligo.", "nan", "To compare the efficacy of combined tacrolimus and 308-nm excimer laser therapy vs 308-nm excimer laser monotherapy in treating vitiligo.\n Comparative, prospective, randomized, intraindividual study.\n Fourteen patients, aged 12 to 63 years, with Fitzpatrick skin types II to IV.\n For each patient, 4 to 10 target lesions were chosen. The treatment applied to each target lesion was randomized by drawing lots. Each lesion was treated twice a week by the 308-nm excimer laser, for a total of 24 sessions. Initial fluences were 12 mcal/cm(2) (50 mJ/cm(2)) less than the minimal erythemal dose in vitiliginous skin. Then, fluences were increased by 12 mcal/cm(2) every second session. Moreover, topical 0.1% tacrolimus ointment was applied twice daily on target lesions receiving the combined tacrolimus and excimer laser treatment (group A). Group B target lesions received only excimer laser monotherapy. For each treated lesion, the untreated lesion on the opposite side served as the control. Tolerance was evaluated by a visual analog scale, and secondary events were recorded at each session.\n Treatment efficacy, which was blindly evaluated by 2 independent physicians by direct and polarized light photographs taken before and after treatment.\n Forty-three lesions were treated (23 in group A and 20 in group B). All patients completed the study. Repigmentation was observed in all group A lesions (100%) and in 17 (85%) of the 20 group B lesions. Repigmentation was not observed in the untreated lesions (control group). A repigmentation rate of 75% or more was obtained in 16 (70%) of the 23 group A lesions and in 4 (20%) of the 20 group B lesions. In UV-sensitive areas (the face, neck, trunk, and limbs, with the exception of bony prominences and extremities), 10 (77%) of 13 group A lesions had a repigmentation rate of 75% or more vs 4 (57%) of 7 group B lesions. In classically UV-resistant areas, 6 (60%) of 10 group A lesions had a repigmentation rate of 75% or more vs 0 of the 13 group B lesions. The mean number of sessions necessary for an improvement of repigmentation was 10 in group A and 12 in group B. Adverse effects have been limited, and tolerance was excellent.\n The combination treatment of 0.1% tacrolimus ointment plus the 308-nm excimer laser is superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant vitiliginous lesions (P<.002). The efficacy and the good tolerance of the 308-nm excimer laser in monotherapy for treating localized vitiligo were also confirmed, but this treatment regimen should be proposed only for UV-sensitive areas.", "Surgical techniques have recently been introduced for patients with vitiligo. Randomized controlled trials have not been performed.\n To compare the efficacy and side-effects of two surgical methods (suction blister vs. thin split-thickness graft technique) for the treatment of vitiligo.\n Three suction blisters, approximately 0.8 cm in diameter, made with a special tool attached to a vacuum extractor, which were converted to erosions by removal of the roofs of the bullae, and one round erosion of approximately the same diameter, made using a silver knife, were created. One roof of a blister and two cutaneous thin split-thickness grafts taken from the gluteal region were transferred onto recipient vitiliginous areas; one was left alone. The results were evaluated by one non-blind and two blind observers bimonthly during the 3-month follow-up period.\n Repigmentation rates were 25-65% in the suction blister technique and 90% in the thin split-thickness graft technique (P < 0.001).\n The thin split-thickness graft technique is superior to the suction blister technique in treating vitiligo.", "Vitiligo is a skin disease characterized by loss of normal pigmentation in the skin. Several treatments exist but none is really effective. Recently, perturbations of calcium homeostasis in vitiliginous epidermis have been described.\n Based on these findings, the aim of this prospective, randomized, open-label study was to compare the effectiveness of narrow-band ultraviolet B (NB-UVB) phototherapy alone and the combination of NB-UVB and topical application of the vitamin D(3) analogue tacalcitol in the treatment of vitiligo.\n In total, 32 subjects with generalized vitiligo and symmetrical lesions were enrolled in the study. Subjects were instructed to apply tacalcitol ointment daily to the lesion on the side randomly selected to receive combination therapy. All subjects received NB-UVB phototherapy on a twice-weekly schedule.\n Addition of topical tacalcitol to NB-UVB treatment improved the extent of repigmentation and increased the response rate in patients with vitiligo compared with NB-UVB treatment alone.\n Application of tacalcitol ointment in combination with twice-weekly NB-UVB phototherapy is an effective alternative treatment for patients with generalized vitiligo." ]

[ "10965008", "8748595" ]

[ "Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy.", "Spinal cord stimulation versus reoperation for failed back surgery syndrome: a prospective, randomized study design." ]

[ "Chronic reflex sympathetic dystrophy (also called the complex regional pain syndrome) is a painful, disabling disorder for which there is no proven treatment. In observational studies, spinal cord stimulation has reduced the pain associated with the disorder.\n We performed a randomized trial involving patients who had had reflex sympathetic dystrophy for at least six months. Thirty-six patients were assigned to receive treatment with spinal cord stimulation plus physical therapy, and 18 were assigned to receive physical therapy alone. The spinal cord stimulator was implanted only if a test stimulation was successful. We assessed the intensity of pain (on a visual-analogue scale from 0 cm [no pain] to 10 cm [very severe pain]), the global perceived effect (on a scale from 1 [worst ever] to 7 [best ever]), functional status, and the health-related quality of life.\n The test stimulation of the spinal cord was successful in 24 patients; the other 12 patients did not receive implanted stimulators. In an intention-to-treat analysis, the group assigned to receive spinal cord stimulation plus physical therapy had a mean reduction of 2.4 cm in the intensity of pain at six months, as compared with an increase of 0.2 cm in the group assigned to receive physical therapy alone (P<0.001 for the comparison between the two groups). In addition, the proportion of patients with a score of 6 (\"much improved\") for the global perceived effect was much higher in the spinal cord stimulation group than in the control group (39 percent vs. 6 percent, P=0.01). There was no clinically important improvement in functional status. The health-related quality of life improved only in the 24 patients who actually underwent implantation of a spinal cord stimulator. Six of the 24 patients had complications that required additional procedures, including removal of the device in 1 patient.\n In carefully selected patients with chronic reflex sympathetic dystrophy, electrical stimulation of the spinal cord can reduce pain and improve the health-related quality of life.", "Retrospectively reported results of spinal cord stimulation compare favorably with those of neurosurgical treatment alternatives for the treatment of failed back surgery syndrome, including reoperation and ablative procedures. There has been no direct prospective comparison, however, between SCS and other techniques for pain management. Therefore, we have designed a prospective, randomized comparison of spinal cord stimulation and reoperation in patients with persistent radicular pain, with and without low back pain, after lumbosacral spine surgery. Patients selected for reoperation by standard criteria are randomly assigned to initial treatment by one or the other technique. The primary outcome measure is the frequency of crossover to the alternative procedure, if the results of the first have been unsatisfactory after 6 months. Results for the first 27 patients reaching the 6-month crossover point show a statistically significant (p = 0.018) advantage for spinal cord stimulation over reoperation. Many other potentially important outcome measures will now be followed long-term as a larger overall study population accumulates." ]

[ "2404633", "11454114", "1788664", "7915754", "11459433", "9413374", "16376202", "16828435", "16890883", "17210383", "12618567", "6060733", "16205431", "16858218", "4819838", "8872646", "1863010", "2647051", "11472042", "15890545", "12528763" ]

[ "Benefit of exercise conditioning for patients with peripheral arterial disease.", "Exercise rehabilitation improves functional outcomes and peripheral circulation in patients with intermittent claudication: a randomized controlled trial.", "[Effect of a 2-year ambulatory vascular sports program on walking distance in claudication patients--a controlled study].", "Treating peripheral arterial occlusive disease: pentoxifylline vs exercise.", "Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.", "Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response?", "Upper- vs lower-limb aerobic exercise rehabilitation in patients with symptomatic peripheral arterial disease: a randomized controlled trial.", "Short-term effects of cycle and treadmill training on exercise tolerance in peripheral arterial disease.", "The EXercise versus Angioplasty in Claudication Trial (EXACT): reasons for recruitment failure and the implications for research into and treatment of intermittent claudication.", "The effect of supervised exercise and cilostazol on coagulation and fibrinolysis in intermittent claudication: a randomized controlled trial.", "PoleStriding exercise and vitamin E for management of peripheral vascular disease.", "Effect of daily muscular exercise in patients with intermittent claudication.", "Experimental model of pain-free treadmill training in patients with claudication.", "Red blood cell deformability in patients with claudication after pain-free treadmill training.", "Metabolic activity of skeletal muscle in patients with peripheral arterial insufficiency.", "Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease.", "Physical training and antiplatelet treatment in stage II peripheral arterial occlusive disease: alone or combined?", "Intermittent claudication--surgical reconstruction or physical training? A prospective randomized trial of treatment efficiency.", "Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.", "Improvement of the walking ability in intermittent claudication due to superficial femoral artery occlusion with supervised exercise and pneumatic foot and calf compression: a randomised controlled trial.", "The effects of exercise training on walking function and perception of health status in elderly patients with peripheral arterial occlusive disease." ]

[ "Patients with atherosclerotic peripheral arterial disease (PAD) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the resultant pain of intermittent claudication. To evaluate the benefit of exercise training as a treatment for patients with PAD, as well as possible mechanisms associated with improvement, we randomly assigned 19 men with disabling claudication to treated and control groups. Treatment consisted of supervised treadmill walking (1 hr/day, 3 days/wk, for 12 weeks) with progressive increases in speed and grade as tolerated. Graded treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance. After 12 weeks, treated subjects had increased their peak walking time 123%, peak oxygen consumption 30%, and pain-free walking time 165% (all p less than 0.05). Control subjects had no change in peak oxygen consumption, but after 12 weeks, peak walking time increased 20% (p less than 0.05). In treated subjects, maximal calf blood flow (measured by a plethysmograph) increased 38 +/- 45% (p less than 0.05), but the change in flow was not correlated to the increase in peak walking time. Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle. In treated subjects, a 26% decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time (r = -0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the effects of a 6-month exercise program on ambulatory function, free-living daily physical activity, peripheral circulation, and health-related quality of life (QOL) in disabled older patients with intermittent claudication.\n Prospective, randomized controlled trial.\n University Medical (Center and Veterans Affairs Medical Center, Baltimore, Maryland.\n Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise rehabilitation and 30 to usual-care control. Three patients from the exercise group and six patients from the control group dropped out, leaving 28 and 24 patients, respectively, completing the study in each group.\n Six months of exercise rehabilitation.\n Treadmill distance walked to onset of claudication and to maximal claudication, ambulatory function, peripheral circulation, perceived QOL, and daily physical activity.\n Compliance with the exercise program was 73% of the possible sessions. Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by 12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood flow by 30% (P < .001). Changes in distance walked to maximal pain correlated with changes in walking economy (r = -.50, P = .013) and changes in maximal calf blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer-derived daily physical activity by 38% (P < .001); this change correlated with the change in distance walked to maximal pain (r = .45, P = .020). These improvements were significantly better than the changes in the control group (P < .05).\n Improvements in claudication following exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy. Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community, which enabled the patients to become more functionally independent.", "nan", "The effects of three months therapy with Pentoxifylline (800 mg three times daily) and physical training were compared in two age- and sex-matched groups of Stage II PAOD patients. Before therapy and after 12 and 13 weeks each patient underwent a standard treadmill test. The maximum walking time, TcPO2 half recovery time to basal values after the induced ischaemia, granulocyte production of free radicals (by the superoxide dismutase-inhibitable reduction of ferricytochrome) and surface expression of the CD11/CD18 complex of adhesion molecules (by using specific monoclonal antibodies) were determined. Pentoxifylline inhibited free radical production and reduced the percentage of granulocytes expressing adhesion receptors while exercise had no significant effect on these parameters. These changes, which reflect improved microcirculatory functioning, were associated with a greater walking capacity and shorter half recovery time (+14% vs exercise group, p < 0.01; -39% vs exercise group, p < 0.01 respectively).", "Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function.", "To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training.\n Case-control study: prospective randomised-controlled trial of exercise training.\n Plasma fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR) were measured in 67 claudicants and 15 controls. Twenty-two patients were randomised to supervised exercise training and 17 randomised to observation. Subjects were reviewed at 3, 6 and 12 months.\n The median (interquartile range) baseline fibrinogen was 3.7 g/l (3.3-4.25) in claudicants and 3.5 g/l (2.9-3.95) in controls (p = 0.045); CRP was 4.7 mg/l (2.2-9.0) and 2.1 mg/l (1.0-2.8), respectively (p < 0.0001); SAA was 72 mg/l (35-132) and 30 mg/l (20-89) (p = 0.0009). Claudicants showed an increased urinary ACR following treadmill exercise (Wilcoxon, p < 0.0001) with no change in controls. Exercise training reduced SAA at 6 months, CRP at 3 months and progressively attenuated the post-exercise increase in ACR. No similar changes were found in controls.\n Repetitive low-grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins. Exercise training is associated with symptomatic improvement and reduction inflammatory markers. The concern that exercise has adverse systemic effects therefore seems to be unjustified.", "To investigate the effects of a 24-week program of upper- and lower-limb aerobic exercise training on walking performance in patients with symptomatic peripheral arterial disease (PAD) and to study the mechanisms that could influence symptomatic improvement.\n After approval from the North Sheffield Local Research Ethics Committee, 104 patients (median age, 69 years; range, 50 to 85 years) with stable PAD were randomized into an upper- or lower-limb aerobic exercise training group (UL-Ex or LL-Ex), or to a nonexercise training control group. Training was performed twice weekly for 24 weeks at equivalent relative exercise intensities. An incremental arm- and leg-crank test (ACT and LCT) to maximum exercise tolerance was performed before and at 6, 12, 18, and 24 weeks of the intervention to determine peak oxygen consumption (VO(2)). Walking performance, defined as the claudicating distance (CD) and maximum walking distance (MWD) achieved before intolerable claudication pain, was assessed at the same time points by using a shuttle-walk protocol. Peak blood lactate concentration, Borg ratings of perceived exertion (RPE) and pain category ratio (CR-10) were recorded during all assessments.\n CD and MWD increased over time (P < .001) in both training groups. At 24 weeks, CD had improved by 51% and 57%, and MWD had improved by 29% and 31% (all P < .001) in the UL-Ex and LL-Ex groups, respectively. An increase in peak heart rate at MWD in the UL-Ex group (109 +/- 4 vs 115 +/- 4 beats/min; P < .01) and LL-Ex group (107 +/- 3 vs 118 +/- 3 beats/min; P = .01) was accompanied by an increase in the amount of pain experienced in both groups (P < .05), suggesting that exercising patients could tolerate a higher level of cardiovascular stress and an increased intensity of claudication pain before test termination after training. Patients assigned to exercise training also showed an increase in LCT peak VO2 at the 24-week time point in relation to baseline (P < .01) and control patients (P < .01), whereas ACT peak VO2 was only improved in the UL-Ex group (P < .05).\n Our results suggest that a combination of physiologic adaptations and improved exercise pain tolerance account for the improvement in walking performance achieved through upper-limb aerobic exercise training in patients with PAD. Furthermore, that both arm- and leg-crank training could be useful exercise training modalities for improving cardiovascular function, walking performance, and exercise pain tolerance in patients with symptomatic PAD.", "To explore the efficacy of cycle training in the treatment of intermittent claudication, the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication.\n Forty-two individuals with peripheral arterial disease and intermittent claudication (24 men, 18 women) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then randomized to a treadmill (n = 13), cycle (n = 15), or control group (n = 14). Treadmill and cycle groups trained three times a week for 6 weeks, whereas the control group did not train during this period. Maximal and pain-free exercise times were measured on graded treadmill and cycle tests before and after training.\n Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. Cycle training significantly improved maximal cycle time but did not improve treadmill performance. However, there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline. There was also considerable variation in the training response to cycling, and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group.\n These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise.", "nan", "The prothrombotic, hypofibrinolytic state that develops in patients with intermittent claudication (IC) upon walking due to ischemia-reperfusion injury (IRI) of the leg muscles may contribute to the high incidence of life- and limb-threatening thrombotic events observed in this patient group. Treatments, such as angioplasty, that obtund the IRI also ameliorate the procoagulant diathesis. The effect on this diathesis of supervised exercise and cilostazol, both of which provide symptomatic benefit in IC, but without significantly obtunding IRI, is unknown.\n Thirty-four patients (27 men and 7 women; median age, 67 years; range, 63-72 years) were randomized to receive best medical therapy (BMT) plus supervised exercise (n = 9), BMT plus cilostazol (n = 9), BMT plus supervised exercise plus cilostazol (n = 7), or BMT alone (n = 9) in a 2 x 2 factorial design. Thrombin-antithrombin complex and prothrombin fragments 1 and 2, both markers of thrombin generation; plasminogen activator inhibitor antigen and tissue plasminogen activator antigen, both markers of fibrinolysis; ankle-brachial pressure index (ABPI); and initial and absolute claudication distance (ACD) were measured at baseline and then 3 and 6 months after randomization.\n At 6 months, when compared with receiving BMT only, supervised exercise and cilostazol resulted in improvements in ABPI of 18% and 13% and in ACD of 40% and 64%, respectively. The effects on ABPI and ACD of combining supervised exercise and cilostazol were additive. Supervised exercise, cilostazol, and supervised exercise combined with cilostazol had no significant effect on any of the four hemostatic markers.\n Treatment of IC by supervised exercise or cilostazol results in significant improvements in ABPI and ACD but has no demonstrable effect on the prothrombotic diathesis. This suggests that supervised exercise and cilostazol, unlike angioplasty, are unlikely to have a long-term beneficial effect on the thrombotic risks faced by these patients.", "The purpose of this investigation was to evaluate the efficacy of PoleStriding exercise (a form of walking that uses muscles of the upper and lower body in a continuous movement similar to cross-country skiing) and vitamin E (alpha-tocopherol) to improve walking ability and perceived quality of life (QOL) of patients with claudication pain secondary to peripheral arterial disease (PAD).\n Fifty-two subjects were randomized into four groups: PoleStriding with vitamin E (N = 13), PoleStriding with placebo (N= 14), vitamin E without exercise (N= 13), and placebo without exercise (N = 12). The dose of vitamin E was 400 IU daily. Only the PoleStriding with vitamin E and PoleStriding with placebo groups received PoleStriding instruction and training. Assignment to vitamin E or placebo was double blind. Subjects trained three times weekly for 30-45 min (rest time excluded). Individuals in vitamin E and placebo groups came to the laboratory biweekly for ankle blood-pressure measurements.\n Results of this randomized clinical trial provide strong evidence that PoleStriding significantly (P< 0.001) improved exercise tolerance on the constant work-rate and incremental treadmill tests. Ratings of perceived claudication pain were significantly less after the PoleStriding training program (P= 0.02). In contrast, vitamin E did not have a statistically significant effect on the subjects' ratings of perceived leg pain (P= 0.35) or treadmill walking duration ( P= 0.36). Perceived distance and walking speed (Walking Impairment Questionnaire) and perceived physical function (Rand Short Form-36) improved in the PoleStriding trained group only (P< 0.001, 0.022 and 0.003, respectively).\n PoleStriding effectively improved the exercise tolerance and perceived QOL of patients with PAD. Little additional benefit to exercise capacity was realized from vitamin E supplementation.", "nan", "Treadmill training in claudication is often based on walking exercise to a pain threshold or longer to the maximum muscle pain of the lower limbs. This kind of exercise may cause an inflammatory response. The purpose of this study was to determine whether pain-free treadmill training using walking exercise to 85% of the distance to onset of claudication pain can significantly improve pain-free walking distance in patients with intermittent claudication and to evaluate whether this kind of program may induce an inflammatory response leading to the progression of atherosclerosis.\n A total of 98 patients aged 50-70 yrs with stable intermittent claudication were randomized into a supervised treadmill training program or a comparison group. Patients in the treatment group participated in 12 wks of supervised treadmill training. We examined the effects of 12 wks of pain-free treadmill training on pain-free walking distance, total leukocyte count, neutrophil count, and microalbuminuria in patients with claudication.\n A total of 80 participants completed the program. Exercise rehabilitation increased the time to onset of claudication pain by 119.2%, from 87.4 +/- 38 m to 191.6 +/- 94.8 m (P < 0.001). There was no increase in total leukocyte count, neutrophil count, or microalbuminuria after 12 wks of treadmill exercise (P > 0.05)\n A pain-free training program can be used in the treatment of claudication as a low-risk program, increasing walking ability without potential harmful effects of ischemia-reperfusion injury.", "To assess the effect of pain-free treadmill training on red blood cell deformability and walking distance in patients with claudication.\n Randomized-controlled trial of exercise training.\n Patients were recruited from the primary care, vascular outpatient clinic.\n A total of 60 patients with peripheral arterial occlusive disease (stage II according to Leriche-Fontaine) were randomized into the treadmill program or a control group. Fifty-five patients completed the study (27 in the exercising group and 28 in the control group).\n Patients in the exercising group were walking on the treadmill 3 times a week for 3 months. Each session consisted of 1 hour repetitive walking [performed to 85% of the pain-free walking time (PFWT)] was supervised by a qualified physiotherapist.\n Changes in erythrocyte deformability and treadmill walking performance (PFWT, maximal walking time) were assessed in both groups before the study and after 3 months.\n After 3 months of treadmill training, red blood cell deformability in the exercising group significantly increased (P<0.01). No significant changes were seen in the erythrocyte deformability in the control group. PFWT was prolonged by 102% from 191+/-34 to 386+/-60 seconds (P<0.01), and maximal walking time increased by 49% from 438+/-62 to 656+/-79 seconds (P<0.01) in the exercising group, whereas these changes were insignificant in the control group.\n A significant improvement of walking ability over 3 months of pain-free treadmill training is associated with a significant increase in red cell deformability in patients with claudication.", "nan", "Patients with symptomatic peripheral arterial occlusive disease have a claudication-limited peak exercise performance that is improved with exercise training. The effects of training on skeletal muscle metabolism were evaluated in 26 patients with claudication, randomized into a 12-wk program of treadmill training (enhances muscle metabolic activity in normal subjects), strength training (stimulates muscle hypertrophy in normal subjects), or a nonexercising control group. Gastrocnemius muscle biopsies were performed at rest and before and after training. After 12 wk, only treadmill training improved peak exercise performance and peak oxygen consumption. Treadmill training did not alter type I or type II fiber area and did not increase citrate synthase activity but was associated with an increase in the percentage of denervated fibers (from 7.6 +/- 5.4 to 15.6 +/- 7.5%, P < 0.05). Improvement in exercise performance with treadmill training was associated with a correlative decrease in the plasma (r = -0.67) and muscle (r = -0.59) short-chain acylcarnitine concentrations (intermediates of oxidative metabolism). Patients in the strength and control groups had no changes in muscle histology or carnitine metabolism, but strength-trained subjects had a decrease in citrate synthase activity. Thus treadmill training increased peak exercise performance, but this benefit was associated with skeletal muscle denervation and the absence of a \"classic\" mitochondrial training response (increase in citrate synthase activity). The present study confirms the relationship between skeletal muscle acylcarnitine content and function in peripheral arterial occlusive disease, demonstrating that the response to treadmill training was associated with parallel improvements in intermediary metabolism.", "The efficacy of physical training alone or combined with antiplatelet therapy (dipyridamole and aspirin) was studied in 30 patients with stage II peripheral arterial occlusive disease (PAOD). Patients were randomly allocated to one of the following groups: Group A--dipyridamole 75 mg three times daily and aspirin 330 mg once daily: Group B--physical exercise; Group C--physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily. After six months' treatment the pain-free walking time (PFWT) and the maximum walking time (MWT) improved significantly (p less than 0.05) in all three groups. In group A the PFWT lengthened by 35% (from 101.00 +/- 34.56 to 137.32 +/- 40.50 s) and the MWT by 38% (from 150.34 +/- 55.60 to 207.26 +/- 60.67 s); in group B the PFWT lengthened by 90% (from 90.65 +/- 40.54 to 171.45 +/- 55.60 s) and the MWT by 86% (from 145.39 +/- 60.50 to 270.63 +/- 63.61 s). When physical exercise was associated with drugs as in group C, the PFWT lengthened by 120% (from 89.51 +/- 43.89 to 196.72 +/- 51.73 s) and the MWT by 105% (from 160.43 +/- 59.84 to 329.05 +/- 63.96 s). No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after standard treadmill exercise, in the plethysmographic rest and peak flows, or in the transcutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia. The results confirm the benefits of regular exercise in stage II PAOD patients but suggest they may be enhanced by antiplatelet therapy.", "This study reports the initial evaluation of treatment efficiency in 75 patients with intermittent claudication who were randomized to three treatment groups: 1) reconstructive surgery, 2) reconstructive surgery with subsequent physical training, and 3) physical training alone. Before treatment, there were no statistically significant differences between the groups in age, sex, smoking habits, symptom duration of claudication, ankle-arm blood pressure quotient (ankle-index), maximal plethysmographic calf blood flow, symptom-free and maximal walking distance, the history of other atherosclerotic manifestations or in the medical treatment. The walking performance was improved in all three groups at follow-up 13 +/- 0.5 months after randomization. Surgery was most effective, but the addition of training to surgery improved the symptom-free walking distance even further. In pooled observations of the three groups, age, symptom duration, and a history of myocardial ischemic disease correlated negatively with walking performance after treatment. In the operated group, the duration of claudication and a history of myocardial ischemic disease correlated negatively with the walking performance. This was not the case when patients were censored if limited by other symptoms than intermittent claudication after treatment. In the trained group, the duration of claudication correlated negatively to symptom-free and maximal walking distance. Ankle-index and maximal plethysmographic calf blood flow after treatment and the change of these variables with treatment correlated positively with both symptom-free and maximal walking distance when results were pooled for all patients. Although this mainly was a consequence of the improved blood flow after surgery, the change of maximal plethysmographic calf blood flow also correlated with symptom-free but not with maximal walking distance in the trained group. The results demonstrate that, compared with physical training alone, operation alone or in combination with subsequent training are superior treatment modalities in patients with intermittent claudication.", "to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. Design: prospective, randomised study.\n a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis.\n invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure.\n invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.\n Copyright 2001 Harcourt Publishers Limited.", "To compare the effect of unsupervised exercise, supervised exercise and intermittent pneumatic foot and calf compression (IPC) on the claudication distance, lower limb arterial haemodynamics and quality of life of patients with intermittent claudication.\n Thirty-four eligible patients with stable intermittent claudication were randomised to IPC (n = 13, 3h/d for 6 months), supervised exercise (n = 12, three hourly sessions/week for 6 months) or unsupervised exercise (n = 9). In each patient, initial claudication distance (ICD), absolute claudication distance (ACD), resting ankle brachial pressure index (ABPI), and resting hyperaemic calf arterial inflow were measured before, 6 weeks, 6 months and 1 year after randomisation. Quality of life was assessed with the short form (SF)-36, walking impairment (WIQ) and intermittent claudication questionnaires (ICQ).\n Compared with unsupervised exercise, both IPC and supervised exercise, increased ICD and ACD, up to 2.83 times. IPC increased arterial inflow (p < 0.05 at 6 weeks) and ABPI. Supervised exercise decreased arterial inflow and increased ABPI (p < 0.05 at 6 months). Unsupervised exercise had no effect on arterial inflow or ABPI. IPC improved significantly the ICQ score and the speed score of the WIQ, while supervised exercise improved the WIQ claudication severity score. At 1 year clinical effectiveness of supervised exercise and IPC was largely preserved.\n IPC, by augmenting leg perfusion, achieved improvement in walking distance comparable with supervised exercise. Long-term results in a larger number of patients will provide valuable information on the optimal treatment modality of intermittent claudication.", "To determine the effects of 12-week exercise programme on ambulatory function, free-living daily physical activity and health-related quality of life in disabled older patients with intermittent claudication.\n Prospective, randomized controlled trial.\n University Medical Center and Veterans Affairs Medical Center, Taipei, Taiwan.\n Thirty-two of 64 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise training and 32 to usual care control. Five patients from the exercise group and six patients from the control group dropped out, leaving 27 and 26 patients, respectively, completing the study in each group.\n Twelve weeks of treadmill exercise training.\n Treadmill walking time to onset of claudication pain and to maximal claudication pain, 6-min walk distance, self-reported ambulatory ability and perceived health-related quality of life (QOL).\n Compliance of exercise programme was 83% of the possible sessions. Exercise training increased treadmill walking time to onset of claudication pain by 88% (P < 0.001), time to maximal pain by 70% (P < 0.001), and 6-min walk distance by 21% (P < 0.001).\n Perception of health-related QOL improved from 12% to 178% in the exercise group. These improvements were significantly better than the changes in the control group (P < 0.05).\n Significant improvements in claudication following 12-week exercise training in elderly PAOD patients were observed. Increase in treadmill walking time to maximal claudication pain in these patients translated into the improvement of perceived physical health, which enabled the patients to become more functionally independent." ]

[ "10937118", "16804456", "9811023", "12390375", "2696870", "15450839", "11722525", "11485582", "17661940", "17394707" ]

[ "Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty. A prospective controlled study of wound-healing characteristics.", "A prospective, randomized controlled trial comparing n-butyl cyanoacrylate tissue adhesive (LiquiBand) with sutures for skin closure after laparoscopic general surgical procedures.", "Use of octyl-2-cyanoacrylate for skin closure in facial plastic surgery.", "Randomized study of the effectiveness of closing laparoscopic trocar wounds with octylcyanoacrylate, adhesive papertape or poliglecaprone.", "A clinical trial of tissue adhesive (histoacryl) in skin closure of groin wounds.", "Closure of long surgical incisions with a new formulation of 2-octylcyanoacrylate tissue adhesive versus commercially available methods.", "Prospective randomized blind controlled trial comparing sutures, tape, and octylcyanoacrylate tissue adhesive for skin closure after phlebectomy.", "Butylcyanoacrylate tissue adhesive for columellar incision closure.", "A randomized controlled trial of high-viscosity 2-octyl cyanoacrylate tissue adhesive versus sutures in repairing facial wounds following Mohs micrographic surgery.", "A blinded, randomised, controlled trial of stapled versus tissue glue closure of neck surgery incisions." ]

[ "To compare the surgical efficacy and wound-healing characteristics of the tissue adhesive octyl-2-cyanoacrylate (approved by the Food and Drug Administration) with traditional suture closure in upper blepharoplasty.\n Prospective, randomized, blinded study comparing cosmetic and functional outcome and time efficiency. Twenty subjects underwent upper eyelid blepharoplasty. Each patient had a control side and an experimental side determined randomly. One eyelid incision was closed with octyl-2-cyanoacrylate (Dermabond; Ethicon Inc, Somerville, NJ) tissue glue, and the other with 6.0 suture (polypropylene or fast-absorbing gut). Comparisons were performed for the time for closure by each method, wound healing, and patient satisfaction. Macrophotographs of the wounds at 1, 2, and 4 weeks after surgery were graded by 5 observers blinded to the closure method, using a 10-point scale and a modified Hollander wound evaluation scale.\n No statistically significant difference was found between the quality of octyl-2-cyanoacrylate closure and suture closure at 1 month. There were no differences in wound complications, duration of healing, inflammation, or final incision appearance. By 2 weeks, the sides were indistinguishable in 15 (75%) of the patients. Time for closure averaged 7 minutes with suture and 8 minutes with glue.\n Octyl-2-cyanoacrylate glue is an excellent alternative to suture closure, producing equivalent quality of closure at all time points and no difference in appearance. This adhesive was sufficient to withstand the forces of closure in upper eyelid blepharoplasty without dehiscence in the absence of sutures.", "The aim of this study was to compare the efficacy of n-butyl-cyanoacrylate tissue adhesive (Liquiband) with nonabsorbable monofilament sutures for laparoscopic port site closure. Adult patients having elective laparoscopic procedures were randomly allocated to wound closure with sutures or tissue adhesive. End points included skin closure time, wound dressing requirements, wound complications, and cosmesis, assessed at discharge, 4 to 6 weeks and 3 months. Seventy-eight patients randomized to receive sutures and 76 to receive tissue adhesive were eligible for final analysis. Mean closure time was significantly longer for sutures (220 vs. 125 s, P < 0.001). Fewer dressings were required in the tissue adhesive group immediately postoperatively (21% vs. 97%, P < 0.001) and at discharge (24% vs. 82%, P < 0.001). There were no significant differences in wound complications or in cosmesis at either 4 to 6 weeks or at 3 months. Tissue adhesive for laparoscopic port site closure offers potential savings with respect to time and has comparable wound complication rates and cosmetic outcomes when compared with nonabsorbable monofilament sutures.", "Octyl-2-cyanoacrylate is a long carbon chain cyanoacrylate derivative that is stronger and more pliable than its shorter chain derivatives. One hundred and eleven patients underwent elective surgical procedures by the same surgeon using either octyl-2-cyanoacrylate or sutures for skin closure at the University of Illinois at Chicago. Most patients underwent excision of benign skin lesions with a mean wound size of 112 mm3. Patients were randomized into either control (vertical mattress suture closure) or test groups (closure with octyl-2-cyanoacrylate). Surgical judgment was used to determine which wounds in each group required application of subcutaneous sutures to relieve tension and aid in skin edge eversion. Generally, full-thickness (through dermis) wounds larger than 1 cm3 required the use of subcutaneous sutures. The time required to close the epidermis with suture (mean, 3 minutes and 47 seconds) was about four times that of octyl-2-cyanoacrylate (mean, 55 seconds). Wounds were evaluated at 5 to 7 days for infection, wound dehiscence, or tissue reaction, and at 90 days using the modified Hollander wound evaluation scale. At 1 year, photographs of the wounds were evaluated by two facial plastic surgeons that graded the cosmetic outcome using a previously validated visual analog scale. There were no instances of wound dehiscence, hematoma, or infection in either group. Results of wound evaluation at 90 days determined by the modified Hollander scal revealed equivalent cosmetic results in both groups. Results of the visual analog scale ratings showed scores of 21.7 +/- 16.3 for the 49 patients treated with octyl-2-cyanoacrylate and 29.2 +/- 17.7 for the 51 control patients treated with sutures. The lower visual analog scale score represented a superior cosmetic outcome at 1 year with the octyl-2-cyanoacrylate as compared with sutures. This difference is statistically significant at p = 0.03. Additionally, patient satisfaction was very high in the group treated with octyl-2-cyanoacrylate.", "Several methods for skin closure are used, i.e. sutures, adhesive papertape and tissue adhesives. Little is known about the efficacy of these techniques in laparoscopic surgery. This study was performed to analyse the efficacy of octylcyanoacrylate, a new tissue adhesive, adhesive papertape and poliglecaprone for wound closure in laparoscopy.\n From May 2000 to September 2001, 140 patients were included in a prospective randomized trial. Wounds were closed with octylcyanoacrylate (n = 48), adhesive papertape (n = 42) or poliglecaprone (n = 50). Closing time, wound infection, cosmetic results and costs were evaluated. A time-motion analysis was also performed.\n The patients in the three groups were well matched for age, gender and body mass index. Closing times per wound were 26, 33 and 65 s respectively for adhesive papertape, octylcyanoacrylate and poliglecaprone (P < 0.001). Cosmetic results, as scored by the patients, were no different. The number of actions required to close each wound was 5.7, 8.3 and 21.0 for octylcyanoacrylate, adhesive papertape (P = 0.05 versus octylcyanoacrylate) and poliglecaprone (P < 0.01 versus octylcyanoacrylate and adhesive papertape) respectively. Octylcyanoacrylate was significantly more expensive than poliglecaprone and adhesive papertape.\n Closure with adhesive papertape was the fastest method. The smallest number of actions required to close a wound was with octylcyanoacrylate. Adhesive papertape was the most cost-effective.", "The use of tissue adhesives has been widely studied since the 1960s. Since then they have found use in specialties like plastic surgery, neurosurgery, ENT surgery and dental surgery. Several papers have reported their safe use, both clinically and experimentally, particularly of the newer homologue n-butyl/2-cyanoacrylate (Histoacryl). In this study 43 patients (46 wounds) whose operations involved a groin incision were randomised into two groups for skin closure either with Dexon subcuticular suture (23 wounds) or Histoacryl glue (23 wounds). We found that both sets of wounds healed well with no wound infections or excessive inflammation when assessed at one week and four weeks. However the glued wounds had consistently better cosmesis scores (mean score 4.71 at four weeks) compared to the subcuticular Dexon wounds (mean score 4.00 at four weeks) and P value of less than 0.05. We feel that there is a place for tissue adhesives in skin closure for some general surgical wounds.", "Topical 2-octylcyanoacrylate tissue adhesive is an alternative to traditional devices for closing short surgical incisions.\n An open-label, randomized study compared a new high-viscosity formulation of 2-octylcyanoacrylate with commercially available devices, including low-viscosity 2-octylcyanoacrylate, for epidermal closure of incisions > or = 4 cm requiring subcutaneous and/or deep-dermal suturing.\n Of patients with 1 to 3 wounds, 106 were treated with high-viscosity 2-octylcyanoacrylate and 103 with commercially available devices. The day-10 rates of healing by wound were 96% and 97% for study versus control treatment and 97% and 95% for new and old 2-octylcyanoacrylate formulations versus other controls, respectively. Day-10 infection rates by wound were 4 of 145 versus 7 of 131 for study versus control treatment and 6 of 207 and 5 of 69 for new and old 2-octylcyanoacrylate versus other controls, respectively.\n The new tissue adhesive formulation provides epidermal wound closure equivalent to commercially available devices with a trend to decreased incidence of wound infection.\n Copyright 2004 Excerpta Medica, Inc.", "The patient's view of the outcome after phlebectomy is mainly dependent on the cosmetic result.\n To compare 5-0 monofilament sutures with tapes and tissue adhesive for wound closure after varicose vein surgery.\n Seventy-nine patients undergoing varicose vein surgery were prospectively randomized in three groups (tissue adhesive, sutures, tape) for skin closure and compared. The follow-up 1 year postoperatively was done by a senior dermatologist who was blinded in the method of skin closure.\n The cosmetic outcome showed little advantage for the suture group. Taping the incisions is faster than suturing them but without significance; closure with tissue adhesive takes nearly the double of time. The closure for one incision with tissue adhesive is 40 times more expensive than with tapes and 14 times more expensive than with sutures.\n This study failed to demonstrate an advantage of tissue adhesive and tapes over monofilament sutures for skin closure after phlebectomy.", "Cosmetic outcome of the columellar incision closure in external rhinoplasty patients has been a subject of discussion. This study was conducted to assess whether tissue adhesives provide an alternative option for sutureless closure of columellar skin incisions for cases utilizing open technique rhinoplastic surgery. One hundred and one patients undergoing external rhinoplasty were randomized to either topical application of butylcyanoacrylate or polypropylene sutures for columellar skin closure. The majority of tension on the wound edges was taken up using 5-0 chromic catgut. Cosmetic outcomes were evaluated by two otolaryngologists independently using visual analogue and Hollander wound evaluation scales in a blinded manner. There was no statistically significant difference in cosmesis between the surgeons' evaluation scores for either type or repair of the columellar incision. Since the tissue adhesive forms its own protective barrier, post-operative care is simplified. Closure with adhesives eliminates the need for post-operative suture removal requiring an extra visit that should lead to more efficient use of physician and patient time. Butylcyanoacrylate performs cosmetically as well as standard suture closure of columellar skin incision used for external rhinoplasty.", "High-viscosity 2-octyl cyanoacrylate (HVOCA) is a rapidly polymerizing liquid topical adhesive indicated for epidermal approximation of superficial lacerations and surgical wounds. Use of HVOCA in repair of facial wounds after Mohs micrographic surgery (MMS) has not been reported.\n To compare aesthetic outcome of HVOCA versus sutured epidermal closure of linearly repaired facial wounds following MMS.\n Patients undergoing MMS for facial tumors with postoperative wounds >3 cm appropriate for linear closure were recruited. After placement of dermal sutures, half the wound was randomly selected for closure with HVOCA and the other half was closed with 5-0 polypropylene suture.\n Fourteen patients (13 men and 1 woman; mean age, 72+/-8.8 years; range, 52-81 years) with basal cell or squamous cell carcinoma of the face (n=12) or neck (n=2) were enrolled. The mean wound length was 4.9+/-1.9 cm (range, 3.1-10 cm). No postoperative complications, including bleeding, infection, or dehiscence, occurred. Using photographs obtained 3 months postoperatively, five dermatologists (including two Mohs surgeons) blinded to the intervention rated cosmesis using a visual analog scale from 1 (worst) to 10 (best). The mean ratings for HVOCA half (6.64+/-1.55) versus sutured half (6.77+/-1.88) were not significantly different (p=.35). Paired comparisons of rater preferences similarly showed no cosmetic differences. All 14 patients preferred OCA for ease of postoperative care.\n HVOCA tissue adhesive is cosmetically equivalent to epidermal sutures in the linear repair of facial wounds following MMS. This technique represents an additional option for Mohs surgeons.", "Cosmetic acceptability of scar and neck mobility are important outcomes after collar line incision for neck surgery. This randomised, controlled trial compares these parameters in closures using tissue glue (Dermabond, Ethicon, UK) and skin staples.\n Patients requiring a collar line incision were randomised to receiving tissue glue or staples for skin closure. Time for closure to be completed was recorded. Mobility of the neck was assessed using a visual analogue scale at 48 h and 1 week after surgery. At 6 weeks, cosmetic appearance was assessed using a linear 1-10 visual analogue scale by the patient, surgeon and an independent blinded assessor. Results were compared using appropriate statistical tests.\n Glued (n = 14) and stapled (n = 15) closures were performed for hemithyroidectomy (n = 8 versus 6), sub-total thyroidectomy (n = 2 versus 4), total thyroidectomy (n = 1 versus 4) and parathyroidectomy (n = 3 versus 1). Closure with tissue glue took significantly longer than with staples (mean, 95 versus 28 s; P < 0.001). Neck mobility scores were comparable at 48 h and 1 week (mean, 4.8 versus 4.4; P = 0.552: and 2.7 versus 2.6; P = 0.886). Cosmetic appearance at 6 weeks was comparable when patient (mean, 1.7 versus 1.8; P = 0.898), surgeon (mean, 2.6 versus 2.3; P = 0.633) and independent assessment (mean, 1.4 versus 1.9; P = 0.365) was performed.\n The use of glued skin closure may increase the duration of surgery but acceptable neck mobility and wound cosmesis can be achieved by the more rapid application of stapled skin closure in cervicotomy incisions." ]

[ "3890520", "10853619", "2181103", "7347217", "7310594", "19926098" ]

[ "Limitations of theophylline in the treatment of apnea of prematurity.", "Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study.", "A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity.", "Theophylline in treatment of apnoea of prematurity.", "The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants.", "Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups." ]

[ "Theophylline is commonly used to treat apnea of prematurity. To determine the effectiveness of theophylline with respect to gestational and postnatal age, we conducted a controlled study in 43 premature infants with idiopathic apnea. Three of the 21 treated and eight of the 22 control infants developed respiratory failure. Eight of the 11 infants with respiratory failure had gestational ages of less than 31 weeks and had more than four apneic episodes during the first day of life. In the treated infants without respiratory failure, the number of apneic episodes by 24-hour intervals declined six days earlier than in the control infants. Apnea disappeared, however, at a similar time in both groups. Three treated infants and three control infants had apneic episodes persisting beyond the neonatal period. Patients treated with theophylline did not develop respiratory failure as often as control infants did. However, despite a reduction of apneic episodes, theophylline did not shorten the course of apnea of prematurity.", "To evaluate the efficacy and safety of caffeine citrate for treatment of apnea of prematurity.\n Multicenter, parallel, randomized, double-blind, placebo-controlled trial with open-label rescue.\n Nine neonatal intensive care units.\n Eighty-five infants, 28-32 weeks postconception and 24 hours or more after birth who had six or more apnea episodes within 24 hours.\n Caffeine citrate 10 mg/kg (as caffeine base) administered intravenously, followed by 2.5 mg/kg/day orally or intravenously, or placebo, for up to 10 days. Infants failing double-blind therapy could receive open-label rescue.\n Success was defined as 50% or greater reduction in apnea episodes and elimination of apnea. Caffeine citrate was significantly more effective than placebo in reducing apnea episodes by at least 50% in 6 days (p<0.05), and approached statistical significance (p<0.10) in 3 days. It was significantly better than placebo in eliminating apnea in 5 days (p<0.05), and approached significance (p<0.10) in 2 days. The number of infants with an aggregate of 7-10 days of at least a 50% reduction in apnea events or elimination of apnea was significantly higher in the caffeine citrate than in the placebo group. Adverse events did not differ significantly between groups. No correlations were found between success and mean daily plasma concentrations or baseline characteristics. Volume of distribution and clearance increased with weight, supporting weight-adjusted dosing of caffeine citrate.\n Caffeine citrate 10 mg/kg caffeine base (equivalent to 20 mg/kg caffeine citrate) intravenously followed by 2.5 mg/kg/day caffeine base (equivalent to 5 mg/kg/day caffeine citrate) either intravenously or orally for 10 days is safe and effective for treating apnea of prematurity in infants 28-32 weeks postconception.", "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.", "nan", "This prospective controlled study was aimed at evaluating the efficacy of caffeine in treating recurrent idiopathic apnea in the premature infant. Eighteen preterm infants (29 to 35 weeks' gestation) were studied. Recordings during the first 24 hours and on the fifth day of caffeine treatment showed a significant decrease of severe apnea (P less than 0.01) and of mild apnea (P less than 0.001) in the treated group (group 1) as compared with the control group (group II). No treatment of apnea other than caffeine was required in group I, whereas six neonates in group II had such severe and frequent apneic episodes for more than 48 hours that withholding additional treatment was believed to be unethical. No undesirable side effects of caffeine treatment were observed.", "To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial.\n Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (< or =3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions.\n There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (-0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03).\n There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation.\n Copyright 2010 Mosby, Inc. All rights reserved." ]

[ "1872925", "1473127", "1459169", "8732710", "8112187", "3181646", "12351465", "12399272", "7698053", "8352456", "9125301", "9028717", "2676659", "11247166", "2394967", "16960167", "12421024", "9589230", "8495604", "7825523", "2209315" ]

[ "A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients.", "[The effect of fish oil on the secretion and effect of insulin in patients with type II diabetes].", "Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus.", "A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes.", "Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study.", "Effect of fish oil concentrate on lipoprotein composition in NIDDM.", "Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients.", "Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension.", "A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM.", "The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control.", "Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus.", "Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients.", "Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM.", "[Effects of diet therapy including eiconol on clinical and metabolic parameters in patients with type 2 diabetes mellitus].", "Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus.", "Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation.", "Effects of low-dose omega-3 fatty acid substitution in type-2 diabetes mellitus with special reference to oxidative stress--a prospective preliminary study.", "Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study.", "Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM.", "Dietary supplementation with n-3 fatty acids increases gluconeogenesis from glycerol but not hepatic glucose production in patients with non-insulin-dependent diabetes mellitus.", "Effects of fish oil supplements in NIDDM subjects. Controlled study." ]

[ "Eight male non-insulin-dependent diabetic patients participated in a double-blind randomized cross-over study (2 weeks for each period) evaluating the effects of 10 g/day fish oil dietary supplementation on glucose and lipid metabolism. Fasting serum triglyceride concentrations were decreased by fish oil because of a reduction in VLDL (1.4 +/- 0.2 vs. 1.9 +/- 0.2 mmol/l, P less than 0.025). LDL cholesterol concentration was instead increased (3.4 +/- 0.3 vs. 2.8 +/- 0.3 mmol/l, P less than 0.025) and net changes in VLDL triglyceride and in LDL cholesterol were inversely correlated (r = -0.86, P less than 0.01). Plasma free fatty acids concentrations and turnover rate [( 3H]palmitate method) were similar after fish oil and placebo. Fish oil supplement did not induce significant changes in fasting blood glucose (8.1 +/- 1.1 vs. 8.5 +/- 1.2 mmol/l) and average daily blood glucose (BG) (9.4 +/- 3.2 vs. 9.3 +/- 3.5 mmol/l). Glucose stimulated plasma insulin response during a hyperglycemic clamp was not significantly influenced by fish oil both in the early phase and during steady state. Insulin sensitivity (M/I index) was also unchanged. In conclusion, this study shows that a dietary supplement of fish oil decreases plasma triglyceride levels in non-insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change. With this dosage of fish oil no relevant variations in glycemic control, insulin secretion and insulin sensitivity occurred.", "The metabolic effect of 3-week dietary supplementation with a fish oil concentrate was examined in not markedly obese, not hypertriglyceridemic men with non-insulin-dependent diabetes mellitus (NIDDM) treated with hypoglycemic agents. Ten patients were given 15 ml/d of fish oil (Martens Oil, Norway) equivalent to 3.1 g of n-3 fatty acid (FA) per day, and compared to 10 diabetics treated with placebo (15 ml/d saline). While fish oil leads to expected increase in the ratio of n-3 to n-6 FA intake, it does not alter fasting and mixed meal stimulated blood glucose, plasma insulin and C-peptide concentrations. There were no changes in insulin action estimated by the metabolic clearance rates of glucose at plasma insulin levels of about 100 microU/ml and 1400 microU/ml during hyperinsulinemic isoglycemic clamp, and no changes were seen in insulin binding to erythrocytes. Even though our short-term study does not warrant authoritative conclusions, no adverse effects of low-dose fish oil on glucose homeostasis have been found in not markedly obese NIDDM patients treated with oral hypoglycemics.", "The effects of dietary supplementation with n-3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. The serum triglyceride (TG) concentrations decreased by 27% (P < 0.01) after addition of MaxEPA with a reduction of VLDL TG by 36% (P < 0.05) while LDL cholesterol increased by 6% (P = 0.05). The fasting blood sugar and HbA1c concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period. The highest glucose concentrations at fasting and after an i.v. glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged. The peripheral insulin sensitivity, as measured by a euglycaemic, hyperinsulinaemic clamp technique, did not change during the study. The mean plasminogen inhibitor-1 (PAI-1) activity of the patients was elevated compared with healthy controls. In spite of the reduction of the triglyceride concentrations and unchanged insulin levels, there was a significant increase of the activity of PAI-1 (+21%, P < 0.01) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity. In many situations there seems to be a reduction of PAI-1 when the triglycerides are lowered. In the diabetic patients given n-3 fatty acids this was not the case.", "Supplementation of type II diabetic diets with n-3 fatty acids (FAs) from fish oil (FO) has been associated with lowered triglyceride and VLDL levels, although reports of impaired glycemic control have limited their use. Effects of n-3FAs from nonmarine sources are less well documented. Therefore, an investigation comparing the effects of linseed oil (LO) with FO supplementation was undertaken in subjects with type II diabetes.\n Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a randomized double-blind crossover fashion after 3 months of olive oil placebo. Oils were given as 35 mg FA.kg body wt-1.day-1. After each 3-month period, fasting glucose and insulin levels, HbA1c, lipid profiles, insulin sensitivity (SI), glucose effectiveness (SG), and acute insulin response to glucose (AIRG) were evaluated.\n HbA1c and lipid values were within the normal range at randomization. Repeated measures analysis of variance testing found no significant differences in weight; fasting glucose and insulin levels; HbA1c; total, LDL, and HDL cholesterol levels; SI; SG; or AIRG with either active oil. FO was associated with significant reductions in triglycerides and a trend toward decreased SI.\n In a population with well-controlled type II diabetes, 3 months of FO but not LO resulted in lowered triglyceride levels. Neither LO nor FO significantly affected glycemic control, cholesterol values, SG, or insulin secretion, while a nonsignificant trend toward decreased insulin sensitivity was found with FO.", "To study the effects of a low dose of omega-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus (NIDDM).\n We performed a randomized, prospective, double-blind, controlled study of a low dose of omega-3 fatty acids (2.5 g/day) in 20 ambulatory subjects with NIDDM. Subjects ingested five 1-g fish oil capsules each containing 0.5 g omega-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period.\n Nine subjects completed the study in each group. Both groups exhibited moderate control of glucose levels; modest elevations in baseline total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels; and normal blood pressure values. In the fish oil group, plasma omega-3 fatty acid levels increased significantly. Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil. No difference was observed in collagen-induced production of thromboxane A2 (TXA2, measured as the stable derivative TXB2), or in adenosine-5'-diphosphate- (ADP) induced platelet aggregation or TXA2 generation. Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil. Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure (sBP) by 8 mmHg compared with safflower oil. Fish oil caused a significant but small increase in HbA1c (0.56%) and total cholesterol (20 mg/dl) but had no effect on fasting glucose, high-density lipoprotein cholesterol, or LDL-cholesterol levels.\n Small doses of fish oil inhibit platelet aggregation and TXA2 production, reduce upright sBP and TG levels, and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM. Small quantities of omega-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients.", "Non-insulin-dependent diabetes mellitus (NIDDM) is associated with elevated very-low-density lipoprotein (VLDL) triglyceride concentrations and abnormalities of low-density lipoprotein (LDL) composition. Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects, we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM. Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design. Medications, including antidiabetic therapy, were continued through the study. Compared with safflower oil treatment, fish oil supplementation resulted in a significant reduction of total plasma triglycerides of 24% at the 4-g dose and a larger reduction of 39% at the 7.5-g dose. These decreases were due to similar reductions in VLDL triglycerides. LDL cholesterol levels were mildly elevated, but a larger 20% increase in LDL apolipoprotein B (apoB) concentration was observed. During supplementation with the fish oil concentrate, the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values, but not when compared with safflower oil treatment. High-density lipoprotein (HDL) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment. At the 7.5-g dose, fasting glucose and glycohemoglobin levels increased by 20 and 12%, respectively, but were unchanged at the lower level of supplementation. Thus, in NIDDM patients, dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)", "The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol (TAG), low HDL cholesterol, and a predominance of atherogenic small dense LDLs. Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might, therefore, be a good nonpharmacological treatment for type 2 diabetic patients. In the present study, we investigate the effect of fish oil supplementation on the fasting lipid profile, including LDL and HDL subclasses.\n A total of 42 type 2 diabetic patients were randomized to supplementation (capsules) with 4 g daily of either fish oil (n = 20) or corn oil (n = 22) for 8 weeks preceded by a 4-week run-in period of corn oil supplementation. Blood was drawn before and after the 8-week intervention period. Plasma lipoproteins, including LDL and HDL subclasses, were separated by ultracentrifugation.\n Fish oil lowered TAG (group difference: P = 0.025) and raised HDL-2b cholesterol (P = 0.012) and HDL-2a cholesterol (P = 0.007) concentrations as compared with corn oil. We observed no significant effects of fish oil on LDL cholesterol, HDL cholesterol, or the concentration of small dense LDL particles.\n Fish oil supplementation may partially correct the dyslipidemia of type 2 diabetic patients. However, the putative very important aspect of diabetic dyslipidemia-the predominance of small dense LDL particles-was unaffected by fish oil.", "n-3 Fatty acids lower blood pressure, improve lipids, and benefit other cardiovascular disease risk factors. Effects on glycemia in patients with type 2 diabetes are uncertain.\n We determined whether purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on glycemic control, including insulin sensitivity and stimulated insulin secretion; 24-h ambulatory blood pressure; and serum lipids in type 2 diabetic patients with treated hypertension.\n In a double-blind, placebo-controlled trial of parallel design, 59 subjects were randomly assigned to consume 4 g EPA, DHA, or olive oil/d for 6 wk while continuing to consume their usual diet.\n Thirty-nine men and 12 postmenopausal women with a mean (+/- SE) age of 61.2 +/- 1.2 y completed the study. In comparison with the change from baseline in fasting glucose in the olive oil group, fasting glucose in the EPA and DHA groups increased 1.40 +/- 0.29 mmol/L (P = 0.002) and 0.98 +/- 0.29 mmol/L (P = 0.002), respectively. Neither EPA nor DHA had significant effects on glycated hemoglobin, fasting insulin or C-peptide, insulin sensitivity or secretion, or blood pressure. Serum triacylglycerols in the EPA and DHA groups decreased 19% (P = 0.022) and 15% (P = 0.022), respectively. There were no significant changes in serum total, LDL, or HDL cholesterol, although HDL(2) cholesterol in the EPA and DHA groups increased 16% (P = 0.026) and 12% (P = 0.05), respectively. HDL(3) cholesterol decreased 11% (P = 0.026) with EPA supplementation.\n EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients. The overall implications for cardiovascular disease require long-term evaluation.", "To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM).\n Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks.\n The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure.\n In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.", "Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.", "Lipid peroxidation may be important in the development of cardiovascular disease, a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus (NIDDM). We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde, as thiobarbituric acid reacting substances (TBARS), in 23 non-insulin diabetic patients. Plasma levels of standardised alpha-tocopherol (vitamin E), lipid content of whole plasma and lipoprotein fractions, glycosylated haemoglobin, glycosylated low density lipoprotein (LDL) and fasting blood glucose were also measured. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double blind crossover fashion for 6 weeks followed by a 6 week washout period and a final 6 week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the of the active treatment periods at 6 and 18 weeks. Treatment with olive oil did not change levels of TBARS, vitamin E or indices of glycaemic control compared with baseline. Total cholesterol and triglyceride (TG) content of plasma and lipoprotein fractions were not significantly altered. Treatment with fish oil resulted in elevation of TBARS (P < 0.001) and reduction of vitamin E (P < 0.01) compared with baseline and olive oil treatment. Plasma cholesterol was unchanged. A reduction in plasma TG compared with baseline occurred but failed to reach significance (P =0.07). Changes in apo B containing lipoproteins induced by fish oil failed to reach significance. No significant changes were observed in concentration or composition of high density lipoprotein (HDL). Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance (P = 0.06). Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil. This potentially adverse reaction may limit the therapeutic use of fish oils in such patients.", "This study was conducted to examine the effect of omega 3 fatty acid supplementation on plasma lipid, cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher (0.65, n = 10) or lower (0.44, n = 18) ratio of dietary polyunsaturated to saturated fatty acid (P/S). The participants were initially given an olive oil supplement (placebo) equivalent to 35 mg of 18:1. kg body weight-1.day-1 for 3 months. This was followed by two omega 3 supplement periods in a randomized crossover. In these 3-month periods, participants were given a linseed oil supplement equivalent to 35 mg of 18:3 omega 3.kg body weight-1.day-1 or a fish oil supplement equivalent to 35 mg of 20:5 omega 3 + 22:6 omega 3.kg body weight-1. day-1. At the end of each supplement period, a blood sample was drawn from each participant for lipid, lipoprotein, insulin, glucagon and C-peptide analyses. At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio. Results indicate that fish oil significantly reduced plasma triacylglycerol level (p < 0.05) and increased 20:5 omega 3 and 22:6 omega 3 content of all lipoprotein lipid classes. Linolenic acid supplementation had no effect on plasma triacylglycerol level, but it increased 18:3 omega 3 content of lipoprotein cholesterol ester fractions (p < 0.05). A slight increase in 20:5 omega 3, but not 22:6 omega 3, content was noted in lipoprotein lipid classes as a result of 18:3 omega 3 supplementation. LDL and HDL cholesterol, insulin, glucagon and C-peptide levels were not affected by either omega 3 supplement. It is concluded that a modest intake of omega 3 fatty acids, such as could be obtained from consuming fish regularly, will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels.", "Fish oils, containing omega-3 fatty acids (omega 3FAs), favorably influence plasma lipoproteins in nondiabetic humans and prevent the development of insulin resistance induced by fat feeding in rats. We studied the effects of fish oils in 10 subjects (aged 42-65 yr) with mild non-insulin-dependent diabetes mellitus (NIDDM). Subjects were fed a standard diabetic diet plus 1) no supplementation (baseline), 2) 10 g fish oil concentrate (30% omega 3FAs) daily, and 3) 10 g safflower oil daily over separate 3-wk periods, the latter two supplements being given in radom order by use of a double-blind crossover design. At the end of each diet period, fasting blood glucose (FBG), insulin, and lipids were measured, and insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp performed with [3-3H]glucose. FBG increased 14% during fish oil and 11% during safflower oil supplementation compared with baseline (P less than .05), whereas body weight, fasting serum insulin levels, and insulin sensitivity were unchanged. The absolute increase in FBG during each supplementation period correlated with the baseline FBG (fish oil, r = .83, P less than .005); safflower oil, r = .75, P = .012). Fasting plasma triglyceride levels decreased during fish oil supplementation in the 4 subjects with baseline hypertriglyceridemia (greater than 2 mM) but were not significantly reduced overall. There was no significant change in fasting plasma total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. In summary, dietary fish oil supplementation adversely affected glycemic control in NIDDM subjects without producing significant beneficial effects on plasma lipids. The effect of safflower oil supplementation was not significantly different from fish oil, suggesting that the negative effects on glucose metabolism may be related to the extra energy or fat intake.(ABSTRACT TRUNCATED AT 250 WORDS)", "It was investigated the influence of a diet supplemented with PUFA omega-3 (\"Eiconol\") on dynamic of basal and postprandial glycemia, blood pressure, lipid levels, parameters of lipid peroxidation in 60 patients with non-insulin-dependent diabetes mellitus. Fish oil (\"Eiconol\") was used as a dietary supplement of PUFA omega-3. The results of investigations indicated that a diet supplemented with \"Eiconol\" (8 g/day) increased the effect of dietary therapy in correction of essential hypertension and atherogenic lipids. It was not the worsening of the glycemia and activation of lipid peroxidation.", "The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. After MaxEPA treatment, there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids, while the n-6 fatty acid content decreased. The very low density lipoprotein (VLDL) triglyceride concentrations decreased significantly (by 22%) on MaxEPA treatment. However, these changes were not significantly different from those observed during the placebo period. The blood glucose concentration tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under the two regimes being significantly different (P less than 0.01). In addition, the rate constant for glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase during administration of the placebo, there being a significant difference (P less than 0.03) between the changes during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear.", "Effects of fish oil supplements on metabolic variables are insufficiently clarified in type 2 diabetes.\n We aimed to investigate short-term (1 wk) and longer-term (9 wk) effects of n-3 fatty acids.\n Twenty-six subjects with type 2 diabetes without hypertriacylglycerolemia participated in a double-blind controlled study. Median intake in the intervention group was 17.6 mL fish oil/d (1.8 g 20:5n-3, 3.0 g 22:6n-3, and 5.9 g total n-3 fatty acids). The control group received 17.8 mL corn oil/d (8.5 g 18:2n-6).\n Plasma phospholipid 20:5n-3 and 22:6n-3 increased, whereas 18:2n-6 decreased, in the fish oil group compared with the corn oil group after 1 wk. The two n-3 fatty acids also increased in adipose tissue biopsy samples taken after 9 wk in the fish oil group. Glucose concentrations (home-monitored) were approximately 1 mmol/L higher in the fish oil group than in the corn oil group at the end of the intervention (P = 0.035). Glucose utilization measured by using an isoglycemic clamp was lowered in the fish oil group compared with that in the corn oil group at the end of the intervention (P = 0.049), whereas glucagon-stimulated C-peptide tended to increase (P = 0.078). The fish oil group utilized less fat for oxidation after 1 wk, with a change to more fat and less carbohydrate oxidation after 9 wk (P = 0.040), than did the corn oil group.\n A high intake of fish oil moderately increases blood glucose and decreases insulin sensitivity in persons with type 2 diabetes without hypertriacylglycerolemia and alters carbohydrate and fat utilization in a time-dependent manner.", "A state of increased oxidative stress has been recognised in type 2 diabetes mellitus (DM). The present study was done to assess the effects of low dose omega-3 fatty acids substitution in patients with type 2 DM with special reference to oxidative stress.\n Sixty-five patients with type 2 DM of body mass index (BMI) < 27 kg/m2 and thirty age and sex matched healthy controls were evaluated for blood glucose, blood pressure and lipid profile and oxidative stress was assessed in them by measuring lipid peroxides (LP), diene conjugates (DC) and reduced glutathione (RG) in the serum. Of the 65, 40 motivated patients were randomly divided into two groups--group 1 comprising of fifteen patients prescribed a diabetic diet along with a placebo and group 2 consisting of twenty-five patients on the same diet with the addition of 0.6 g omega-3 fatty acids as one capsule Maxigard (containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) twice daily. All parameters were reassessed after six weeks.\n The levels of lipid peroxides (micromol/L), diene conjugates (OD units) and reduced glutathione (mmol GSH/L) were significantly altered indicating increased oxidative stress in the diabetics compared to the healthy controls: 4.106 +/- 0.889, 2.751 +/- 0.424, 1.344 +/- 0.316 and 1.91 +/- 0.541, 1.735 +/- 0.315, 1.919 +/- 0.310, respectively (p < 0.001 for all the three). Patients in group 1 and 2 were comparable in all respects including oxidative stress at the start of therapy. After six weeks, on comparing the mean % changes in the three parameters of oxidative stress between the two groups, it was seen that the % change was significantly higher in group 2 (Maxigard group) compared to group 1 (Placebo; 5.22 +/- 1.056 (p = 0.05), 3.28 +/- 0.608 (p = 0.01), 5.27 +/- 0.585 (p < 0.001) and 0.82 +/- 0.123, 0.18 +/- 0.017, 0.56 +/- 0.035 (p < 0.001), respectively. The patients in group 2 also exhibited significantly greater improvement in glycemic status, blood pressure and lipid profiles.\n The present study documented the existence of a state of increased oxidative stress in type 2 diabetics. Significant beneficial effects of low dose omega-3 fatty acids substitution for PUFA-6 were observed not only on oxidative stress parameters but also on blood pressure and metabolic profile.", "To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue.\n A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design.\n For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue.\n A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.", "To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation, lipid metabolism, blood rheology, and platelet reactivity.\n In a double-blind, randomized, placebo-controlled study, 24 NIDDM subjects received 1800 mg of EPA-E, 900 mg of EPA-E, or a placebo (1656 mg olive oil) daily for 8 wk.\n The EPA:arachidonic acid plasma ratio increased over an 8-wk period, then declined after a 4-wk wash-out period in the fish-oil groups in a dose-dependent way. Platelet-activating factor-induced platelet aggregation decreased from 75 +/- 7% at wk 0 to 35 +/- 21% at wk 8 in the 900-mg group (P = 0.016) and from 72 +/- 11 to 40 +/- 30% in the 1800-mg group (P = 0.039), but did not change in the placebo group. No effects on ADP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly, without concomitant rise in apolipoprotein B. Triglycerides, glycemic control, lipoprotein (a), blood and plasma viscosity, erythrocyte deformability, and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced.\n Purified EPA-E in doses of 900 and 1800 mg reduces Platelet-activating factor-induced platelet aggregation without negatively affecting glycemic control. Low-density-lipoprotein cholesterol was elevated in the 1800-mg group.", "Fish-oil supplementation decreases serum triacylglycerols but may worsen hyperglycemia in patients with non-insulin-dependent diabetes mellitus. The reason for the possible deterioration of glycemia is unclear. We examined whether inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis, glycerol gluconeogenesis, or fatty acid oxidation. Nine obese patients with non-insulin-dependent diabetes mellitus participated in a randomized double-blind crossover study in which 6 wk of n-3 fatty acid supplementation (12 g fish oil) was compared with 6 wk of corn plus olive oil. Serum triacylglycerols decreased by 30% during n-3 fatty acid supplementation. Glycerol gluconeogenesis ([U-14C]glycerol) increased by 32%. However, overall glucose production ([3-3H]glucose), glycemic control, and fatty acid oxidation remained unchanged. Thus, 6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with non-insulin-dependent diabetes mellitus without worsening glycemic control. However, n-3 fatty acid supplementation increases glycerol gluconeogenesis, which could contribute to deterioration of glycemic control during long-term treatment with high doses of fish-oil supplements.", "The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy." ]

[ "11854640", "11810088", "12118642" ]

[ "Buccal versus intravaginal misoprostol administration for cervical ripening.", "Sublingual misoprostol for the induction of labor at term.", "Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial." ]

[ "The purpose of this study was to compare the efficacy of misoprostol that is administered in the buccal pouch with the intravaginal route of administration.\n One hundred fifty-seven pregnant women with a singleton live gestation, Bishop score of <7, estimated fetal weight of <4500 g, and gestational age of >24 weeks were randomized to receive misoprostol that would be placed either in the buccal pouch or vagina every 6 hours. In the buccal group, after the first 2 doses of 200 microg, the dose was increased to 300 microg for the duration of the study (up to a total of 1600 microg). In the vaginal group, after the first 2 doses of 50 microg, the dose was increased to 100 microg for the duration of the study (up to a total of 500 microg). The primary outcome variable was the interval from the first dose to vaginal delivery. Power calculations indicated the need to enroll 71 patients in each arm of the study, which would allow for the detection of a 4-hour reduction in vaginal birth interval for buccal misoprostol.\n The hours from drug administration to vaginal delivery were similar between the buccal and vaginal groups (23.5 +/- 20.8 hours versus 21.3 +/- 13.4 hours), respectively. Thirty-five women (63%) versus 34 women (67%) delivered vaginally within 24 hours (P = not significant). The incidence of tachysystole was higher in the buccal group, 28 occurrences (38%) versus 15 occurrences (19%; P =.01).\n Buccal misoprostol is effective for cervical ripening but results in a higher incidence of tachysystole than does intravaginal administration.", "To evaluate the efficacy, safety, and patient acceptability of sublingual misoprostol compared with an equivalent dose administered orally for labor induction at term.\n One hundred women with medical or obstetric indications for induction of labor after 37 weeks of gestation and unfavorable cervices were randomized to receive 50 microg of misoprostol either orally or sublingually. The dose was repeated every 4 hours to a maximum of 5 doses if indicated. Previous cesarean delivery was a criteria for exclusion. Our primary outcome measure was the number of patients who went on to have a vaginal delivery within 24 hours of the induction. The need for oxytocin, mode of delivery, number of cesarean deliveries for fetal distress, uterine hyperstimulation rates, and neonatal outcomes were secondary outcome measures. Patient acceptability was assessed by questionnaires completed after delivery.\n Significantly more patients were delivered of infants within 24 hours (73.8% versus 45.7%; relative risk, 1.6; 95% confidence interval, 1.1 to 2.4) and the induction to delivery intervals were significantly shorter (20 hours versus 28.3 hours; mean difference, 8.3 hours; 95% confidence interval, 1.2 to 15.4) in the sublingual group compared with the oral group. There was 1 case of uterine hyperstimulation in the sublingual group. There were no significant differences in the mode of delivery, interventions for fetal distress, or neonatal outcomes in the 2 groups. The satisfaction rates were 82.5% and 85.7% in the oral and sublingual groups respectively, and 9.5% of patients thought that the sublingual tablets did not dissolve completely.\n There has been no previous report in the literature of misoprostol given sublingually for labor induction. Sublingual misoprostol seems to have better efficacy than oral misoprostol, seems to be acceptable to patients, and is an option to be considered to induce labor at term.", "To compare the efficacy and patient acceptability of 50 microg of sublingual misoprostol with 100 microg of oral misoprostol in the induction of labour at term.\n Non-blinded randomised comparative trial.\n Tertiary level UK Hospital.\n Two hundred and fifty women at term with indications for labour induction.\n Fifty micrograms of sublingual misoprostol or 100 microg of oral misoprostol was administered every four hours after random allocation, to a maximum of five doses.\n Number of patients delivering vaginally within 24 hours of the induction, mode of delivery, neonatal outcomes and patient acceptability.\n There was no significant difference in the number of women delivering vaginally within 24 hours of the induction in the sublingual group as compared with the oral group (62.8% vs 59%, RR 1.1, 95% CI 0.6-2.1), or in the mean induction to delivery time (21.8 vs 24.1 h, mean difference 2.3 h 95% CI -2.2 to +6.7). There was no difference in the uterine hyperstimulation rates (1.6% in both groups), operative delivery rates or neonatal outcomes. In the sublingual group, 92.6% found the induction acceptable with 15.8% finding the tablets with an unpleasant taste, while in the oral group it was 96.9% and 4%, respectively. More patients in the oral group thought that they would consider the same method of induction again as compared with the sublingual group (58.6% vs 40%, RR 1.4, 95% CI 1.04-1.9).\n Fifty micrograms of sublingual misoprostol every four hours has the same efficacy and safety profile as compared with 100 microg orally, but the oral route might be preferred by women." ]

[ "22473231", "16551154", "15889606", "9825167" ]

[ "Vaginismus treatment. Hypnotherapy versus behavior therapy.", "Cognitive-behavioral therapy for women with lifelong vaginismus: a randomized waiting-list controlled trial of efficacy.", "[Treatment of vaginismus with the Paula Garburg sphincter muscle exercises].", "Therapy for vaginismus: in vivo versus in vitro desensitization." ]

[ "To investigate the effectiveness of hypnotherapy in the treatment of vaginismus compared to behavior therapy.\n A consecutive sample of 36 women with vaginismus (DSM-IV criteria) referred to the out-patient psychiatry clinic at King Abdul-Aziz University Hospital in Riyadh between 1999-2003 were divided into 2 groups for either treatment on a random basis. A female psychologist independently and carefully assessed patients before and after treatment. Patients were treated until they achieved satisfactory sexual intercourse.\n Although both behavior therapy and hypnotherapy were successful in treating vaginismus, hypnotherapy performed better than behavior therapy in reducing the level of the wife`s sex-related anxiety and in improving the husband`s sexual satisfaction score. Success tended to occur faster in women treated with hypnotherapy as they received fewer treatment sessions. Women with vaginismus can be successfully treated by hypnotherapy without simultaneous treatment of their husbands.\n Hypnotherapy can provide an acceptable time and cost effective therapeutic tool that helps resolve vaginismus and improves sexual satisfaction in both spouses.", "Women with lifelong vaginismus (N=117) were randomly assigned to cognitive-behavioral group therapy, cognitive-behavioral bibliotherapy, or a waiting list. Manualized treatment comprised sexual education, relaxation exercises, gradual exposure, cognitive therapy, and sensate focus therapy. Group therapy consisted of ten 2-hr sessions with 6 to 9 participants per group. Assistance with minimal-contact bibliotherapy consisted of 6 biweekly, 15-min telephone contacts. Twenty-one percent of the participants left the study before posttreatment assessment. Intent-to-treat analysis revealed that successful intercourse at posttreatment was reported by 14% of the treated participants compared with none of the participants in the control condition. At the 12-month follow-up 21% of the group therapy participants and 15% of the bibliotherapy participants, respectively, reported successful intercourse. Cognitive-behavioral treatment of lifelong vaginismus was thus found to be efficacious, but the small effect size of the treatment warrants future efforts to improve the treatment.\n Copyright (c) 2006 APA, all rights reserved.", "To prospectively assess and compare a novel approach to the treatment of vaginismus based on Paula Garburg's sphincter muscle exercises to the traditional approach based on Masters & Johnson.\n The study population included 60 consecutive patients with vaginismus who were referred to our sex therapy clinic. The patients were randomly assigned into two groups. The study group (30 patients) underwent a step-by-step program consisting of the performance of the Paula Garburg sphincter muscle exercises to achieve pelvic muscle relaxation combined with the active introduction of Young vaginal dilators of graduated size. A control group (30 patients) underwent a behavioral treatment based on Masters and Johnson's desensitization approach that was combined with the active introduction of Young vaginal dilators of graduated size.\n All patients completed the program, all with a successful outcome, as defined by the achievement of full intercourse or the introduction of a number 6 Young vaginal dilator. The mean number of treatment sessions required for successful outcome was shorter in the study as compared to the control group (4.9 +/- 1.4 vs. 7.4 +/- 3.5, respectively. P < 0.001). Furthermore, while the percentage of patients undergoing up to 5 sessions until successful outcome was significantly higher in the study as compared to the control group (p < 0.05), the percentage of patients undergoing > 10 sessions was significantly lower.\n Paula Garburg's sphincter muscle exercises together with the use of Young vaginal dilators is a simple, easy and very effective treatment for vaginismus. The outcome matched or even surpassed that of the traditional behavioral approaches.", "To verify the effectiveness of desensitization exercises with dilators in the treatment of vaginismus, while comparing 2 therapeutic variations with differing instruction procedures (\"in vivo\" versus \"in vitro\") during the desensitization exercises.\n A consecutive random sample of 44 female outpatients in sexual therapy were divided into groups for either treatment on a random basis. All patients were treated until the symptoms abated on the basis of a structured therapy program. The stability of the therapeutic success was verified through follow-up interviews.\n Forty-three (97.2%) of the patients were able to have sexual intercourse after an average of 6.3 therapeutic sessions. One-third reported an increase in their sexual desire. Thirty-four of 39 patients (87.2%) would be prepared to repeat the therapy. There were no significant differences in the success and the required number of consultations for the cure between the 2 groups investigated.\n Desensitization through exercises with dilators is an effective method for treating vaginismus. The choice of instruction procedure can be left to the patient." ]

[ "3318993", "8173852", "13588962", "12972485", "10568861", "7551664" ]

[ "Intra-articular rimexolone in the rheumatoid knee: a placebo-controlled, double-blind, multicentre trial of three doses.", "A randomized controlled study of post-injection rest following intra-articular steroid therapy for knee synovitis.", "Intra-articular therapy in rheumatoid arthritis: comparison of hydrocortisone tertiary butyl acetate and hydrocortisone acetate.", "Randomised controlled study of postinjection immobilisation after intra-articular glucocorticoid treatment for wrist synovitis.", "Intraarticular morphine versus dexamethasone in chronic arthritis.", "The effects of joint washout and steroid injection compared with either joint washout or steroid injection alone in rheumatoid knee effusion." ]

[ "One-hundred and thirty-seven patients with classical or definite rheumatoid arthritis, involving at least one knee joint, were randomly allocated to a single intra-articular injection of 10, 20 or 40 mg of rimexolone (Org 6216) or placebo. The follow-up period was 84 days, during which clinical and laboratory assessments were done. Clinical improvement of the treated knee joint was measured by the following variables: pain, tenderness, morning stiffness, swelling, range of movement and walking ability. Placebo response was considerable. However, clinical improvement with rimexolone at 20 mg and 40 mg was significantly superior to placebo for most of the variables, whilst with the 10 mg dose only reduction of tenderness was significantly superior. The duration of improvement was longest with 40 mg of rimexolone. One single, intra-articular injection of this dose into the affected knee joint provided significant reduction in pain, tenderness and stiffness and improved the range of movement and walking ability for a period of 8 to 12 weeks.", "In order to assess the effect of 24 h observed bed rest following intra-articular steroid injection of the knee joint in patients with an inflammatory arthritis such as RA, AS or colitic arthropathy, 91 patients with inflammatory arthritis of one knee joint were randomized to receive 24 h bed rest in hospital following intra-articular steroid injection or were injected in outpatients. The clinical and laboratory assessments such as pain and stiffness on a 10-cm visual analogue scale, knee circumference (cm), 50 ft walking time (s), CRP and ESR were measured before receiving the steroid injection and at 3, 6, 12 and 24 weeks. Both groups of patients improved clinically and serologically at 3 weeks. By 12 weeks the degree of improvement in the pain score, stiffness score, knee circumference, 50 ft walking time and CRP was better in the rest group and these differences persisted to 24 weeks. For each outcome variable the summary measure of response was significantly better in the rest group compared to the no rest group. Intra-articular steroid injection of the knee joint followed by strict i inpatient bed rest for 24 h results in a greater degree of clinical and serological improvement, compared to routine outpatient injections for up to 6 months. It is therefore possible that 24-h post-injection rest will result in a prolonged duration of clinical response and reduce the need for frequent steroid injections and the risk of complications.", "nan", "Intra-articular glucocorticoid treatment is frequently used in arthritic disorders. Postinjection rest has been shown to improve the outcome of knee injections.\n To investigate whether better treatment results might also be achieved by a similar postinjection regimen for the wrist, which is non-weightbearing.\n 117 patients with rheumatoid arthritis and wrist synovitis were treated with intra-articular glucocorticoid injections. The patients were randomly allocated to 48 hour postinjection immobilisation in elastic wrist orthoses (n=58) or to normal postinjection activity (n=59). The primary end point was relapse of synovitis. In addition, joint circumference, pain, function, range of movement, and grip strength were followed up during six months.\n 24 relapses occurred in the orthoses group and 14 in the active group (p=0.056). The secondary measure showed no statistically significant differences between the groups.\n The use of elastic wrist orthoses as a postinjection regimen does not improve the outcome of intra-articular glucocorticoid treatment for wrist synovitis. Results achieved in studies on knees should not be generalised to other joints, and postinjection recommendations should differ depending on the joint treated.", "Intraarticular morphine inhibits pain after knee surgery without overt toxicity. This study examined intraarticular morphine in chronic arthritis. We undertook a randomized double-blind comparison between intraarticular morphine (3 mg), dexamethasone (4 mg) and saline (3 ml) in 44 patients with chronic inflammatory arthritis or osteoarthritis of the knee. Pain (the primary outcome measure) was assessed at rest and during activity for 6 days using a visual analog scale (VAS) and the McGill pain questionnaire. Before drug injections and on day 6 synovial leukocyte counts (the secondary outcome measure) were taken. During the first 6 h after injection both morphine and dexamethasone significantly reduced VAS and pain rating indices (PRI) in comparison to saline. Both substances also produced a significant reduction of PRI compared to saline during the subsequent 5 days. No patient displayed untoward side effects. Synovial leukocyte counts were lower after morphine than after saline. In conclusion, intraarticular morphine produces analgesia of similar magnitude to dexamethasone and it may have antiinflammatory actions in chronic arthritis.", "Patients with rheumatoid arthritis attending rheumatology out-patients who had a symptomatic knee effusion were randomly allocated to receive one of three treatments: group I, a steroid injection without washout; group II, a joint washout with normal saline; group III, a joint washout with normal saline and steroid injection. Sixty knees in all were studied. Laboratory parameters for disease activity (erythrocyte sedimentation rate, C-reactive protein) were monitored in all patients prior to the study and at 3 months. Clinical assessment of disease activity (pain, morning stiffness involving the knee, circumference of the knee, walking distance and range of movement) were recorded prior to the study, at 1 month and at 3 months. All three treatments, resulted in a reduction of pain and increased movement. However, patients who had a joint washout alone showed significantly less improvement as compared with the other two groups. Symptomatic improvement was marginally greater in patients following joint washout and injection than in those who had had joint injection alone. The results of the study indicate that the simple procedure of joint aspiration and steroid injection, which can be carried out in the out-patient clinic, provides satisfactory relief of symptoms in rheumatoid patients with knee effusions. Joint washout alone was less beneficial." ]

[ "16818837", "18814887", "17079787", "12897288" ]

[ "Accuracy and impact of a point-of-care rapid influenza test in young children with respiratory illnesses.", "A randomized, controlled trial of the impact of early and rapid diagnosis of viral infections in children brought to an emergency department with febrile respiratory tract illnesses.", "Effect of point-of-care influenza testing on management of febrile children.", "Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial." ]

[ "To determine whether a point-of-care rapid influenza test impacts the diagnostic evaluation and treatment of children with acute respiratory illnesses.\n Randomized controlled trial.\n Pediatric emergency department and acute care clinic of a children's hospital.\n Children aged younger than 5 years with fever or acute respiratory symptoms during 2 influenza seasons (2002 through 2004).\n Surveillance days were randomized to performance or no performance of a point-of-care rapid influenza test. All children had a nasal and throat swab obtained for laboratory tests. The rapid test group had another nasal swab obtained for the QuickVue Influenza Test (Quidel Corp, San Diego, Calif), which was performed by nurses; results were shared immediately with treating physicians.\n Rapid test results were compared with results of the viral culture or 2 polymerase chain reaction assays for influenza. Diagnostic test ordering and antibiotic prescribing were compared for the groups.\n Of 468 enrolled children, 306 were from the emergency department and 162 from the clinic. Overall, 88 children (19%) had influenza infection. Of 205 children in the rapid test group, 51 (25%) had influenza infection. The rapid influenza test was 82% sensitive and 99% specific. In the emergency department, fewer children in the rapid test group had diagnostic tests ordered than in the no rapid test group (39% vs 51%, P = .03). There was no difference in test ordering in the clinic or in antibiotic prescribing in either setting. The use of antivirals was low.\n Point-of-care rapid influenza tests were sensitive and specific and were associated with less diagnostic testing in the emergency department.", "Acute respiratory tract infections represent a significant burden on pediatric emergency departments (ED) and families. We hypothesized that early and rapid diagnosis of a viral infection alleviates the need for ancillary testing and antibiotic treatment.\n We conducted a randomized, controlled trial of children 3 to 36 months of age with febrile acute respiratory tract infections at a pediatric ED. Two hundred four subjects were randomly assigned to receive rapid respiratory viral testing on admission or a routine ED admission protocol. Outcome measures were: mean length of visits, rate of ancillary tests, and antibiotic prescription in the ED. A follow-up call was made to all study subjects to inquire about further healthcare visits, ancillary testing, and antibiotic prescription after ED discharge.\n We did not find a statistically significant difference in ED length of visits, rate of ancillary testing, or antibiotic prescription rate in the ED between the study groups. There was, however, a significant reduction in antibiotic prescription after ED discharge (in the group who had rapid viral testing RR = 0.36; 95% CI = 0.14, 0.95).\n Rapid multi-viral testing in the ED did not significantly affect ED patient treatment but may reduce antibiotic prescription in the community after discharge from the ED, suggesting a novel strategy to alter community physician antibiotic prescription patterns.", "To determine the effect of point-of-care testing (POCT) for influenza on the physician management of febrile children who are at risk for serious bacterial illness (SBI) on the basis of age and temperature and who are presenting to a pediatric emergency department (ED) during an influenza outbreak.\n Patients 2-3 months of age with temperature of > or = 38 degrees C and patients 3-24 months of age with temperature of > or = 39 degrees C who were presenting to a pediatric ED during an influenza outbreak were enrolled into a prospective, quasi-randomized, controlled trial. Influenza testing was performed on enrolled patients by either the POCT or the standard-testing (ST) methods. The two groups were compared in terms of laboratory testing, chest radiography, antibiotic use, visit-associated costs, pediatric ED lengths of stay, inpatient admission, and return visits to the pediatric ED. Similar analyses also were performed on the resulting subgroups of patients on the basis of method of testing (POCT or ST) and test result (positive or negative).\n Of 767 eligible patients, 700 (91%) completed the study. No significant differences were demonstrated between the POCT and ST groups with respect to laboratory tests ordered, chest radiographs obtained, antibiotic administration, inpatient admission, return visits to the pediatric ED, lengths of stay, or visit-associated costs. In the subgroup analysis, the adjusted odds ratios (ORs) for blood culture in influenza test-positive to -negative patients were 0.59 and 0.71 in the POCT and ST groups, respectively (p = 0.088). The adjusted ORs for urine culture in influenza test-positive to -negative patients were 0.46 and 0.67 in the POCT and ST groups, respectively (p = 0.005).\n When using a strategy of performing influenza testing on all patients at risk for SBI who presented to a pediatric ED during an influenza outbreak, the method of testing (POCT or ST) did not appear to significantly alter physician management, cost, or length of stay in the pediatric ED. However, if the interaction of the method of testing and the test result (positive or negative) were considered, a positive POCT for influenza was associated with a significant reduction in orders for urinalyses and urine cultures.", "To determine the impact of the rapid diagnosis of influenza on physician decision-making and patient management, including laboratory tests and radiographs ordered, patient charges associated with these tests, antibiotics/antivirals prescribed, and length of time to patient discharge from the emergency department.\n Patients aged 2 months to 21 years presenting to an urban children's teaching hospital emergency department were screened for fever and cough, coryza, myalgias, headache, and/or malaise. After obtaining informed consent, patients were randomized to 1 of 2 groups: 1) physician receives (physician aware of) the rapid influenza test result; or 2) physician does not receive (physician unaware of) the result. For patients in the physician aware group, nasopharyngeal swabs were obtained, immediately tested with the FluOIA test for influenza A and B, and the result was placed on the chart before patient evaluation by the attending physician. For the physician unaware group, nasopharyngeal swabs were obtained, stored according to manufacturer's directions, and tested within 24 hours. Results for the physician unaware group were not disclosed to the treating physicians at any time. The 2 resultant influenza-positive groups (aware and unaware) were compared for laboratory and radiograph studies and their associated patient charges, antibiotic/antiviral prescriptions, and length of stay in the emergency department.\n A total of 418 patients were enrolled, and 391 completed the study. Of these, 202 tested positive for influenza. Comparison of the 96 influenza-positive patients whose physician was aware of the result with the 106 influenza-positive patients whose physician was unaware of the result revealed significant reductions among the former group in: 1) numbers of complete blood counts, blood cultures, urinalyses, urine cultures, and chest radiographs performed; 2) charges associated with these tests; 3) antibiotics prescribed; and 4) length of stay in the emergency department. The number of influenza-positive patients who received prescriptions for antiviral drugs was significantly higher among those whose physician was aware of the result.\n Physician awareness of a rapid diagnosis of influenza in the pediatric emergency department significantly reduced the number of laboratory tests and radiographs ordered and their associated charges, decreased antibiotic use, increased antiviral use, and decreased length of time to discharge." ]

[ "10665553", "6755786", "1788755", "1402213", "6474351", "7934346", "3555690", "9392698", "1987387", "6465619" ]

[ "Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial.", "Effects of aspirin and dipyridamole on expanded polytetrafluoroethylene graft patency.", "[Experiences with adjuvant prostaglandin therapy in vascular surgery interventions].", "Indobufen vs acetylsalicylic acid plus dipyridamole in long-term patency after femoropopliteal bypass.", "Effect of aspirin and dipyridamole on the patency of lower extremity bypass grafts.", "Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting.", "Random control trial of a short course of aspirin and dipyridamole (Persantin) for femorodistal grafts.", "Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs. Etude de la Ticlopidine après Pontage Fémoro-Poplité and the Association Universitaire de Recherche en Chirurgie.", "Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.", "Prevention of post-operative thrombosis in peripheral arteriopathies. Pentoxifylline vs. conventional antiaggregants: a six-month randomized follow-up study." ]

[ "Oral anticoagulants and aspirin are antithrombotic drugs that are commonly used in patients with vascular disease. We investigated whether either of these treatments prevented more effectively than the other bypass complications after infrainguinal bypass surgery.\n We did a multicentre, randomised, open trial. 2690 patients who had undergone infrainguinal grafting were randomly assigned oral anticoagulants (target international normalised ratio 3.0-4.5, n=1339) or aspirin (80 mg daily, n=1351). We followed up patients for a mean of 21 months. The primary outcome was graft occlusion.\n 308 graft occlusions occurred in the oral-anticoagulants group compared with 322 in the aspirin group (hazard ratio 0.95 [95% CI 0.82-1.11]), which suggested no overall advantage for either treatment. Oral anticoagulants were beneficial in patients with vein grafts (0.69 [0.54-0.88]), whereas aspirin had better results for nonvenous grafts (1.26 [1.03-1.55]). The composite outcome of vascular death, myocardial infarction, stroke, or amputation occurred 248 times in the oral-anticoagulants group and 275 times in the aspirin group (0.89 [0.75-1.06]). Patients treated with oral anticoagulants had more major bleeding episodes than those treated with aspirin (108 vs 56; 1.96 [1.42-2.71]).\n Oral anticoagulation was better for the prevention of infrainguinal-vein-graft occlusion and for lowering the rate of ischaemic events. Aspirin was better for the prevention of non-venous graft occlusion, and was associated with fewer bleeding episodes.", "A randomized, double-blind clinical trial was designed to assess the effect of aspirin (ASA) alone or in combination with dipyridamole (DIP) on the patency rates of expanded PTFE grafts placed in the infrainguinal position. Forty-nine patients were randomized into three groups who received three times daily either two placebos (17 patients), 325 mg ASA and placebo (16 patients), or 325 mg ASA and 75 mg DIP (16 patients). The patients were seen at 3-month intervals for 1 year, and coded medication bottles were dispensed and returned pills counted to assess patient compliance. Treatment failure was defined as the first graft occlusion. The data were analyzed using the Breslow statistic for progressively censored survival type data. The 1-year cumulative patency rate for the entire series was 59%. The rates for above-knee grafts in the ASA group (100%) and the ASA/DIP group (100%) were significantly higher than the rates for the placebo group (50%) (P = 0.05). The 1-year cumulative patency rates for patients with below-knee grafts were not statistically different among the groups, although the patients who received ASA alone had a higher rate than did the other two groups (65% versus 21% for placebo and 19% for ASA/DIP). There were fewer occlusions in the above-knee grafts as compared to below-knee grafts in all groups, but the differences were statistically significant only in the ASA/DIP group. There were no statistical differences between the two active treatment groups.", "Two prospective randomized trials were referred. In the first study 50 patients with femorotibial greater saphenous vein in situ bypasses were treated intraarterially with 0.2 ng PGE 1/kg body weight/min and 15,000 i.U. of heparine continuously. The control group of 50 patients also got 15,000 i.U. of heparine and 3 x 0.5 g of Aspirin. We observed 2 (4%) immediate occlusions in the PGE 1 group and 7 (14%) immediate occlusions in the control group. This difference proved to be statistically significant. In the second study 83 patients with three level occlusions (ilio-femoro-tibial) in stage III and IV were treated with a profundaplasty. 42 patients received 60 micrograms PGE 1 in 250 ml saline twice daily. The control group of 41 patients only got twice 250 ml saline over a period of three weeks. In the PGE 1 group 26 patients (61%) showed disappearance of rest pain and healing of necrotic lesions, whereas in the control group this could only be achieved in 15 patients (35%). The difference proved to be statistically significant.", "To compare the effects of indobufen (INB) with those of ASA+dipyridamole (DP) on graft patency, 113 patients undergoing femoropopliteal bypass surgery were randomly and blindly assigned to treatment with INB 400 mg daily or with ASA 900 mg daily plus DP 225 mg daily. Treatment started 2 days before surgery and lasted for 12 months. All patients underwent two angiographic examinations: the first early after surgery (mean 6 days) and the second at the end of the study (mean 368 days). The 1 year cumulative patency rate for INB was 60% higher but not statistically different from the ASA-DP group (53.2%). The relative risk (INB/ASA+DP) calculated by the Mantel-Haenszel test was 0.86 (confidence limits 0.54-1.35). Only the site of operation (above-knee or below-knee) has a significant prognostic value on the fate of the graft.", "Recent clinical studies indicate that the use of aspirin and dipyridamole improves graft patency rates in patients with infrainguinal polytetrafluoroethylene (PTFE) grafts and aortocoronary vein grafts. We undertook a prospective, double-blind, randomized study to determine whether these drugs administered postoperatively to patients with PTFE or autologous vein infrainguinal bypasses would improve graft patency during the first 24 months after operation. Patients received either aspirin 325 mg and dipyridamole 75 mg or identical placebo tablets three times a day, taken orally. Patency rates were compared by computing standard life tables and comparing cumulative patency rates. One hundred patients with 102 grafts were studied. The cumulative patency rate at 24 months was not significantly different for the treatment (57%) versus control (67%) groups or for any subgroup. We conclude that aspirin and dipyridamole administered postoperatively in the doses used in this study do not improve the overall patency rates of vein or PTFE infrainguinal bypass grafts.", "Low-molecular weight heparin has theoretical advantages over aspirin and dipyridamole in maintaining vascular-graft patency by virtue of its better antithrombotic effect and antiproliferative activity on vascular, smooth-muscle cells. We tested the hypothesis that low-molecular weight heparin would be more effective than aspirin and dipyridamole in maintaining graft patency in patients undergoing femoropopliteal bypass grafting. Patients were randomised to receive either a daily injection of 2500 IU low-molecular weight heparin, or 300 mg aspirin with 100 mg dipyridamole 8 hourly for 3 months. 94 patients were randomised to low-molecular weight heparin and 106 to aspirin and dipyridamole. Patients were stratified according to indication for surgery and were followed up for 1 year. Kaplan-Meier estimate of graft patency showed 87% graft survival on low-molecular-weight heparin and 72% on aspirin and dipyridamole at 6 months. At 12 months, the respective figures were 78% and 64%. Stratified survival analysis showed that this benefit was confined to those having salvage surgery (log rank test p = 0.0006); for those having surgery for claudication there was no significant benefit. No major bleeding events occurred in either group. We conclude that low-molecular weight heparin is better than aspirin and dipyridamole in maintaining femoropopliteal-graft patency in patients with critical limb ischaemia undergoing salvage surgery. This treatment should have considerable cost benefits.", "The effect of a short course of anti-platelet agents, started preoperatively, on the patency of femorodistal bypass grafts is unknown. One hundred and forty-eight such grafts were randomized to act as controls or to receive dipyridamole 200 mg b.d. for 48 h pre-operatively and dipyridamole 200 mg b.d. with aspirin 300 mg daily for 6 weeks after surgery. Patients were well-matched and the mean pre-operative pressure index of 0.37 rose to 0.78 during the first postoperative week. No deaths were attributable to the treatment. Ninety-three grafts were autogenous vein and the remainder were prosthetic (GORE-TEX (PTFE), human umbilical vein or externally supported Dacron). At 1 year autogenous vein cumulative patency was 75 per cent. Overall results showed higher patency in the treated group (P = 0.012) which was entirely accounted for by the difference between prosthetic dipyridamole and aspirin group (85 per cent patency) and prosthetic control groups (53 per cent patency, P = 0.005) and arose during the first postoperative month. There were 11 deaths and 8 amputations in the dipyridamole and aspirin group and 8 deaths and 12 amputations in the control group. It is concluded that a six week perioperative course of dipyridamole and aspirin allows the patency of prosthetic femorodistal bypass to approach that of autogenous vein, and the regimen therefore is recommended for patients who may require a prosthetic graft.", "Optimal therapy to prevent late occlusion of arterial bypass grafts in the legs has not been determined. We assessed the effect of ticlopidine, an inhibitor of platelet aggregation, on the long-term patency of saphenous-vein bypass grafts for the treatment of peripheral vascular disease.\n A total of 243 patients with femoropopliteal or femorotibial saphenous-vein bypass grafts were randomly assigned to receive either ticlopidine (250 mg twice a day) or matching placebo for two years. The primary end point was graft patency at two years, as assessed by physical examination, measurement of the ankle brachial index, and duplex ultrasonography or arteriography. The incidence of death and major ischemic events was also analyzed in the two groups.\n After two years, 66.4 percent of the patients were alive with a patent graft in the ticlopidine group, as compared with 51.2 percent in the placebo group (95 percent confidence interval for the difference between the two groups, 2.9 to 27.4 percent; P=0.02). The two-year cumulative patency rate was 82 percent in the ticlopidine group and 63 percent in the placebo group (P=0.002). There was no significant difference between groups in overall mortality or major ischemic events.\n Ticlopidine significantly improved the long-term patency of saphenous-vein bypass grafts in the legs. Since the drug was well tolerated, its use can be recommended after peripheral-vein bypass surgery.", "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.", "The patency rate and reocclusion incidence were studied in 97 patients following vascular surgery necessitated by occlusion in the aortoiliac or femoropopliteal regions or both. Forty-nine patients were treated orally with a combination of acetylsalicylic acid and dipyridamole (1050 mg + 150 mg/day) and 48 patients with the haemorheologically active agent pentoxifylline (1200 mg/day, Trental 400 tds.) for uniform periods of 6 months. Reocclusion occurred in 10 patients receiving ASAD and in 5 patients receiving pentoxifylline. Adverse reactions were recorded in 12 patients with ASAD (discontinuation in 11) and in 3 patients with pentoxifylline (discontinuation in 2). Patency and tolerability rate were significantly superior in those patients treated with pentoxifylline, suggesting that the combination of haemorheological effects with antihaemostaseological and antithrombotic properties offered by pentoxifylline may be of benefit in the prevention of reocclusion after vascular surgery." ]

[ "463541" ]

[ "Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position." ]

[ "Seventy-one sick newborn infants, who had an umbilical artery catheterized, were randomized in one of four catheter groups: long end-hole-, short end-hole-, long side-hole- or short side-hole catheter. A long catheter means a high position of the catheter tip (Th6--11) and a short catheter a low position of the tip (L3--5). An angiography through the indwelling catheter in order to diagnose thrombosis was performed before the catheter was withdrawn. Dissection of the aorta and its brances was performed on infants who died. The total frequency of thromboses was 26%. There were no thromboses among infants with long end-hole catheters while infants with short end-hole catheters had thrombosis in 26%, long side-hole catheters in 33% and short side-hole catheters in 64%. Long end-hole catheters functioned better than the others. Only 6 of 16 infants with thrombosis had physical signs from the legs, while 12 infants without thrombosis had similar signs." ]

[ "8251778", "8257235", "8721977", "8995350", "9929524", "2690762", "10197321", "8897354", "3278764", "1963364", "8377779" ]

[ "Treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone (coumarin).", "Reduction of filaritic lymphoedema and elephantiasis by 5,6 benzo-alpha-pyrone (coumarin), and the effects of diethylcarbamazine (DEC).", "Treatment of secondary lymphedema of the upper limb with CYCLO 3 FORT.", "Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer).", "Lack of effect of coumarin in women with lymphedema after treatment for breast cancer.", "The effects of 5,6 benzo-[a]-pyrone (coumarin) and DEC on filaritic lymphoedema and elephantiasis in India. Preliminary results.", "Comparative study of the clinical efficacy of two different coumarin dosages in the management of arm lymphedema after treatment for breast cancer.", "The use of 5,6 benzo-[alpha]-pyrone (coumarin) and heating by microwaves in the treatment of chronic lymphedema of the legs.", "A double-blind, cross-over trial of O-(beta-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs.", "[Benzo-pyrones in the treatment of chronic lymphoedema of the arms and legs].", "Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone." ]

[ "To study efficacy of treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone.\n Randomised, double blind, placebo controlled study with matching for grade and duration of disease, age, and sex. Treatment was given for 367 days, and subjects were followed up for another year.\n A town in Shandong Province, China.\n 104 men and women with chronic unilateral filarial lymphoedema or elephantiasis of the leg: 64 were randomised to benzopyrone and 40 to placebo. By the end of the study 19 patients had dropped out of the treatment group and two out of the placebo group.\n Two 200 mg tablets of 5,6-benzo-alpha-pyrone or two placebo tablets given daily.\n Volumes of the affected and normal legs estimated every three months, and daily listing of any side effects.\n Benzopyrone reduced oedema for all grades of lymphoedema during the year of treatment (pW0.001) and the follow up year (p = 0.026). During treatment the mean monthly reductions in leg volume were 0.62% (95% confidence intervals 0.4% to 0.85%), 1.1% (0.71% to 1.6%), and 1.6% (0.89% to 2.3%) of the volume of the normal leg for grades 1, 2, and 3-5 (elephantiasis) of lymphoedema respectively. During follow up the mean monthly reductions were 0.18% (0.01% to 0.35%), 0.54% (0.27% to 0.82%), and 0.87% (0.51% to 1.2%). At the end of the trial the total reduction in oedema was 100%, 95%, and 45% for grades 1, 2, and 3-5. Symptoms and complications were considerably reduced, including attacks of secondary acute inflammation, while side effects were minor and disappeared after one month. In the placebo group there were no changes in the severity of lymphoedema.\n 5,6-benzo-alpha-pyrone reduces the oedema and many symptoms of filarial lymphoedema and elephantiasis. It has few side effects, and its relatively slow action makes it ideal for use without compression garments.", "Chronic filaritic lymphoedema and elephantiasis, in India, were treated orally with 5,6 benzo-alpha-pyrone (56 BaP; 1,2 benzo-alpha-pyrone; coumarin) in a double-blind, randomized, matched-group trial. Each group finally contained 40-55 patients. Patients were observed for about 2 years (ranging from 6 to 45 months, with 75% completing the 2 years). The 56 BaP slowly, but very significantly (P < 0.0001), reduced all grades of lymphoedema and elephantiasis. Two thirds of the oedema was lost by grade 2 over 2 years. Grades 3 to 5 were reduced by a fifty over that time. The greater the initial oedema, the greater was its rate of resolution. A slowly worsening condition thus became a slowly improving one. Slowness has its advantages: compression stockings, that are impractical in hot, wet or dirty conditions, are not necessary. The slowly remodelling fibrous tissue, while lessening in amount, is still able to hold the tissues together. The 56 BaP considerably improved many symptoms and complications, particularly bursting-pains, inflammation and ulcers. It is cheap and of very low toxicity. Diethylcarbamazine (DEC) was studied with and without 56 BaP. DEC alone gave some reduction of the oedema, but this was much smaller than that with 56 BaP. It considerably worsened the reductions by 56 BaP, while 56 Bap slightly improved those by DEC and reduced the fever caused by DEC. Together, they reduced feelings of swelling and bursting-pain, fungal infections, lymphangitis and lymphadenitis more than when used alone.", "Fifty seven patients with secondary lymphedema of the upper limb after previous treatment for breast cancer were treated for 3 months with an extract of Ruscus + Hesperidin Methyl Chalcone (CYCLO 3 FORT) or placebo according to a double-blind protocol in the context of a controlled clinical trial. All patients also underwent manual lymphatic drainage twice a week for at least one month. With CYCLO 3 FORT, the reduction in volume of arm edema, the main assessment criteria, was 12.9% after 3 months of treatment as compared with a placebo (p=0.009). Decreased edema tended to be more marked in the forearm compared with the upper arm where excess fat deposition seemed to dominate over excess fluid accumulation. CYCLO 3 FORT was well tolerated with minimal adverse reaction.", "To assess the activity of a purified, micronized, flavonoidic fraction (Dios; Daflon 500 mg*) on upper limb lymphedema occurring after breast cancer therapy, a monocenter, randomized, double-blind, parallel group vs placebo (Plac) trial was carried out. One hundred and four women with lymphedema were included; 94 completed the study (46 Dios, 48 Plac). A subset of 24 patients with more severe lymphedema (10 Dios, 14 Plac) was subjected to a separate analysis. Treatment consisting of Dios or Plac was given two tablets daily over a six-month period. A radionuclide lymphoscintigraphy using technetium-99m was performed at inclusion and at the end of the treatment. The upper limb volume was measured every two months. In the overall population the evolution of parameters was not different between Dios and Plac. In the 24 patients with a more severe lymphedema, the lymphoscintigraphic parameters (m +/- sd) were as follows: lymphatic migration speed was significantly improved by Dios in comparison with Plac (delta Speed cm/minute: 0.84 +/- 0.6 vs 0.14 +/- 0.26, P = 0.005). The half-life of the colloidal compound was significantly improved over time in the Dios group (delta half-life = 10.3 +/- 13.07 minute, P = 0.034) but not in the Plac group (delta half-life = 0.53 +/- 15.51 minute, P = 0.086). The change over time of colloidal clearance was close to significance in the Dios group (delta clearance microL/minute: 2.18 +/- 3.10, P = 0.054) but not in the Plac group (0.11 +/- 2.26, P = 0.86). No significant difference was found for evolution of lymphedema volume, despite a tendency in favor of Dios. This can be related to wide distribution of volume values and small numbers of patients. In conclusion, these results suggest a beneficial therapeutic activity of Dios at the usual dose of two tablets/day in patients affected with more severe lymphedema. The clear improvement of the lymphatic speed illustrates its known lymphokinetic activity. Further studies with a higher dosage could confirm the beneficial activity of this drug in secondary lymphedema.", "Lymphedema of the arms can be a serious consequence of local and regional therapy in women with breast cancer. Coumarin has been reported to be effective for the treatment of women with lymphedema; we undertook a study in which we attempted to replicate those findings.\n We studied 140 women with chronic lymphedema of the ipsilateral arm after treatment for breast cancer. The women received 200 mg of oral coumarin or placebo twice daily for six months and then the other treatment for the following six months. The end points of the study consisted of the volume of the arm (calculated from measurements of hand and arm circumference) and the answers on a questionnaire completed by the patient about symptoms potentially related to lymphedema.\n The volumes of the arms at 6 and 12 months, were virtually identical, regardless of whether coumarin or placebo was given first. After six months, the average volume of the affected arm increased by 21 ml during placebo treatment and 58 ml during coumarin treatment (P=0.80). In addition, answers to patient-completed questionnaires were similar in the two treatment groups. After six months only 15 percent of the women in the coumarin group and 10 percent of those in the placebo group reported that the study medication had helped a moderate or large amount (P=0.19). Coumarin was well tolerated, except that it resulted in serologic evidence of liver toxicity in 6 percent of the women.\n Coumarin is not effective therapy for women who have lymphedema of the arm after treatment for breast cancer.", "A randomized double-blind, placebo-controlled, trial of 5,6 benzo-[alpha]-pyrone (coumarin, '56 BaP') and of diethylcarbamazine (DEC) is being performed on patients with filaritic lymphoedema and elephantiasis over two years, using matched groups. In 169 patients there were significant (1% level) reductions in the amounts of oedema for the patients taking 56 BaP. The excess limb volumes were reduced from 40 to 25% over two years. A similar, but less significant (5% level), improvement was found for the circumference measurements. The rate of reduction was increased when the initial amount of oedema was greater. This therapy, while much slower than many other methods of treatment, does convert a slowly worsening condition into a slowly improving one. There were no significant reductions in the amount of oedema following DEC treatment.", "In a randomized, double-blind, parallel group study, we compared the clinical efficacy of coumarin 90 mg/day (Group A) with 135 mg/day (Group B) in 77 women (age 35-65 years) with lymphedema of the upper limb secondary to surgery and irradiation for treatment of breast cancer. During 12 months of coumarin therapy, the arm volume of lymphedema and a clinical score (degree of arm edema, heaviness, hardness, and neuralgia/dysesthesia) were determined. In both groups, the volume of arm lymphedema decreased (14.9% in Group A and 13.2% in Group B) (N.S.), the overall clinical score improved (12.9 +/- 4.3 to 5.7 +/- 3.5 in Group A and from 11.7 +/- 3.7 to 4.7 +/- 3.9 in Group B) (N.S.), and the overall efficacy of coumarin was similarly good or excellent (71.9% in Group A and 68.6% in Group B) (N.S.). Only mild to moderate side effects of drug therapy were recorded. Coumarin prevents a spontaneous trend toward an increase in arm lymphedema after treatment of breast cancer, decreases the severity of local symptoms, and overall improves the quality of life. No difference was found between the apparent benefits of coumarin at 90 mg/day compared with 135 mg/day.", "Sixty patients with leg lymphedema from a variety of etiologies were divided into randomized two groups, matched by Grade, duration, age, sex, and cause of lymphedema. Using a double-blind format, one group received 5,6 benzo-[alpha]-pyrone (coumarin 1,2 benzopyrone, 400 mg/day) for six months; the other received a placebo. For the next six months, both groups received a standardized regimen of heat (using microwaves) coupled with compression garments. Benzopyrone produced approximately 20% reduction in the volume (p = 10(-4)) and improvement in circumferences and tonometry (p = 10(-5) and 10(-7)). Symptoms (feelings of swelling, pain, heaviness and loss of mobility) were also significantly improved (p = 0.03 to 10(-7)). During the second six months, when microwave heat therapy was added to drug therapy, the patients who had previously received the placebo showed significant improvement (p = 0.03 to 10(-9)) in signs and symptoms of lymphedema. Some, but not all, of the group that was receiving benzopyrones were also significantly improved by heat therapy (p = 0.8 to 0.002). Taking benzopyrones for 12 months plus heat treatment for six months was significantly better, for some criteria, than the placebo plus heat therapy (p = 0.7 to 0.04). On the other hand, heat plus either placebo or benzopyrone was often significantly better than either the active or inactive drug without heat (p = 0.8 to 10(-9)).", "A randomised, double-blind, cross-over trial was performed on 26 patients with postmastectomy lymphoedema of the arm, and 14 with lymphoedema of the leg. For 6 months, patients took 0-(beta-hydroxyethyl)-rutosides (oxerutin; \"Paroven\", \"Venoruton\", Zyma) in doses of 3 g/day, or the placebos; then they took the reverse. Measurements (volume, circumferences, tonometry and skin temperature) were made monthly. The active drug reduced the volumes of the limbs (p less than 0.05 to 0.01) and their circumferences (p less than 0.05 to 0.001). It increased the softness of the limbs, as shown by the increases in the tonometry values (p less than 0.01 to 0.001). There was a lowering of the elevated skin temperatures (p less than 0.05 to 0.001). Patients reported increased comfort and freedom of movement, a lessening of their bursting pains, heaviness and tension (p less than 0.05 to 0.01), and an increased mobility of their limbs (p less than 0.0001). Most patients (70%) preferred the active drug (p less than 0.0001). An increase in general well-being was reported by 97% of patients when taking the active drug compared with 4% for placebo (p less than 0.0001).", "nan", "Benzopyrones can reduce the volume of high-protein edema fluid by stimulating proteolysis. These compounds provide a method for removing excess protein and its consequent edema and reduce its clinical sequelae, such as chronic inflammation and secondary infections.\n We conducted a randomized, double-blind, placebo-controlled, crossover trial of 5,6-benzo-[alpha]-pyrone in 31 patients with postmastectomy lymphedema of the arm and 21 patients with lymphedema of the leg of various causes (this agent, also known as 56 BaP, 1,2-benzopyrone, or coumarin, is not an anticoagulant). The patients received 400 mg of the active drug or placebo, each for six months.\n During the placebo period, lymphedema often worsened, especially in the arms. Measurements of limb volume showed that the active drug reduced the mean amount of edema fluid in the arms from 46 percent above normal to 26 percent above normal (P < 0.001) and the amount in the legs from 25 percent to 17 percent above normal (P < 0.001). The circumference of the arms was reduced from 17 percent to 13 percent above normal, and the circumference of the legs from 11 percent to 7 percent above normal (P < 0.001). The softness of the limb tissue was increased (P < 0.001), and elevated skin temperatures were reduced (P < 0.001). There were fewer attacks of secondary acute inflammation (P = 0.01). Bursting pains and feelings of hardness were decreased, as were feelings of tightness, tension, swelling, and heaviness; limb mobility also improved. The active drug was preferred to the placebo by 93 percent of the patients (P < 0.001). Side effects--mild nausea or diarrhea--occurred in seven patients taking the active drug. None withdrew from the trial, and the side effects disappeared after the first month of therapy.\n 5,6-Benzo-[alpha]-pyrone results in slow but safe reduction of lymphedema of the extremities." ]

[ "6376207", "6376208", "3521443", "6863579" ]

[ "The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. I.", "The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. II.", "Comparison of low doses of hydrochlorothiazide plus amiloride and hydrochlorothiazide alone in hypertension in elderly patients.", "Antihypertensive and metabolic effects of hydrochlorothiazide, amiloride-hydrochlorothiazide, and timolol." ]

[ "Chlorthalidone 25 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 25 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reactions.", "Chlorthalidone 50 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 50 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reaction.", "A randomised, double-blind study comparing 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride with 25 mg of hydrochlorothiazide alone was conducted in 40 elderly patients with mild to moderate hypertension. After 8 weeks of treatment, the target blood pressure, supine diastolic blood pressure less than 90 mm Hg, was obtained in 73% of the hydrochlorothiazide plus amiloride treated patients (n = 17) and in 41% of the hydrochlorothiazide treated patients (n = 19; p less than 0.05). However, there was no statistically significant difference in blood pressure reduction between the 2 groups. Four patients dropped out, 3 of them due to side-effects. Serum potassium and magnesium concentrations were reduced in the hydrochlorothiazide group and serum sodium concentration in the hydrochlorothiazide plus amiloride group. Our results suggest that in elderly hypertensive subjects, a higher proportion of patients could be managed with the low dose hydrochlorothiazide plus amiloride regimen than with the low dose hydrochlorothiazide regimen.", "nan" ]

[ "6367554", "3619219", "1854108" ]

[ "Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease.", "Aminophylline for acute exacerbations of chronic obstructive pulmonary disease. A controlled trial.", "Aminophylline therapy for acute bronchospastic disease in the emergency room." ]

[ "Often chronic obstructive pulmonary disease (COPD) patients treated for acute exacerbations receive intravenous (IV) aminophylline in addition to inhaled bronchodilators that may raise serum levels of theophylline into the toxic range. A double-blind, randomized study of 52 men with COPD who came to the emergency department for treatment of exacerbations was initiated to establish the efficacy and safety of this common practice. After history and physical examination, patients were treated with 28% oxygen by Venturi mask and 0.3 cc metaproterenol sulfate in 2.5 cc saline by nebulizer; an IV line was started and patients received either aminophylline or D5W. Measurements included baseline and two-hour serum theophylline levels, pulmonary function tests, and symptom questionnaires. Mean values from the entire group showed decreases in respiratory rate, cardiac rate, and pulsus paradoxus, and increases in forced expiratory volume in one second (FEV1) and vital capacity (VC) over a two-hour treatment period (P less than .01). Despite the increase in serum theophylline in the treatment group, the demographic, clinical, pulmonary function, and outcome data were found to have no statistically significant differences when compared to control patients. The data were then analyzed according to serum theophylline levels. Theophylline level greater than 20 micrograms/mL occurred in 15 patients with no untoward effects; premature ventricular contractions (PVCs) were no more frequent in this group than in those with lower serum theophylline levels. A theophylline level greater than 10 micrograms/mL after two hours of treatment resulted in the following differences, which were not statistically significant: mean FEV1 response less than or equal to 10 micrograms/mL vs greater than 10 micrograms/mL, 20% vs 28%; mean VC change, 17% vs 30%; or mean emergency department returns in one week, 0.1 vs 0.26. In our experience, oxygen and inhaled metaproterenol are effective treatment for exacerbations of COPD.", "Study Objective: To determine the efficacy of intravenous aminophylline in the treatment of patients hospitalized for exacerbation of chronic obstructive pulmonary disease. Design: Randomized, double-blind, placebo-controlled trial during the first 72 hours of hospitalization. Patients: Thirty patients admitted from the emergency room or walk-in clinic with the primary diagnosis of an exacerbation of chronic obstructive pulmonary disease. Twenty-eight patients completed the study; 2 patients, 1 receiving placebo and 1 receiving aminophylline, were removed from the study because of respiratory failure requiring mechanical ventilation. Interventions: Patients received either intravenous aminophylline or placebo, in addition to nebulized, inhaled 0.3 mL of a 5% solution every 6 hours; methylprednisolone, 0.5 mg/kg body weight every 6 hours intravenously; ampicillin, 500 mg orally every 6 hours (tetracycline or trimethoprim-sulfamethoxazole were substituted in penicillin-allergic patients); and supplemental oxygen as needed. Aminophylline infusion rates were adjusted by an unblinded investigator to achieve theophylline levels of 72 to 83 mumol/L. Changes were also made in placebo infusion rates to maintain the double-blind design. Measurements and Main Results: The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before and after metaproterenol inhalation were measured twice daily by a blinded investigator, who also administered a verbal dyspnea index with a scale of 1 to 10 and questioned patients regarding possible side effects of treatment (tremor, palpitations, nausea, or vomiting). Arterial blood gas measurements at 72 hours were compared with those obtained on admission. Significant improvements in FEV1 and FVC measured before and after metaproterenol treatment and in dyspnea occurred over time in both treatment groups (p less than 0.05 for all measurements). However, there were no significant differences between the placebo and aminophylline groups in any of the spirometric measurements or the dyspnea indices (p greater than 0.5 in all five analyses). The mean increases (+/- SE) in Po2 of 1.9 (+/- 0.5) kPa with placebo and 1.7 (+/- 0.7) kPa with aminophylline and the mean decreases in PCO2 of 0.5 (+/- 0.4) kPa with placebo and 1.2 (+/- 0.4) kPa with aminophylline were not significantly different (p greater than 0.6 for PO2, p greater than 0.2 for PCO2).(ABSTRACT TRUNCATED AT 400 WORDS)", "To assess the role of aminophylline in the treatment of acute exacerbations of bronchospastic disease when used in addition to inhaled beta-agonists and intravenous corticosteroids.\n Randomized, double-blind, placebo-controlled intervention study.\n One hundred thirty-three adult patients with either asthma or chronic obstructive pulmonary disease who presented to the emergency department with asthma or wheezing.\n All patients received therapy with both aerosolized metaproterenol and intravenous methyl-prednisolone. Patients were randomly assigned to receive either a loading dose of aminophylline followed by a routine infusion (n = 65) or an equal volume of placebo as a loading dose and infusion (n = 68).\n At discharge from the emergency department, the median serum theophylline concentration for the aminophylline group was 54 mumol/L (9.7 mg/L). The two groups showed no differences (P greater than 0.2) in measurements of forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), or peak expiratory flow rate (PEFR) at baseline or at 60 or 120 minutes after aminophylline administration. Neither patient satisfaction nor physician assessment of response to therapy differed between the two groups. There was no difference (P greater than 0.2) in the frequency of side effects, except for a trend toward a higher frequency of nausea (P = 0.13) in the aminophylline group. There was, however, a threefold decrease in the hospital admission rate for patients treated with aminophylline (6%) compared with placebo recipients (21%) (P = 0.016).\n Aminophylline, in doses producing levels just below the commonly accepted therapeutic range, appears to decrease hospital admissions in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. This finding, if confirmed in larger studies, may represent a substantial cost savings." ]

[ "11220772", "11463108" ]

[ "A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria.", "Clinical trial of beta-arteether versus quinine for the treatment of cerebral malaria in children in Yaounde, Cameroon." ]

[ "The efficacy and safety of intramuscular artemotil (ARTECEF) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens. Rates for negative malaria smears one month after therapy were similar in both groups. Artemotil was a well-tolerated drug in the 48 patients in this study. It appears to be at least therapeutically equivalent to quinine for the treatment of pediatric cerebral malaria. It has the advantage of being able to be given intramuscularly once daily for only five days.", "One hundred and two children aged 0-10 years with cerebral malaria (Blantyre coma score of 2 or less) were randomly treated either with intramuscular arteether (3.2 mg/kg on Day 0, followed by 1.6 mg/kg on Days 1 to 4) or intravenous (i.v.) quinine dihydrochloride (20 mg of the salt/kg, followed by 10 mg of the salt/kg every 8 hr up to Day 6). Treatment with oral quinine sulfate (10 mg/kg every 8 hr) was substituted for i.v. quinine when the patient was able to take oral medicine. All patients were followed up in the hospital for 7 days; thereafter, they were treated as outpatients on Days 14, 21, and 28. Mortality rate, the main efficacy parameter, was 11.8% lower in the arteether treatment group than in the quinine group (15.7% versus 27.4%); however, the difference was not significant (P = 0.25). Means for fever clearance time, coma resolution time, and parasite clearance time were similar in the 2 treatment groups (42.2 +/- 34.9 hr; 34.8 +/- 18.8 hr, and 46.3 +/- 28.5 hr, respectively for arteether, versus 45.0 +/- 26.7 hr; 30.3 +/- 18.9 hr, and 40.7 +/- 18.9 hr, respectively, for quinine). At 28 days, the cure rates were 73.2% and 64.9% for the arteether and quinine treatment groups, respectively. Arteether is safe and therapeutically at least as effective as quinine for the treatment of cerebral malaria in children in Cameroon. Because of its ease of administration, arteether appears to be suited for use in the rural zones where monitoring facilities do not exist." ]

[ "19752847", "12719743", "18033724", "14669295", "17037953", "19574761", "10514756", "19442346", "11407965", "19661790", "17891547", "20386063", "11421145" ]

[ "[Role of interactive music in oncological pediatric patients undergoing painful procedures].", "Music versus distraction for procedural pain and anxiety in patients with cancer.", "A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer.", "Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.", "Use of preferred music to reduce emotional distress and symptom activity during radiation therapy.", "Effectiveness of music therapy for anxiety reduction in women with breast cancer in chemotherapy treatment.", "[Effect of music on children with cancer].", "Effects of a music therapy intervention on quality of life and distress in women with metastatic breast cancer.", "The effect of the bonny method of guided imagery and music on the mood and life quality of cancer patients.", "Exploring the feasibility of a therapeutic music video intervention in adolescents and young adults during stem-cell transplantation.", "Music imagery for adults with acute leukemia in protective environments: a feasibility study.", "Music therapy to reduce pain and anxiety in children with cancer undergoing lumbar puncture: a randomized clinical trial.", "Music as a therapeutic intervention for anxiety in patients receiving radiation therapy." ]

[ "The present study has examined whether interactive music may be considered an effective treatment for the attenuation of anxiety in oncological paediatric patients undergoing painful procedures (lumbar injection, bone marrow aspiration, osteomedullary biopsy and arterial catheter).\n Thirty-nine tumour patients aged between 2 and 12 were randomised into 2 groups: Music (M) (N. 20) and Controls (N. 19) and were treated by M: conscious sedation and intervention of interactive music and C: sedation. The following factors were assessed: temperament on the Emotivity, Activity, Sociability scale, anxiety on the Yale preoperative anxiety scale (mYPAS), the induction compliance checklist (ICC), parent anxiety by cataloguing the trait-state anxiety inventory, and the degree of satisfaction of children, parents and staff using the Barrera questionnaires. Data significance was accepted with values of P<0.05.\n There was a fall in mYPAS values in M compared to C in the four phases of the process: Phase 1 (P<0.05); Phase 2, 3 and 4 (P<0.01). For the ICC children with a score of <or=1, ''collaborated'', those with a score of >1 were ''non collaborators''; in the music group the trend was for an increase in the number of collaborating children (P<0.07).\n The M group presents a significant effect of attenuation of anticipatory anxiety and a tendency to great induction compliance compared to group C. The parents do not show any significant anxiety attenuation effect. The degree of satisfaction of children, parents and staff point to a positive role and a beneficial effect of interactive music on the occasion of painful procedures.", "To test the hypotheses that the effects of a music intervention are greater than those of simple distraction and that either intervention is better at controlling procedural pain and anxiety than treatment as usual.\n Randomized, controlled experiment.\n A midwestern comprehensive cancer center.\n 60 people with cancer having noxious medical procedures such as tissue biopsy or port placement or removal; 58 provided usable data.\n Participants completed measures of pain and anxiety before and after their medical procedures and provided a rating of perceived control over pain and anxiety after the procedure.\n Procedural pain, state anxiety, and perceived control over pain and anxiety.\n Contrary to hypotheses, outcomes achieved with music did not differ from those achieved with simple distraction. Moreover, outcomes achieved under treatment as usual were not significantly different from those obtained with music or distraction interventions. Some patients found that the interventions were bothersome and reported that they wanted to attend to the activities of the surgeon and the medical procedure itself.\n The effects of music, distraction, and treatment as usual are equivocal. In addition, patients have individual preferences for use of distraction during painful or anxiety-provoking procedures.\n Patients having noxious medical procedures should be asked about their desire to be distracted before and during the procedure and offered a strategy that is consistent with their preferences.", "Coping theorists argue that environmental factors affect how children perceive and respond to stressful events such as cancer. However, few studies have investigated how particular interventions can change coping behaviors. The active music engagement (AME) intervention was designed to counter stressful qualities of the in-patient hospital environment by introducing three forms of environmental support.\n The purpose of this multi-site randomized controlled trial was to determine the efficacy of the AME intervention on three coping-related behaviors (i.e. positive facial affect, active engagement, and initiation). Eighty-three participants, ages 4-7, were randomly assigned to one of three conditions: AME (n = 27), music listening (ML; n = 28), or audio storybooks (ASB; n = 28). Conditions were videotaped to facilitate behavioral data collection using time-sampling procedures.\n After adjusting for baseline differences, repeated measure analyses indicated that AME participants had a significantly higher frequency of coping-related behaviors compared with ML or ASB. Positive facial affect and active engagement were significantly higher during AME compared with ML and ASB (p<0.0001). Initiation was significantly higher during AME than ASB (p<0.05).\n This study supports the use of the AME intervention to encourage coping-related behaviors in hospitalized children aged 4-7 receiving cancer treatment.\n (c) 2007 John Wiley & Sons, Ltd.", "High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT.\n Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States.\n Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls.\n Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT.\n Copyright 2003 American Cancer Society.", "Music therapy has decreased anxiety levels in many medical settings. This randomized clinical trial examined the effectiveness of a music listening intervention, delivered by a board-certified music therapist, in patients undergoing curative radiation therapy (RT). Emotional distress (anxiety, depression, and treatment-related distress) and symptoms (fatigue and pain) were measured at baseline, mid-treatment, and end of treatment in 63 patients undergoing RT. Although patients who listened to self-selected music reported lower anxiety and treatment-related distress, there was a decline in these outcomes for patients in both groups over the course of RT. Depression, fatigue, and pain were not appreciably affected by music therapy. Within the music group, there was a significant correlation between number of times music was used/week and the change in treatment-related distress, suggesting that higher doses of music produced greater declines in distress. While these findings provided some support for the use of music in reducing distress during RT, further research demonstrating clear differences between intervention and control conditions is needed. Physical symptoms were not affected by the use of music over the course of RT.", "In the last decade, the public use of complementary and alternative therapies for the solution of various health problems has increased dramatically. Listening to music can be considered a support to the traditional medical practice for the reduction of anxiety and stress related to chemotherapy.", "This study looked for a relationship between immunity and one's spirits while investigating the effect musical therapy produces on Immunoglobulina A (IgA) found in saliva and a Patient's Opinion on the Likert Scale (OPEL). There were 30 children as patients, 15 in a control group and 15 in an experimental group. They were 5 or 16 years of age and checked into the Sant Joan de Deu Hospital in Barcelona due to neoplastic illness.", "This study examined the effects of music therapy (MT), immediate and over time, on patients' psychological functioning, quality of life, and physiologic stress arousal. This intervention, whereby patients use music strategies to cope with cancer-related stressors, is based on a transactional stress-coping framework. Using a longitudinal, randomized controlled design, 70 women with metastatic breast cancer received either MT or usual care. The MT consisted of three individual sessions led by a music therapist. Psychological symptoms were measured with the Hospital Anxiety and Depression Scale and quality of life with the Functional Assessment of Cancer Therapy-General plus a a Spirituality subscale at baseline approximately 6 weeks and 3 months later. Visual analog scales, heart rate, and blood pressure were assessed in the MT group immediately before and after individual session. Significant immediate effects of MT were observed: relaxation, p = < .00001; comfort, p = < . 00001; happiness, p = < .00001; heart rate, p = .0003; although no significant differences between conditions were found over time. A high attrition rate underscored the complexities inherent in conducting intervention research with advanced cancer patients.", "Cancer patients continue to experience elevated levels of emotional distress, even after cancer treatment. Elevated emotional distress negatively impacts immune and endocrine functions and decreases life quality. This study explored the effectiveness of GIM in alleviating mood disturbance and improving quality of life in cancer patients. Eight volunteers with a cancer history were randomly assigned to either an experimental or a wait-list control group. Experimental subjects individually participated in 10 weekly GIM sessions. All subjects completed the Profile of Mood States (POMS) and Quality of Life-Cancer (QOL-CA) questionnaires pretest, posttest, and at a 6-week follow-up. Individuals who participated in GIM sessions scored better on both mood scores and quality of life scores at posttest than those participating in the control group. Additionally, mood and quality of life scores continued to improve in the experimental group, even after sessions were complete. Results indicate that GIM was effective in improving mood and quality of life in these cancer patients.", "The purpose of this study was to explore the feasibility and preliminary efficacy of a therapeutic music video (TMV) intervention for adolescents and young adults (AYAs) undergoing stem-cell transplantation (SCT). Twelve AYAs (aged 11-24 years) were randomized to the TMV or an audio-book protocol. The TMV was designed to diminish symptom distress and improve coping, derived meaning, resilience, and quality of life by supporting AYAs in exploring thoughts and feelings. Six sessions with a board-certified music therapist were held twice a week for 3 weeks. The Adolescent Resilience Model guided the selection of a large, comprehensive battery of outcome measures. Major data collections occurred before admission, after intervention, and at 100 days after transplantation. Participants completed a brief set of measures at presession/postsessions 2, 4, and 6. Rates of consent, session completion, and questionnaire completion supported feasibility. Immediate follow-up measures suggest positive trends in the TMV group for hope, spirituality, confidence/mastery, and self-transcendence. Positive trends at 100 days include MOS, symptoms distress, defensive coping, spirituality, and self-transcendence. Therapeutic music video participants also demonstrated gains in quality of life. The TMV intervention may buffer the immediate after-effects of the stem-cell transplantation experience, and a larger study is warranted.", "Patients receiving intensive chemotherapy can experience increased distressed related to both the cancer diagnosis and treatment isolation. If not addressed, distress can lead to anxiety, depression, and post-traumatic stress disorder. The purpose of this study was to determine the feasibility and possible benefits of a music imagery intervention for patients hospitalized in a protective environment for the treatment of acute leukemia or high-grade non-Hodgkin's lymphoma.\n Adults receiving intensive myelosuppressive chemotherapy in a protective environment were randomized to standard care or standard care plus music imagery. The music imagery sessions occurred twice weekly for up to eight sessions. Patients were encouraged to use the music imagery daily.\n The principal criteria of feasibility were rate of consent, rate of completion of scheduled sessions, and rate of questionnaire completion. Forty-nine out of 78 patients consented, a 63% consent rate. Seventy-two percent of all scheduled music imagery sessions were completed. The rate of questionnaire completion was 60% with missing data because of illness severity and early discharge. The principal outcomes of benefit (e.g., efficacy) were positive and negative affects, fatigue, and anxiety. Both groups improved over time on all outcomes (all p < 0.001). However, a subgroup of individuals with low baseline negative affect who received the intervention reported significantly less anxiety at discharge than individuals with low baseline negative affect who did not receive the intervention.\n Music imagery is feasible for adults with acute leukemia in protected environments. Patients with lower initial distress may benefit from a music imagery program in terms of reduced anxiety at discharge.", "A nonpharmacological method can be an alternative or complement to analgesics.The aim of this study was to evaluate if music medicine influences pain and anxiety in children undergoing lumbar punctures. A randomized clinical trial was used in 40 children (aged 7-12 years) with leukemia, followed by interviews in 20 of these participants. The participants were randomly assigned to a music group (n = 20) or control group (n = 20). The primary outcome was pain scores and the secondary was heart rate, blood pressure, respiratory rate, and oxygen saturation measured before, during, and after the procedure. Anxiety scores were measured before and after the procedure. Interviews with open-ended questions were conducted in conjunction with the completed procedures. The results showed lower pain scores and heart and respiratory rates in the music group during and after the lumbar puncture. The anxiety scores were lower in the music group both before and after the procedure. The findings from the interviews confirmed the quantity results through descriptions of a positive experience by the children, including less pain and fear.", "To determine whether music moderates the level of anxiety that patients experience during radiation therapy.\n Experimental, longitudinal, random assignment to music or no music therapy.\n Urban radiation oncology center in a Department of Veterans Affairs hospital in the southeastern United States.\n Forty-two men (19 in the experimental group, 23 in the control group) aged 39-80 years (74% white, 12% African American, 12% Hispanic, and 2% other) receiving definitive external beam radiation therapy for pelvic or abdominal malignancies.\n Patients in the experimental group listened to music of their choice provided via audiotapes and headphones before and during their simulation and daily treatments for the duration of the planned course of therapy. The control group received standard care. The State-Trait Anxiety Inventory was administered initially to participants in both groups at the time of evaluation (time 1), post-simulation (time 2), at the end of the first week (time 3), at the end of the third week (time 4), and at the end of the fifth week or end of radiation therapy (time 5).\n State anxiety.\n No significant difference existed between the two groups to suggest that music moderated the level of anxiety during radiotherapy. However, post-hoc analyses identified changes and trends in state anxiety scores, suggesting a possible benefit of music therapy during radiotherapy.\n Despite a lack of group differences, early intervention with music therapy for patients with high levels of anxiety may be beneficial.\n Nurses and other clinicians may administer state anxiety scales at the initial visit or prior to pretreatment radiation planning (simulation). Individuals who have high state anxiety scores may receive nursing interventions tailored to reduce anxiety during simulation and the early part of radiotherapy." ]

[ "7002206", "1835005", "15512177", "3685399", "1872778", "8238173" ]

[ "Reduction of menstrual blood loss by danazol in unexplained menorrhagia: lack of effect of placebo.", "A comparative study of danazol and norethisterone in dysfunctional uterine bleeding presenting as menorrhagia.", "A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia.", "The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia.", "Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia.", "A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia." ]

[ "In women with menorrhagia of unknown cause, the efficacy of the drug danazol in reducing heavy menstrual blood loss was investigated making objective measurements of menstrual blood loss. Drug regimens tested were daily administration of 200 or 100 mg danazol for 12 weeks and daily danazol given in the luteal phase or during menstruation. The results suggest that 200 mg danazol daily is the most acceptable regimen clinically since it significantly reduced menstrual blood loss and was associated with a relatively low incidence of side effects. In 16 women on this dose menstrual blood loss was suppressed from a mean pre-treatment loss of 183 +/- 25 ml to 38 +/- 11 ml (p < 0.01) in the second, and 26 +/- 9 ml (p < 0.01) in the third treatment months. The majority of women had regular episodes of bleeding with no alteration in cycle length and a reduction in the number of days of bleeding. Although 100 mg daily suppressed menstrual blood loss, particularly by the third month of treatment, it increased the number of episodes of bleeding in some women which they found unacceptable. Both 200 mg and 100 mg relieved dysmenorrhoea in the majority of women presenting with the symptoms. Danazol taken daily in the early follicular or luteal phase of the menstrual cycle did not significantly alter menstrual blood loss. There was no effect of placebo therapy on measured menstrual blood loss in a single blind trial in eight women with menorrhagia.", "This randomized open study compared the efficacy and safety of norethisterone, 5 mg three times a day from day 19 to 26, and danazol, 200 mg daily, in the treatment of dysfunctional uterine bleeding presenting as menorrhagia. Clinical criteria were employed to confirm the diagnosis, and subjective assessment of the condition was performed during one pre-treatment and three treatment cycles. Fourteen patients commenced norethisterone and 10 danazol. Bleeding intensity scores were significantly lower with danazol than with norethisterone, and patients assessed their blood loss to be significantly less with danazol than with norethisterone. Associated symptoms of backache and abdominal pain were improved to a similar degree by both treatments. Adverse reactions were reported with similar frequency and were of a similar nature in both treatment groups.", "A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group.", "The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and \"total\" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism.", "A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient.", "Our purpose was to compare the efficacy of the recommended dose of danazol, a reduced-dose danazol regimen, and norethindrone in the treatment of objectively proven menorrhagia. Recurrence after discontinuing treatment was also assessed.\n The study was a single-blind, randomized, parallel, comparative study. After a placebo run-in period over two menstrual cycles, 57 patients with a baseline mean menstrual blood loss of at least 80 ml per cycle were randomly assigned to receive one of three therapies: danazol, 200 mg/day (n = 19) for three menstrual cycles; danazol, 200 mg/day for one cycle, 100 mg/day for one cycle, and 50 mg/day for one cycle (n = 19); and norethindrone, 5 mg three times daily on days 19 through 26 of the cycle for three consecutive cycles (n = 19). Patients in whom treatment was successful (those experiencing blood loss < 80 ml) were entered in the follow-up phase of the study, receiving placebo for a maximum of four menstrual cycles.\n The final menstrual blood loss on treatment was significantly less for those patients who received both danazol regimens compared with those who received norethindrone (p = 0.017 for reducing dose danazol vs norethindrone and p = 0.043 for 200 mg of danazol vs norethindrone). Both danazol treatment regimens were significantly more successful in reducing menstrual blood loss to within the normal range than was norethindrone. The reducing-dose danazol regimen was successful in eight of 17 patients (p = 0.027), and 200 mg of danazol was successful in nine of 19 patients (p = 0.029), compared with the two successes of 18 patients treated with norethindrone. Significantly more recipients of 200 mg of danazol than of norethindrone subjectively rated their treatment to be moderately or highly effective (p = 0.033). Both danazol treatment regimens were associated with a higher incidence of adverse events than was norethindrone therapy, although the number of withdrawals were similar and infrequent in the three groups.\n Both danazol regimens were significantly more effective than norethindrone in reducing the excessive menstrual blood loss of women with unexplained menorrhagia. A subjective assessment by patients found that only the 200 mg of danazol was judged to be significantly more effective than norethindrone in controlling the heaviness of menstrual bleeding. The reduced-dose danazol regimen did not appear to markedly diminish the incidence of adverse events compared with the 200 mg of danazol regimen." ]

[ "2948162", "6228772", "6232359", "2934008", "2944997", "10485505", "6212554" ]

[ "Comparison of etodolac, aspirin and placebo for pain after oral surgery.", "The effectiveness of 100 and 200 mg etodolac (Ultradol), aspirin, and placebo in patients with pain following oral surgery.", "The efficacy of etodolac for patients with pain following oral surgery.", "Relief of dental surgery pain: a controlled 12-hour comparison of etodolac, aspirin, and placebo.", "Comparison of etodolac, zomepirac, and placebo for relief of pain after oral surgery.", "Conventional and extended-release etodolac for postsurgical dental pain.", "Etodolac in postsurgical pain: a double-blind dose-ranging efficacy study with aspirin and placebo." ]

[ "Single oral doses of etodolac 50, 100 and 200 mg were compared with aspirin 650 mg and placebo in a double-blind, parallel group study of 189 outpatients reporting moderate or severe pain after oral surgery. Overall efficacy of test drugs was evaluated by sum of pain intensity difference (SPID) scores and total pain relief (TOTPAR) scores over 0.5-3, 0.5-6, 0.5-8 and 0.5-12 hours. Etodolac 200 mg provided significantly greater analgesia than aspirin by these measurements over all SPID and all but one TOTPAR interval, and was significantly more effective than placebo over all intervals. Etodolac 100 mg was superior to aspirin for SPID 0.5-8 and 0.5-12 hours, and superior to placebo for both SPID and TOTPAR over all time intervals. Onset of analgesia for etodolac 100 mg, 200 mg and aspirin was 1 hour or less for the majority of patients in each group; 42% receiving etodolac 200 mg reported onset of analgesia within 0.5 hour. Duration of analgesia for etodolac 200 mg appeared twice that of aspirin. A significant positive dose-response relationship was obtained for the three doses of etodolac. A low frequency of side effects was observed in all treatment groups.", "The analgesic efficacy of etodolac (Ultradol) was evaluated in 168 patients experiencing moderate to severe pain following oral surgery. The patients were given either etodolac 100 mg, etodolac 200 mg, aspirin 650 mg, or placebo. There was a minimum of forty patients in each drug group. Patients recorded pain intensity and pain relief at 1/2 hour and then hourly for up to 12 hours after medication. The efficacy variables analyzed were the sum of pain-intensity differences, total pain relief, onset of analgesia, and the patient's opinion of the study drug. Time-effect curves were made from the pain-relief and pain-intensity difference scores. The analgesic potency of both 100 and 200 mg of etodolac was comparable to 650 mg of aspirin and superior to placebo. Like aspirin, both doses of etodolac showed significant analgesia within one hour and a significantly longer duration of action than placebo.", "The analgesic efficacy of etodolac for 161 patients reporting moderate to severe pain after oral surgery was evaluated. The patients were given single oral doses of one of the following test drugs--aspirin, 650 mg; etodolac, 50 mg; or etodolac, 200 mg--or placebo. There were at least 39 patients in each drug group. After medication, patients recorded pain intensity and pain relief at half-hour intervals for the first hour and then hourly for up to eight hours. Pain intensity differences, total pain relief, onset of analgesia, and each patient's overall opinion of the drug were analyzed. Time--effect curves were derived from the pain relief and pain intensity difference scores. Analgesic effects produced by both doses of etodolac were comparable with those of 650 mg of aspirin. All active drugs were significantly more effective than placebo, and the 200-mg dose of etodolac provided an earlier onset and longer duration of analgesia than the other test drugs.", "Single doses of the study drugs were evaluated for 12 hours by 201 out-patients reporting moderate or severe pain following oral surgery. The results of this double-blind study indicated that 50, 100, and 200 mg of etodolac as well as 650 mg of aspirin were significantly more effective than placebo. A dose-response relationship was found for the three doses of etodolac, which was significant for summed pain relief scores for up to 8 hours. In terms of total analgesic effect, etodolac 200 mg was significantly superior to placebo for 8 hours, while aspirin and the two lower doses of etodolac were similarly effective in the range of 3-6 hours postdrug. All doses showed a favorable onset of analgesia (½-1 hour). Etodolac 200 mg resulted in a duration of action which was approximately twice as long as aspirin's and also produced a peak pain relief which was significantly greater than the lower doses of etodolac and aspirin. All study medications were well tolerated with no reports of significant adverse side effects. No dose-related effects were observed with etodolac", "A double-blind, randomized study of 137 patients compared the effectiveness of single doses of etodolac, 200 and 400 mg, zomepirac, 100 mg, and placebo in relieving moderate to severe pain following third molar extractions. Throughout the 12-hour evaluation period, doses of both etodolac and zomepirac were significantly superior to placebo for total analgesic effect, as measured by the sum of pain intensity difference (SPID) and sum of pain relief (TOTPAR) scores. However, there were no significant differences among the active drugs. It was concluded that etodolac, 200 and 400 mg, provides analgesic efficacy comparable to that of zomepirac, 100 mg, and superior to that of placebo.", "This double-masked, parallel-group, randomized study compared the analgesic efficacy and tolerability of a single investigational 1200-mg dose of extended-release etodolac with those of a single 400-mg dose of extended-release etodolac and twice-daily doses of conventional etodolac 200 and 400 mg and placebo given 8 hours apart in 237 patients with moderate or severe postoperative pain following surgical removal of > or = 2 impacted third molars. Both doses of conventional etodolac and the 1200-mg dose of extended-release etodolac were significantly more effective on all summary analgesic measures than placebo (P < 0.05). Conventional etodolac had an onset of analgesic activity within 45 (400 mg) to 60 (200 mg) minutes and an analgesic duration of 5 to 6 hours. Extended-release etodolac 1200 mg had an onset of action within 60 minutes and an analgesic duration of 12 to 24 hours. At hours 2 and 3, conventional etodolac 400 mg was significantly more effective than the other treatments; from hours 6 through 12, extended-release etodolac 1200 mg was significantly more effective than the other treatments (both, P < 0.05). No serious adverse events were observed in this study, with an incidence of side effects in the active etodolac groups no different than that with placebo. Extended-release etodolac 1200 mg has a prolonged analgesic duration and an acceptable side-effect profile in the oral surgery pain model.", "A study was conducted to compare the analgesic activity of single oral doses of etodolac (25, 50, 100, 200, and 400 mg) with 650 mg aspirin and placebo. A total of 146 patients with moderate or severe pain from orthopedic or urologic interventions received one of the test medications 13-25 h after the beginning of surgery and according to a randomized allocation balanced as to initial pain intensity. Data for pain intensity and pain relief were collected at 1/2 h and then hourly for 8 h. Vital signs and adverse reactions were also recorded. One hundred and forty-two patients completed the study: four were excluded because of protocol deviations. The average response to 100, 200, and 400 mg of etodolac was superior to that of placebo. On the basis of SPID, TOTPAR, and duration of analgesia, 400 mg etodolac was also significantly more effective than 650 mg aspirin. Mild side effects probably or possibly related to etodolac were reported by three patients. This study provides evidence that etodolac in doses of 100 mg and higher is an effective and well-tolerated analgesic." ]

[ "15363008", "14586050", "21311842" ]

[ "Trial of nurse-run asthma clinics based in general practice versus usual medical care.", "Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up.", "Paediatric asthma outpatient care by asthma nurse, paediatrician or general practitioner: randomised controlled trial with two-year follow-up." ]

[ "The aim of this study was to assess the ability of nurse-run asthma clinics based in general practice compared with usual medical care to produce at least a moderate improvement in the quality of life of adults with asthma.\n A randomized controlled trial involving 80 asthma clinic and 90 usual medical care asthma participants, aged 18 years and older was conducted in 11 general practices in Adelaide. The main outcome measure was the St George's respiratory questionnaire (SGRQ), from which quality-of-life scores were used to assess therapeutic benefit. Lung function measurements and health services utilization data were also collected.\n One hundred and fifty-three participants (90%) were reviewed at follow up after 6-9 months. There was little difference between groups in baseline measures or for the 6-month follow-up outcomes, including the mean difference in total SGRQ scores (-0.5, 95% confidence interval (CI) -4.0, 2.9) and the mean difference in percentage predicted FEV(1) (2.3%, 95% CI -0.7, 5.3 pre-bronchodilator; 0.4%, 95% CI -5.1, 5.9 post-bronchodilator). Trends in health services utilization were noted.\n Nurse-run asthma clinics based in general practice and usual medical care were similar in their effects on quality of life and lung function in adults. These findings cannot be generalized to hospital outpatients and other clinics that manage more severe asthmatic patients.", "Until now, care provided by asthma nurses has been additional to care provided by paediatricians. A study was undertaken to compare nurse led outpatient management of childhood asthma with follow up by a paediatrician.\n Seventy four children referred because of insufficient control of persistent asthma were randomly allocated to 1 year follow up by a paediatrician or asthma nurse. The main outcome measure was the percentage of symptom-free days. Additional outcome measures were airway hyperresponsiveness, lung function, daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of additional visits to the general practitioner, absence from school, functional health status, and disease specific quality of life.\n There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI -8.8 to 13.8), airway hyperresponsiveness (log10 PD20 0.06; -0.19 to 0.32), functional health status (10.1; -0.3 to 19.8), disease specific quality of life of patients (0.08; -0.9 to 0.7), and disease specific quality of life of caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome parameters improved considerably over the 1 year study period. These improvements were achieved although the daily dose of ICS was reduced by a mean of 26% compared with the dose received by children at referral. All parents were satisfied with the asthma care received.\n After initial assessment in a multidisciplinary clinic, childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician. During close follow up by paediatrician or asthma nurse, asthma control improved despite a reduction in ICS dose.", "For children with stable asthma, to test non-inferiority of care provided by a hospital-based specialised asthma nurse versus a general practitioner (GP) or paediatrician.\n Randomised controlled trial evaluating standard care by a GP, paediatrician or an asthma nurse, with two-year follow-up.\n 107 children were recruited, 45 from general practice and 62 from hospital. After two years, no significant differences between groups were found for airway responsiveness, FEV1, asthma control, medication, school absence or parental work absence. In the general practice group there was a significantly lower frequency of regular review visits ('regular' = at least one review per six months) compared to the paediatrician and specialised asthma nurse group, both after one year [45.7% versus 87.9% and 94.3%, respectively, (p<0.0005)] and after two years [26.5% versus 87.9% and 75.8%, respectively, (p<0.0005)]. We found no significant differences in unplanned visits. In most cases the asthma nurse was able to provide care without consultation with the paediatrician.\n The degree of disease control in stable childhood asthma managed by an asthma nurse is not inferior to traditional management by primary or secondary care physicians. The results also suggest that a lower review frequency does not detract from good disease control." ]

[ "16399189", "11556862", "12049562", "15839866", "11700188", "17071297", "15195050" ]

[ "Comparison of posttonsillectomy pain using the ultrasonic scalpel, coblator, and electrocautery.", "Traditional tonsillectomy compared with bipolar radiofrequency thermal ablation tonsillectomy in adults: a pilot study.", "Tonsillectomy by means of plasma-mediated ablation: prospective, randomized, blinded comparison with monopolar electrosurgery.", "A double-blinded randomized controlled trial of coblation versus conventional dissection tonsillectomy on post-operative symptoms.", "Paediatric coblation tonsillectomy.", "Coblation vs electrocautery tonsillectomy: postoperative recovery in adults.", "Pediatric total tonsillectomy using coblation compared to conventional electrosurgery: a prospective, controlled single-blind study." ]

[ "To compare postoperative tonsillectomy pain between 3 commonly used surgical devices: the Harmonic Ultrasonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH), the Coblator (ArthroCare Corp, Sunnyvale, CA), and electrocautery.\n A prospective, randomized trial. One hundred thirty-four patients were randomly assigned to receive a tonsillectomy with 1 of 3 surgical devices. All patients were asked to fill out a postoperative diary.\n Statistically significant differences in pain scores were revealed between the Coblator and electrocautery (P = 0.02) and between the Coblator and the Ultrasonic Scalpel (P = 0.003), with the Coblator having lower pain scores. Electrocautery and the Ultrasonic Scalpel did not differ significantly from each other. The Coblation method showed a strong trend toward quicker return to normal diet.\n Patients undergoing tonsillectomy with the Coblator device reported less pain over a 10-day period than patients undergoing tonsillectomy with electrocautery or the Ultrasonic Scalpel. Pain after tonsillectomy remains a major issue for our patients. The choice of surgical instrument appears to be one way to reduce this pain. EBM rating: A-1b.", "To assess the morbidity and efficacy of bipolar radiofrequency thermal ablation tonsillectomy and compare it with traditional cold dissection tonsillectomy with diathermy hemostasis.\n Prospective, randomized, single-blinded, controlled clinical study.\n Helsinki University Central Hospital, Department of Otorhinolaryngology-Head & Neck Surgery, Helsinki, Finland.\n Forty healthy volunteer patients aged 18 to 65 years admitted for elective tonsillectomy with recurrent or chronic tonsillitis, obstructive tonsillar hypertrophy, or history of quinsy. Two patients were excluded from the study and 1 patient cancelled the operation.\n Nineteen patients underwent a traditional cold dissection tonsillectomy with diathermy hemostasis, and 18 patients underwent a bipolar radiofrequency thermal ablation tonsillectomy. There was no intergroup difference in age, sex, weight, and indications for tonsillectomy. The subjects were not informed of the type of procedure until the telephone interview 3 weeks after the operation.\n Operating time and intraoperative blood loss; need for anesthetics during the operation; different recovery indicators in the recovery room (ie, duration and medications administered), surgical ward (ie, medications administered, use of corticosteroids, general condition, and status of the uvula on the first postoperative day), and in the 2 weeks following surgery (ie, visual analog scale scores on 6 symptoms, medications needed, the day patients returned to work, use of antibiotics, and retreatment acceptance); and complications and certain laboratory parameters.\n There was a statistically significant but clinically insignificant difference in operating time and intraoperative blood loss in favor of the traditional tonsillectomy group. The other outcome measures showed no statistically significant differences.\n Bipolar radiofrequency thermal ablation and traditional tonsillectomy were associated with similar postoperative morbidity.", "To compare plasma-mediated ablation (PMA) with monopolar electrosurgery (MES) for pediatric tonsillectomy.\n Prospective, randomized, blinded study.\n Academic children's hospital.\n Thirty-four children, aged 4 to 7 years.\n Tonsillectomy by means of PMA (n = 17) or MES (n = 17).\n We measured surgical efficacy, estimated blood loss, and surgical time during tonsillectomy and morphine use, immediate postoperative pain, and recovery scores after tonsillectomy. Parents recorded recovery of normal diet and activity and their own return to work for 10 days after surgery. Histopathologic evaluation of excised tonsils was performed. We reviewed medical records and attempted follow-up telephone contact.\n With no significant difference in blood loss compared with MES, PMA was effective for tonsillectomy. Performance of PMA took longer (24 vs 16 minutes; P =.002). Results of histopathologic evaluation showed less thermal injury with PMA than with MES (P =.03). Morphine consumption, pain, and recovery scores were equivalent between groups. We found no significant difference in recovery of normal diet and activity or parental return to work. Patients undergoing PMA had a greater number of perioperative complications than those undergoing MES, including 2 patients in the PMA group (compared with none in the MES group) who required unplanned admission for postoperative airway obstruction.\n Plasma-mediated ablation for pediatric tonsillectomy resulted in less histopathologic thermal injury than MES, but did not show a statistically faster recovery to normal activity and diet or parental return to work. In addition, PMA took longer to perform, and had more complications. Therefore, PMA should not replace MES for pediatric tonsillectomy. The reduced thermal injury with PMA supports investigation into other means of using plasma ablation to treat tonsillar hypertrophy.", "The aim of this study was to compare postoperative symptoms following coblation tonsillectomy with those experienced following a traditional cold dissection.\n A prospective randomized controlled trial.\n Secondary otorhinolaryngology care.\n Ninety-two adult patients with recurrent tonsillitis meriting tonsillectomy were recruited and randomly allocated into either coblation or cold dissection tonsillectomy groups.\n Primary outcomes were post-operative pain, otalgia, swallowing and analgesia use at 6-8 hours, 1, 3, 7 and 14 days post-operative. Secondary outcomes were post-operative day returned to eating and returned to normal activities/work.\n No significant differences between the two groups (P >or= 0.1) were found in any of the above primary outcomes, apart from swallowing at 6-8 hrs post-operatively where the cold dissection group had less pain. This group also returned earlier to normal eating (P = 0.03). The power of the study was sufficient to show a difference in the visual analogue scores of 2 between groups.\n The use of coblation to perform tonsillectomy does not confer any symptomatic benefits to the patient over conventional cold dissection tonsillectomy.", "Tonsillectomy has been described using a number of techniques. Recently Coblation Technology has been used to remove tonsils with anecdotal evidence of a reduction in post-operative morbidity. In this study we aim to see if there is any difference in post-operative pain, tonsillar fossae healing and return to a normal diet performing tonsillectomy, using tissue coblation compared with standard bipolar dissection.\n A double blind randomised control trial to compare the technique of tissue coblation with standard bipolar dissection to remove tonsils in 38 children on the waiting list for tonsillectomy, with a history of chronic tonsillitis or obstructive tonsils.\n A significant reduction in post-operative pain was found in the children whose tonsils were removed by tissue coblation (P<0.0001). More rapid healing of the tonsillar fossae was found in the coblation group. Children who had their tonsils removed by coblation were found to return to their normal diet far sooner than those who underwent bipolar dissection. There were no episodes of primary or secondary haemorrhage in either group.\n This new technique using tissue coblation for tonsil removal offers significant advantages in the post-operative period, with rapid return to a normal diet and a drastic reduction in analgesic requirements following the surgery.", "Comparison of coblation and monopolar electrocautery tonsillectomy in terms of postoperative pain and recovery.\n Prospective double-blind randomized controlled trial.\n Patients with recurrent tonsillitis requiring tonsillectomy were randomized to 2 groups: coblation or monopolar electrocautery tonsillectomy. Postoperative pain, complications, and days taken to return to work and normal diet were compared and analyzed with the aid of a pain diary, given to the patient.\n 67 patients were recruited. Patients undergoing coblation tonsillectomy were able to return to normal diet in a shorter space of time following surgery. Patients undergoing coblation tonsillectomy were more likely to recommend the surgery than patients undergoing electrocautery tonsillectomy. No significant differences in the daily visual analog score for pain were seen for both groups of patients.\n Our results showed that coblation tonsillectomy has a faster recovery period and may offer advantages when compared to monopolar electrocautery tonsillectomy.", "Postoperative recovery after tonsillectomy using Coblation excision (CES) was compared with conventional electrosurgery (ES).\n Patients aged 3 to 12 years from 3 clinical sites were randomly assigned and blinded to receive tonsillectomy using CES (n = 44) or ES (n = 45).\n Operative parameters did not differ between groups. Return to normal diet, activity, and pain-free status were similar, although fewer CES patients contacted the physician regarding postoperative complications (33% vs 54%; p = 0.081), experienced nausea (35% vs 62%, p = 0.013), or had localized site-specific swelling (p < 0.05) during the 2 weeks after surgery. In addition, CES children tended to discontinue prescription narcotics 1 day earlier than ES patients (7 vs 8 days, p = 0.071) and took one half as many daily doses. More CES than ES parents rated the postoperative experience as 'better than expected' (79% vs 60%, p = 0.055).\n Children who received CES tonsillectomy appeared to experience a better quality postoperative course, with no detriment to operative benefits of conventional electrosurgery." ]