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[ "12352419", "8800888", "12629374", "12187222", "7685429", "10233489", "8881949", "10100361", "10591258", "10524887", "10840426", "10532976", "10213108", "8579313", "8560661", "10840425", "7542818", "12460345", "9764453", "10604701", "9586609", "7544932" ]

[ "Transurethral holmium laser enucleation versus transvesical open enucleation for prostate adenoma greater than 100 gm.:: a randomized prospective trial of 120 patients.", "A step towards day case prostatectomy.", "A randomized controlled trial comparing transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia: analysis of subjective changes, morbidity and mortality.", "A randomized controlled trial comparing transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia: urodynamic effects.", "Laser prostatectomy performed with a right angle firing neodymium:YAG laser fiber at 40 watts power setting.", "A prospective randomized controlled trial of hybrid laser treatment or transurethral resection of the prostate, with a 1-year follow-up.", "A comparative study of laser ablation and transurethral electroresection for benign prostatic hyperplasia: results of a 6-month follow-up.", "Contact laser prostatectomy compared to TURP in prostatic hyperplasia smaller than 40 ml. Six-month follow-up with complex urodynamic assessment.", "Randomized trial of safety and efficacy of transurethral resection of the prostate using contact laser versus electrocautery.", "Holmium laser versus transurethral resection of the prostate: a randomized prospective trial with 1-year followup.", "A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.", "Hybrid laser treatment compared with transurethral resection of the prostate for symptomatic bladder outlet obstruction caused by a large benign prostate: a prospective, randomized trial with a 6-month follow-up.", "Randomized comparison of transurethral electroresection and holmium: YAG laser vaporization for symptomatic benign prostatic hyperplasia.", "A randomised single institution study comparing laser prostatectomy and transurethral resection of the prostate.", "The Oxford Laser Prostate Trial: sensitivity to change of three measures of outcome.", "A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.", "A prospective randomized comparison of transurethral resection to visual laser ablation of the prostate for the treatment of benign prostatic hyperplasia.", "Transurethral interstitial laser coagulation of the prostate and transurethral microwave thermotherapy vs transurethral resection or incision of the prostate: results of a randomized, controlled study in patients with symptomatic benign prostatic hyperplasia.", "A randomized prospective study of transurethral electrovaporization vs laser ablation of the prostate in men with benign prostatic hypertrophy.", "A randomized prospective study of laser ablation of the prostate versus transurethral resection of the prostate in men with benign prostatic hyperplasia.", "Holmium laser resection of the prostate versus neodymium:yttrium-aluminum-garnet visual laser ablation of the prostate: a randomized prospective comparison of two techniques for laser prostatectomy.", "A multicenter, randomized, prospective study of endoscopic laser ablation versus transurethral resection of the prostate." ]

[ "Prostate adenomas greater than 100 gm. have traditionally been treated with open prostatectomy. This procedure may involve considerable blood loss, morbidity, prolonged hospital stay and recovery time. The high powered holmium:YAG laser can be used endoscopically to enucleate obstructing prostatic tissue in a relatively bloodless manner. The technique of transurethral holmium laser enucleation of the prostate is compared to open prostatectomy for the surgical management of large prostate adenomas in a prospective randomized study.\n A total of 120 urodynamically obstructed patients with a prostate larger than 100 gm. on transrectal ultrasound were randomized to undergo holmium laser enucleation of the prostate or open prostatectomy. All patients were assessed preoperatively and 1, 3 and 6 months postoperatively. Patient baseline characteristics, perioperative data and postoperative outcome were compared. All complications were noted.\n Holmium laser enucleation of the prostate and open prostatectomy resulted in a similar and significant improvement in American Urological Association symptom scores, peak urinary flow rates and post-void residual urine volumes. Operating time was significantly longer in the holmium group but blood loss was significantly less, and catheterization time and hospital stay were significantly shorter. Effects on continence and potency were similar in both groups but adverse events were less frequent in the holmium group. None of the holmium group patients needed blood transfusions in contrast to 8 patients in the prostatectomy group.\n Holmium laser enucleation of the prostate and open prostatectomy are equally effective procedures for removal of large prostatic adenomas. Holmium laser enucleation resulted in significantly less perioperative morbidity and may become the endourological alternative to open prostatectomy.", "To compare laser prostatectomy, using both side-fire and contact lasers, with transurethral resection of the prostate (TURP) to identify the advantages and disadvantages of all three in the short-and long-term (1 year).\n Forty patients were randomized into one of four groups undergoing TURP, side-fire laser prostatectomy alone, side-fire with debridement and contact laser prostatectomy. Strict entry criteria ensured that no patients with malignancy were selected. The patients were reviewed after 3, 6 and 12 months.\n The duration of operation and length of hospital stay were significantly shorter in those undergoing laser side-fire treatment than those undergoing TURP. However, the early (3-month) symptom score was significantly worse in those treated by side-fire laser than in those treated by side-fire laser with debridement. After 1 year there was no significant difference in mean symptom score and mean urinary flow rate among the four groups.\n Laser prostatectomy offers the prospect of a shorter theatre and hospital stay and, by debriding the thermocoagulated tissue, the early irritative symptoms were reduced, with a significant improvement in symptom score after 3 months in patients with small prostates.", "We analyze subjective changes, morbidity and mortality in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) after transurethral resection of the prostate, contact laser prostatectomy and electrovaporization.\n A prospective, randomized controlled trial was conducted on men with lower urinary tract symptoms, who met the criteria of the International Scientific Committee on BPH, had a prostate volume between 20 and 65 ml., and had Schäfer's obstruction grade 2 or greater. Objective morbidity was recorded for up to 12 months. Subjective morbidity was measured by a questionnaire completed by patients. Subjective changes were quantified using the International Prostate Symptom Score, Symptom Problem Index, Quality of Life question and BPH Impact Index. These indexes and the morbidity questionnaire were measured weekly for the first 6 weeks postoperatively and then at 3, 6 and 12 months.\n Transurethral prostatic resection was analyzed in 50 men, laser treatment in 45 and electrovaporization in 46. Baseline characteristics, and changes in the symptom scores up to 12 months postoperatively were similar. Perioperative blood loss and perforation were greatest in the resection group, and retention was greatest in the laser group. During the first 6 postoperative weeks there was less pain and less hematuria after resection, and less incontinence after laser prostatectomy.\n Subjective changes are similar for transurethral prostatic resection, contact laser and electrovaporization. In the first 6 weeks after treatment there are only slight differences in pain, hematuria and incontinence among the therapies.", "We compared urodynamic and uroflowmetry improvements in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) after transurethral prostate resection, contact laser prostatectomy and electrovaporization.\n A prospective randomized controlled trial was performed in men with lower urinary tract symptoms suggestive of BPH who met the criteria of the International Scientific Committee on BPH, had a prostate volume of between 20 and 65 ml., and a Schäfer obstruction grade of 2 or greater. Before and 6 months after treatment urodynamics and free uroflowmetry were performed.\n A total of 50, 45 and 46 men were randomized to transurethral prostate resection, laser treatment and electrovaporization, respectively. Baseline characteristics were similar in the 3 groups. Detrusor contractility did not change in any of the treatment groups. The average maximum free flow rate increased by a factor of 2.4 after transurethral prostate resection, 2.5 after laser prostatectomy and 2.4 after electrovaporization. The Schäfer obstruction grade decreased by a factor of 0.3 in all groups. Obstruction (Schäfer grade greater than 2) was not noted after transurethral prostate resection or electrovaporization but it was evident in 2 patients after laser prostatectomy. Effective capacity increased by a factor of 1.5 or more. The incidence of detrusor instability was decreased by half in all groups. The incidence of significant post-void residual urine volume decreased in all groups.\n There were no significant differences in the improvement in urodynamic and uroflowmetry parameters 6 months after treatment when comparing transurethral prostate resection, contact laser prostatectomy and electrovaporization in men with lower urinary tract symptoms suggestive of BPH.", "A total of 25 patients with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia was entered into a prospective, randomized trial comparing laser prostatectomy performed with the Urolase right angle firing neodymium:YAG laser fiber to standard transurethral electroresection of the prostate. Overall acute perioperative morbidity, including blood loss and fluid absorption, was significantly less for patients undergoing laser prostatectomy. Efficacy of treatment was assessed by standardized American Urological Association symptom scores, patient assessment of symptom improvement, peak urinary flow rates and post-void residual urine volumes, and was equivalent for the 2 treatment groups at 3 and 6 months.", "To compare the clinical outcome after hybrid laser treatment of the prostate, combining potassium titanyl phosphate (KTP) and Nd:YAG lasers, with transurethral resection of the prostate (TURP).\n A prospective randomized trial was conducted to compare laser treatment and TURP. The hybrid laser treatment technique involved performing initial 30 W KTP vaporizing bladder neck incisions and prostatotomies followed by a 'free-paint' application of 60 W Nd:YAG coagulation energy. Patients were re-assessed after 6 weeks, 6 months and 1 year, using the International Prostate Symptom Score (IPSS) and uroflowmetry. TURP was conducted using conventional methods.\n In all, 204 patients were randomized into the study; at 6 weeks there were significant differences between the groups for the IPSS (12.4 vs 9.1, P=0.001) and maximum urinary flow rates (16.1 vs 20.8 mL/S, P<0. 001) in favour of the TURP group. At 6 months and one year this difference had disappeared. Similar numbers of patients in each group complained of bothersome postoperative urinary symptoms (23% vs 19%). Blood transfusions (5% vs none) and urethral strictures (9% vs 2%) were more common after TURP, whereas more early infective complications occurred after hybrid laser treatment (24% vs 5%). Only one patient in each group required re-operation because of poor resolution of symptoms.\n At one year, hybrid KTP/Nd:YAG laser treatment of the prostate was equivalent to TURP in the improvements in IPSS, maximum urinary flow rate and post-void residual urine.", "To compare the efficacy of standard transurethral electroresection of the prostate (TURP) and visual laser ablation in the treatment of benign prostatic hyperplasia (BPH).\n In a randomized prospective study, the prostate glands of 60 patients with symptomatic bladder outlet obstruction caused by BPH were treated with TURP or visual ablation with the Ultraline side-firing Nd:YAG laser; the patients were assessed using standard symptom scores, the measurement of residual urine and uroflowmetry both before and at 3 and 6 months after treatment.\n All patients in both treatment groups had a significant improvement in symptoms and objective measures of voiding. The laser treatment gave significantly better improvements in symptom score than did TURP (P = 0.034), but TURP produced significantly better peak urinary flow rates (P = 0.025).\n These early results indicate that laser ablation of BPH may be a good alternative in the surgical treatment of this disease.", "To compare the efficacy and safety of contact laser vaporization (CLV) of the prostate and transurethral resection of the prostate (TURP).\n Fifty patients with symptomatic prostatic hyperplasia with prostate volumes less than 40 ml were randomized to CLV or TURP treatment. All patients had infravesical obstruction confirmed preoperatively by pressure-flow studies.\n CLV lasted longer (51 +/- 13 min versus 34 +/- 12 min; p < 0.001), caused less bleeding (57 +/- 49 ml versus 175 +/- 133 ml; p < 0.001) and required longer bladder drainage time (4.3 +/- 6.1 versus 1.7 +/- 0.8 days; p < 0.01) than TURP. At 6-month follow-up, both treatments had improved objective urinary parameters and effectively reduced subjective symptoms. There were no significant differences between the study groups in symptoms scores (DanPSS-1), peak urinary flow rates (Qmax) and post-void residuals (PVR). Six months after treatment the detrusor pressure at peak urinary flow rate (PdetQmax) was 38.3 +/- 9.7 cm H2O in CLV patients and 31.3 +/- 9.9 cm H2O in TURP patients (NS). CLV treatment caused less retrograde ejaculation than TURP (1/16 potent CLV men versus 13/16 potent TURP men; p < 0.001).\n Contact laser prostatectomy proved to be a safe procedure which improved subjective and objective urinary parameters during 6-month follow-up as effectively as TURP in the treatment of symptomatic infravesical obstruction caused by minimal or moderate benign prostate enlargement.", "The aim of this study was to prospectively evaluate the safety and efficacy of contact laser ablation of the prostate (CLAP) vs. transurethral resection of the prostate (TURP) in symptomatic benign prostatic hypertrophy (BPH). During a 1-year period (1995-1996), 37 males 50 years of age or older were randomized to either CLAP using Nd:YAG laser treatment or TURP. Patients with Qmax <15 mL/s, American Urological Association (AUA) symptom score >12, and postvoid residual (PVR) >125 mL were enrolled. Patients were excluded if they had prior surgical treatment for BPH or known conditions that could affect bladder function. Comparisons of preoperative and postoperative symptom scores, Qmax, PVR, total catheter time, hospital stay, complications, and hematocrit changes were performed. A 2:1 randomization was used, which resulted in 26 CLAP and 12 TURP patients. One-year follow-up data were available for 21 CLAP and 7 TURP patients. The mean prostate volume, age, AUA symptom score, and Qmax were not significantly different between the two arms. Significant differences in favor of CLAP were shorter catheter time (27.2 vs. 40.4 hours; p < .05) and shorter hospital stays (28.5 vs. 60.0 hours; p < .05). The only other significant difference between the two arms was a lower AUA symptom score in favor of TURP at 1 year (4.7 vs. 8.4; p < .05). Qmax, PVR, and postoperative hematocrit were similar between the groups. The only complications included recatheterizations, which occurred more frequently in the TURP patients (25% vs. 14%). CLAP appears to be slightly less effective in AUA symptom score reduction; however, it is equally safe and is superior for shortening catheter time and hospital stay compared to TURP.", "The high-powered holmium:YAG laser can be used for incision, ablation and resection of the prostate. The technique of holmium laser resection of the prostate is compared to transurethral prostatic resection for surgical management of benign prostatic hyperplasia in this prospective randomized study.\n A total of 120 urodynamically obstructed cases were randomized to holmium laser or transurethral prostatic resection. All eligible patients were assessed preoperatively and at 3 weeks, and 3, 6 and 12 months postoperatively with an American Urological Association symptom score, peak urinary flow rate, and questionnaires concerning sexual function and continence. Preoperative pressure flow study, ultrasound prostate volume assessment and post-void residual volume measurement were repeated at the 6-month visit. All complications were noted.\n Holmium laser and transurethral resections resulted in significant improvements in symptom score, quality of life score, peak urinary flow rate and post-void residual urine measurements. Operating time was significantly longer in the holmium group but nursing contact time, catheter time and hospital stay were significantly less compared to the transurethral prostatic resection group. Urodynamic results were equivalent at 6 months. There were fewer side effects in the holmium group. Effects on continence, potency and symptoms were similar with 1-year followup.\n Holmium and transurethral resections of the prostate appear to be equivalent in surgical management of bladder outflow obstruction due to benign prostate hyperplasia. Perioperative morbidity was less in the holmium group.", "We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement.\n Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure.\n Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure.\n Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.", "To compare the efficacy and safety of hybrid laser treatment, i.e. the combination of visual Nd-YAG laser ablation of prostate and contact Nd-YAG laser vaporization of prostate, with transurethral resection of the prostate (TURP) in the treatment of patients with symptomatic bladder outlet obstruction secondary to a benign high-volume prostate.\n Forty-five symptomatic patients with hyperplastic prostates of >40 mL were randomized to undergo either hybrid laser treatment (21) or TURP (24). All patients were evaluated before and after treatment with a complex urodynamic assessment, and were accepted into the study only if they had infravesical obstruction in the pressure-flow study. In the hybrid method, Nd-YAG laser energy was first delivered by an 'adenoma-dependent' approach to all areas of the obstructing lateral lobe tissue through a side-firing gold-alloy tip fibre at 40 W for 90 s of 'burn'. The prostatic urethra was then opened and the median lobe vaporized using the a contact probe at 40 W. Patients were re-evaluated 3 and 6 months after treatment.\n Both treatments proved to be safe, and improved the subjective and objective outcome measures at 3 and 6 months compared with baseline values. After 3 months, there was a greater improvement in the TURP group in peak urinary flow rate (Qmax; P<0.01), mean urinary flow rate (Qave; P<0.01) and postvoid residual urine volume (P<0.05) than in the hybrid laser group. After 6 months, there was a greater improvement in the TURP group in detrusor pressure at Qmax (P<0.01), Qave (P<0.05) and prostate size (P<0.001) than in the hybrid laser group. In the pressure-flow study at 6 months, a higher proportion of patients (seven of 19) were still obstructed in the hybrid laser group than in TURP group (two of 21; P<0.05). TURP caused more intraoperative blood loss (P<0.001) and postoperative problems associated with bleeding; 38% of hybrid laser patients were discharged with a suprapubic catheter, whereas all TURP patients could urinate at discharge (P<0.01). The duration of bladder drainage was longer after hybrid laser treatment (P<0.001).\n The hybrid laser method was a safe but less effective treatment than TURP for benign prostatic enlargement in patients with prostates of >40 mL.", "To evaluate the safety and efficacy of holmium:YAG laser vaporization v transurethral electroresection (TURP) for benign prostatic hyperplasia.\n Thirty-six patients were randomized. Two laser procedures (60 to 80 W) were performed for one TURP. Symptom Score, peak flow rate, potency, and ejaculation status were measured at baseline and at 1, 3, 6, and 12 months.\n The mean operative time was 75 minutes for laser and 56 minutes for TURP (P = 0.0407). With a mean laser energy delivered of 103.6 kJ, hemostasis was satisfactory during vaporization. The mean catheterization time was 1.7 and 2.1 days in the laser and TURP group, respectively. For the laser and TURP groups, the mean AUA Score improved from 20 preoperatively to 7 and from 24.1 to 5, respectively, at 12 months. The mean peak flow increased from 8.4 to 19.5 mL/sec and from 7.6 to 16.8 ml/sec, respectively, at 12 months. These results are not statistically different. No significant initial dysuria occurred. No significant difference between the groups appeared in potency or ejaculatory status during the follow-up. One patient in the laser group (Day 5) and two in the TURP group (2nd and 6th month) had to undergo a second procedure to relieve obstruction.\n Although taking slightly longer to accomplish, holmium:YAG laser vaporization of BPH provides early results very similar to those of TURP with a shorter catheterization time and no initial dysuria or pain.", "We concluded a prospective randomised study comparing conventional electrocautery transurethral resection of the prostate (TURP) to laser prostatectomy using a right-angled Nd:YAG beam reflector. Seventy-one patients were evaluable, 34 laser and 37 TURP. Fifty patients have completed 6 months of follow-up. Using standard post prostatectomy outcome parameters of maximum flow rate and post void residual urine, laser prostatectomy shows equivalence at 6 months, with mean maximum flow rates of 8.76 ml/sec preoperatively improving to 15.47 ml/sec at 6 months, whilst for TURP patients, flow rates improved from a mean of 9.48 ml/sec preoperatively to 19.1 ml/sec at 6 months. Symptom scores remain higher for the laser patients at this time with a mean score of 9.27 compared to 4.43 for TURP patients. However, morbidity in the laser group is less, particularly given the absence of postoperative bleeding and the necessity for blood transfusion.", "To evaluate the sensitivity to change of outcome measures in a double-blind randomized controlled trial of transurethral resection of the prostate (TURP) and contact laser prostatectomy.\n A total of 152 patients were randomized to TURP or contact laser prostatectomy using the Surgical Laser Technology (SLT) system. Preoperative data were obtained using a self-administered questionnaire containing the American Urological Association (AUA-7) symptom score, the bothersome score (benign prostatic hyperplasia impact index), and the Short Form-36 health status questionnaire (SF-36). Follow-up was at 1 and 3 months. Effect size scores were calculated to indicate the extent of change from baseline to follow-up.\n Data were available on 148 patients: 72 received laser therapy and 76 received TURP. Mean change in AUA-7 score at 3 months was 7.3 in the laser arm, compared with 11.9 in the TURP arm (P < 0.05). Furthermore, substantial change was detected in both groups on the bothersome score. However, very few significant differences in SF-36 dimension scores from baseline to 3 months were detected.\n The SF-36 at both baseline and follow-up indicated a similar level of health status as that reported in the general population. Subsequently, the measure did not improve on any dimensions. Our data support the claim of some researchers that shorter disease-specific indices are vital to the evaluation of treatment regimens in clinical trials, especially when the general health of the patients is similar to that of the population.", "We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement.\n This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time.\n A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025).\n Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.", "Transurethral resection of the prostate (TURP) represents the accepted standard of surgical therapy for the management of symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH). However, this is a major operative procedure associated with significant perioperative morbidity. Visual laser ablation of the prostate (VLAP) utilizing a neodymium:yttrium-aluminum-garnet laser represents a new technologic approach to the surgical management of BPH. We compared the relative safety and efficacy of these two surgical approaches in a prospective, randomized trial.\n At 6 investigational sites in the United States, 115 men with symptomatic BPH more than 50 years of age and not in retention, were randomly assigned to undergo either TURP (59 patients) of VLAP (56 patients). VLAP patients received a mean of 10,200 J of energy delivered in a mean of 5.5 intraprostate laser applications. At preoperative baseline, 3 months, 6 months, and 1 year postoperatively, all patients underwent clinical evaluations, including ultrasonic prostatic volume determination, standardized American Urological Association (AUA)-6 symptom score, peak urine flow, postvoid residual urine volume, and quality-of-life assessment.\n Compared to TURP, the VLAP procedure required less time (23.4 versus 45.2 minutes; P < 0.01) and shorter hospitalization (1.8 versus 3.1 days, P < 0.01). VLAP was associated with a significantly lower rate of serious treatment-related complications compared to TURP (10.7% versus 35.6%; P < 0.01). Only One (2.2%) patient undergoing VLAP experienced a greater than 2.2 g/dL decrease in hemoglobin compared to 40% of TURP patients (P = 0.01). No patient in the VLAP group required blood transfusion compared with 3.4% of those undergoing TURP. Of the 115 patients, clinical outcomes measured at 1 year showed a mean improvement in AUA-6 symptom scores of -9.0 for VLAP compared with -13.3 for TURP (P < 0.04), mean increase in peak urinary flow rate of 5.3 cc/s for VLAP compared with 7.0 cc/s for TURP (P = 0.27), and mean decrease in postvoid residual urine volume of -55.4 cc for VLAP compared with -138.8 cc for TURP (P < 0.01). At 1 year, 78.2% of patients undergoing VLAP indicated that their quality of life was improved compared with 93.0% of patients undergoing TURP (P = 0.03). When compared with TURP, treatment of BPH with VLAP is associated with less hemoglobin decrease, a lower likelihood of serious complication, and requires less procedure time and a shorter hospital stay. Through a 1-year follow-up, VLAP produced significant improvement over baseline in objective and subjective outcome measures. However, for 1-year improvement in AUA-6 symptom score, postvoid residual urine volume, and quality of life, VLAP was less effective than TURP.\n In this initial study in the United States, with relatively low-energy laser applications, VLAP did not result in as complete a removal of prostatic tissue as did TURP. Considering the lower morbidity, shorter procedure and hospitalization times, and the degree of effectiveness that was achieved even at the low-energy doses used in this study, VLAP appears to be a viable and safe alternative to standard TURP.", "To compare the efficacy and frequency of complications of transurethral interstitial laser coagulation (ILC) and transurethral microwave thermotherapy (TUMT) with transurethral resection or incision of the prostate (TURP/TUIP) in patients with symptomatic benign prostatic hyperplasia (BPH).\n Forty-eight patients were randomized to undergo ILC, 46 to TUMT and 24 to TURP/TUIP; they were followed for 6 months and the outcome analysed on an intention-to-treat basis.\n At 6 months the symptom scores and maximum urinary flow rate (Qmax) had improved significantly in all groups. At 6 months the mean symptom score was 9.2 in both experimental groups and 6.8 in the control group (P > 0.05); the mean Qmax was 20.6 mL/s in the control group, 16.2 in the ILC group (P > 0.05 vs control) and 13.2 in the TUMT group (P < 0.05 vs. the control group). In the TUMT group patients developing urinary retention afterward had a significantly greater increase in Qmax than those who did not. The types of complications in the three groups varied. Urinary tract infection occurred frequently in the experimental groups, especially after ILC, whereas the 'well-known' complications of TURP occurred in the control group. Overall, 36% in the ILC, 54% in the TUMT and 73% in the control group had no complications (retrograde ejaculation excluded) during the first 6 months. One patient in the TUMT group underwent TURP after 3 months, whereas no patients in the ILC or the con-trol group were re-treated for BPH within the first 6 months.\n In the short term both ILC and TUMT are reasonable alternatives to standard transurethral surgery for symptomatic BPH, where the reduction of symptoms is the primary goal of treatment. However, both ILC and TUMT were associated with morbidity, although the complication profiles differed from those after TURP/TUIP. Both ILC and TUMT seem advantageous in some patients because of the reduced risk of bleeding and the eliminated risk of TUR syndrome, and because TUMT only requires local anaesthesia. Thus, as neither treatment is better in all aspects, the advantages of one technique over the other must be weighed when deciding how to treat each patient.", "A prospective randomized study comparing transurethral electrovaporization (TVP) vs laser ablation of the prostate was undertaken to compare the efficacy and safety of the procedures.\n A total of 31 patients underwent treatment, with 20 patients receiving electrovaporization surgery and 11 patients undergoing laser treatment. Patients underwent initial evaluation consisting of an American Urological Association (AUA) symptom score, prostate specific antigen (PSA), uroflowometry, pressure flow, and transrectal ultrasound for prostate volume. Patients were seen in follow-up at 1, 3 and 6 months.\n A total of 31 patients with a 2:1 randomization of TVP to laser treatment were enrolled. The laser patients had a mean pre-operative AUA symptom score of 19.0 and scores of 9.0, 6.0 and 5.0 at 1-, 3- and 6-month follow-up. The TVP patients had a mean pre-operative symptom score of 22.0 and scores of 7.0, 8.0 and 5.0 at 1-, 3- and 6-month follow-up. Mean peak uroflow (PF) rate pre-operative was 10.7 for the laser group and 7.7 for the TVP group. At 1-, 3- and 6-month follow-up, mean PF rates of 13.3, 17.6 and 16.5 were present for the laser patients and 15.0, 17.5 and 14.2 for the TVP group. The differences were not statistically significant. There were 6 complications in the laser patients and 7 complications in the TVP group. Operative time was a mean of 27 min for the laser patients and 46 min for the TVP group, and the difference in operative time was statistically significant.\n At 6-month follow-up the improvement in symptoms score and peak flow rate are comparable in both treatment groups. The electrovaporization procedure required significantly longer to perform than the laser procedure. Long-term follow-up is required to see if these results remain sustainable for electrovaporization therapy.", "To compare the safety and efficacy of laser ablation of the prostate, one of the minimally invasive treatments available for men with benign prostatic hyperplasia, to transurethral resection of the prostate (TURP).\n A prospective randomized study of 100 men with benign prostatic hyperplasia, with 50 patients in each treatment arm, was conducted. All patients met the entry criteria: age older than 45 years, no history of carcinoma of the prostate, a peak flow rate less than 15 mL/s, medical therapy failure, and the ability to undergo regional or general anesthesia. All patients underwent a preoperative evaluation consisting of the American Urological Association (AUA) symptom score, uroflowmetry, pressure-flow study, transrectal ultrasound for prostate volume, and serum prostate-specific antigen determination. Patients underwent either TURP or laser ablation of the prostate using the potassium titanyl phosphate (KTP)/neodymium: yttrium-aluminum-garnet laser. Patients were seen for follow-up at 1, 3, 6, and 12 months.\n The mean age was 68.2 years (range 45 to 90) for the laser group and 67.4 years (range 54 to 82) for the TURP group. The mean AUA symptom score was 22 for the laser group and 21 for the TURP group. The mean peak uroflow rate was 7.6 +/- 3.4 mL/s for the laser group and 6.5 +/- 4.0 mL/s for the TURP group. At 12 months of follow-up, the mean AUA symptom score had decreased to 7 (-69.5%) for the laser group and to 3 (-80.9%) for the TURP group. The mean peak uroflow rate increased to 15.4 mL/s (+ 107.8%) for the laser group and to 16.7 mL/s (+ 150.7%) for the TURP cohort. Seventy-five percent of the laser group had a 50% or greater decrease in their individual AUA symptom score compared with 93% of the TURP group. Sixty-five percent of the laser cohort had a 50% or greater increase in their peak uroflow rate compared with 75% of the TURP cohort.\n Laser prostatectomy produced improvements in the peak flow rate and symptom score similar to those produced by TURP. The patients who underwent laser treatment required a longer period to reach maximum improvement, which probably reflects the lack of tissue debulking at the time of surgery. Further improvement in laser technology will be required to produce more immediate results.", "To directly compare holmium laser resection of the prostate (HoLRP) with neodymium:yttrium-aluminum-garnet visual laser ablation of the prostate (VLAP), which represent two fundamentally different methods of laser prostatectomy.\n In a randomized, prospective comparison, a total of 44 men with symptomatic benign prostatic hyperplasia (BPH) were treated with either HoLRP or VLAP. Standard preoperative assessment included American Urological Association (AUA) symptom score, peak urinary flow rates (Qmax), ultrasound prostate volume, and residual urine measurements. Pressure-flow urodynamics were performed preoperatively and at 3 months postoperatively. Intraoperative and perioperative factors were assessed. The patients were followed at 1, 3, 6, and 12 months following the procedure.\n There were no significant differences between the patient groups for any preoperative parameter. The mean total operating time was longer in the HoLRP group (52 minutes) compared with the VLAP group (41 minutes) (P <0.01). The mean catheter times were 1.4 days (HoLRP) and 11.6 days (VLAP) (P <0.001). These times included the 9% of patients undergoing HoLRP and 36% of patients undergoing VLAP who required recatheterization. Immediate postoperative dysuria scores were higher in the VLAP group compared with the HoLRP group. There were no significant differences in AUA scores between the two treatment groups at any postoperative interval. The Qmax values were greater at follow-up in the HoLRP group, but statistical significance was not achieved at 12 months. However, both PdetQmax and Schäfer grade measurements taken at 3 months postoperatively were significantly lower in the patients undergoing HoLRP. Three patients (14%) required reoperation in the VLAP treatment arm but no patient who underwent HoLRP has required reoperation to date.\n HoLRP results in significantly improved patient outcomes compared to VLAP.", "To assess the safety and efficacy of endoscopic laser ablation of the prostate (ELAP), performed with the Urolase fiber and the neodymium:yttrium-aluminum-garnet laser, compared to transurethral resection of the prostate (TURP) in patients with bladder outflow obstruction secondary to benign prostatic hyperplasia (BPH).\n In this multicenter, prospective, randomized study, a total of 151 patients were treated (ELAP, 76; TURP, 75) of whom 137 completed 1 year follow-up (ELAP, 67; TURP, 70). Safety parameters included measurement of preoperative and 24-hour postoperative sodium, hematocrit, and hemoglobin values and careful monitoring of adverse events. Efficacy was assessed with the American Urological Association symptom score (6), urinary flow rates, and residual urinary volume measurements.\n There was 1 death in each group during the study period unrelated to the treatment procedure. There was a clinically significant improvement in all efficacy parameters in both groups. Between group comparisons favored TURP in maximum flow rate, residual urinary volume, and symptom score. ELAP had a better safety profile than TURP in the defined safety parameters of drop in hemoglobin and hematocrit values. In 16% of patients, a blood transfusion was required after TURP compared with no transfusions in the ELAP group. Urinary tract infections and dysuria were more frequent in the ELAP group.\n ELAP performed with the Urolase fiber is a useful alternative therapy to TURP in patients presenting with bladder outflow obstruction secondary to BPH." ]

[ "19787608", "19699531", "18286296", "20135139" ]

[ "Intravitreal injection of bevacizumab before vitrectomy for proliferative diabetic retinopathy.", "Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial.", "Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR).", "Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy." ]

[ "To evaluate the use of preoperative intravitreal bevacizumab (IVB) injection in patients undergoing pars plana vitrectomy for complications of proliferative diabetic retinopathy (PDR).\n In this prospective surgeon-masked randomized clinical trial, 40 eyes of 40 diabetic patients who were candidates for vitrectomy were randomly assigned to receive 2.5 mg IVB 3-5 days before operation (injected group) or no injection before operation (noninjected group). A preoperative complexity score (CS) was recorded. Best-corrected visual acuity, number of endodiathermy applications, backflush needle applications, duration of surgery, and postoperative vitreous hemorrhage were recorded.\n Twenty-two patients with a CS of 6+/-0.95 in the injected group and 18 patients with a CS of 5.7+/-1.1 in the noninjected group (p=0.3) were studied. Postoperative visual acuities were significantly better than preoperative visual acuities. Preoperative and 3-month postoperative visual acuities were the same for both groups; however, in the last follow-up examinations (mean 7+/- 3.6 months) the injected group had better visual acuities than the noninjected group (1.1+/-0.4 and 1.4+/-0.3 logMAR, respectively, p=0.006). Mean surgical time was 62+/-57.3 minutes in the injected group vs 95.5+/-36 minutes in the noninjected group (p=0.03): endodiathermy applications 6.0+/-4.3 vs 11.0+/-5.8 (p=0.004), backflush cannula applications 11.0+/-7.2 vs 18.1+/-7.8 (p=0.004). In non-silicone-filled eyes, no patient in the injected group developed significant postoperative vitreous hemorrhage obscuring the fundus details, while 7 eyes of noninjected eyes had this complication (p=0.01).\n IVB injection before vitrectomy for PDR facilitates the surgery, and may decrease the rate of postoperative vitreous hemorrhage and improve the visual acuity results of the operation.", "To evaluate the effect of preoperative intravitreal bevacizumab (IVB) injection on the rate of early (< or =4 weeks) postvitrectomy hemorrhage in patients with proliferative diabetic retinopathy (PDR).\n Prospective, randomized, double-masked clinical trial.\n Sixty-eight eyes of 68 patients undergoing pars plana vitrectomy for management of PDR complications.\n Eligible eyes were assigned randomly to 1 of 2 groups: the IVB group received 1.25 mg intravitreal bevacizumab 1 week before surgery, and the control group underwent a sham procedure.\n The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in best-corrected visual acuity (BCVA) and IVB-related adverse events.\n Of 68 eyes, 35 and 33 eyes were in the IVB and control groups, respectively. In the intention-to-treat analysis, the incidence of postvitrectomy hemorrhage 1 week and 1 month after surgery was significantly lower in the IVB group compared with the control group (P = 0.023 and P = 0.001, respectively). Mean BCVA improved from 1.88 logarithm of minimum angle of resolution (logMAR) units in both study groups before surgery to 0.91 logMAR units and 1.46 logMAR units 1 month after vitrectomy in the IVB and control groups, respectively (P = 0.001). Resolution of vitreous hemorrhage was observed in 9 eyes (25.7%) after IVB injection, obviating the need for vitrectomy; the corresponding figure was 2 eyes (6.1%) in the control group (P = 0.028). The per-protocol analysis included 16 eyes in the IVB group and 18 eyes in the control group; postvitrectomy hemorrhage occurred less frequently 1 week and 1 month after surgery in the IVB group compared with the control group (P = 0.033 and P = 0.003, respectively). Mean improvement in BCVA 1 month after vitrectomy was -1.05 logMAR units in the IVB group and -0.42 logMAR units in the control group (P = 0.004). No IVB-related complication was observed in the treatment group.\n Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. The need for vitrectomy also may be decreased significantly in these cases.", "To evaluate the use of preoperative intravitreal bevacizumab (IVB) in patients undergoing pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy (PDR).\n We studied 22 patients with severe PDR. A preoperative complexity score (CS) was recorded. Eleven eyes were treated with IVB, 1.25 mg, 5-7 days before PPV (group 1), and 11 eyes underwent direct PPV (group 2). Surgical time and intra-operative manoeuvres were recorded. Main outcome measure was feasibility of surgery, secondary goal was the visual and anatomic outcome at 6 months.\n The average CS was 5.5, and was similar in the two groups. Mean surgical time was 57 minutes in group 1 vs 83 minutes in group 2; mean tool exchanges was 27 vs 53, intraoperative bleeding 5 vs 15, endodiathermy 2 vs 9. No complications were recorded after IVB. Mean pre-operative BCVA was 1.87 logMAR in group 1 and logMAR 2.04 in group 2. Mean pre-operative BCVA was 1.87 logMAR in the bevacizumab group and 2.04 logMAR in group 2, not significantly different (p = 0.7). Mean post-operative BCVA at 6 months was 0.88 logMAR in group 1 and logMAR 2.01 in control group 2, significantly different (p = 0.01). Post-operative BVCA improved in bevacizumab group from pre-operative value (p = 0.15), while in control group there was non-significant increase (p = 0.96). Anatomical attachment was achieved in 11 patients in group 1 vs nine patients in group 2.\n IVB administered prior to vitrectomy was well tolerated and reduced active neovascularization, thus facilitating PPV.", "The purpose of this study is to evaluate the role, the safety and the effectiveness of intravitreal bevacizumab (IVB) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy (PDR).\n Case-Control Study\n Randomized controlled trial performed on 72 eyes of 68 patients affected by vitreous haemorrhage (VH) and tractional retinal detachment (TRD), which occurred as a consequence of active proliferative diabetic retinopathy (PDR). We randomly assigned eligible patients in a 1: 1: 1 ratio to receive a sham injection or an intravitreal injection of 1.25 mg of bevacizumab, either 7 or 20 days before the vitrectomy. In order to obtain three homogeneous groups of surgical complexity, we assigned to the following preoperative parameters a score from 0 to 3: a) vitreous haemorrhage, b) prior retinal laser-photocoagulation, c) morphological types of retinal detachment such as focal, hammock, central diffuse, table-top. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12, and 24 weeks after the surgery.\n Intraoperative management, safety, efficacy of IVB at different time injection as an adjunct to vitrectomy in the management of severe PDR RESULTS: Group A (sham injection): intraoperative bleeding occurred in 19 cases (79.1%), the use of endodiathermy was necessary in 13 patients (54.1%), relaxing retinotomy was performed on one patient (4.1%), and in four cases (16.6%) iatrogenic retinal breaks occurred. The surgical mean time was 84 minutes (SD 12 minutes). Group B (bevacizumab administered 7 days before vitrectomy): intraoperative bleeding occurred in two cases (8.3%) and the use of endodiathermy was necessary in two patients (8.3%). No iatrogenic breaks occurred during the surgery. The surgical mean time was 65 minutes (SD 18 minutes). Group C (bevacizumab administered 20 days before vitrectomy): intraoperative bleeding occurred in three cases (12.5%), the use of endodiathermy was necessary in three patients (1.5%), and an iatrogenic break occurred in one patient (4.1%) while the delamination of fibrovascular tissue was being performed. The surgical mean time was 69 minutes (SD 21 minutes). The average difference in the surgical time was statistically significant between group A and group B (p = 0.025), and between group A and group C (p = 0.031). At the end of the surgery, the retina was completely attached in all eyes. At the 6-month follow-up, we observed the development of tractional retinal detachment (TRD) in one out of 24 patients from group C (4%).\n A preoperative intravitreal injection of bevacizumab may represent a new strategy for the surgical treatment of severe PDR by reducing retinal and iris neovascularization: this would make surgery much easier and safer, thus improving the anatomical and functional prognosis. According to our study, the best surgical results are achieved performing the IVB 7 days preoperatively." ]

[ "16302629" ]

[ "Surgical treatment of thoracic outlet syndrome: a randomized trial comparing two operations." ]

[ "Various surgical approaches have been proposed for the treatment of thoracic outlet syndrome (TOS). The authors of this study focused on the differences in outcome after supraclavicular neuroplasty of brachial plexus (SNBP [no rib resection]) and transaxillary first rib resection (TFRR) in patients in whom the dominant clinical problem was pain.\n Fifty-five patients were randomized to undergo TFRR or SNBP. Patients with an anomalous cervical rib, intrinsic weakness, and primarily vascular findings were excluded from the study. Preoperatively, the following findings were typically observed: provocation of symptoms by certain postures (the so-called spear-throwing position as well as downward tugging of the shoulder) and marked tenderness in the supraclavicular fossa. The intergroup severity of the symptoms was comparable. Eight patients were lost to follow up. There were 24 TFRRs (in two cases the procedure was bilateral) and 25 SNBPs. The mean follow-up interval was 37 months. In both groups pain decreased significantly after surgery. By all measures the TFRR operation conferred superior results. Patients reported significantly less pain (39 +/- 7 compared with 61 +/- 7; score range 0-100 on a visual analog scale), greater percentage of pain relief (52 +/- 8% compared with 30 +/- 7%), and less pain (3.7 +/- 0.4 compared with 5.1 +/- 0.5) on an affective scale (all p < 0.05) in the TFRR and SNBP groups, respectively). In the TFRR group, 75% of patients reported good or excellent outcomes compared with 48% in the SNBP group (p < 0.05).\n Transaxillary first rib resection provided better relief of symptoms than SNBP. The major compressive element in patients with TOS-associated pain appeared to be the first rib." ]

[ "17280670", "9442174", "17071428", "5441273", "7059544", "17654188", "1547173", "7008940", "9091013", "8257472", "1998638", "8317528", "5023252" ]

[ "Amniotomy in labor.", "Dysfunctional labour: a randomised trial.", "The effect of amniotomy on the outcome of spontaneous labour in uncomplicated pregnancy.", "Effect of amniotomy upon labor. A controlled study.", "Spontaneous labour: when should the membranes be ruptured?", "A trial of amniotomy in a Palestinian hospital.", "Randomized trial of amniotomy in labour versus the intention to leave membranes intact until the second stage.", "Influence of spasmolytic treatment and amniotomy on delivery times: a factorial clinical trial.", "Randomised trial comparing a policy of early with selective amniotomy in uncomplicated labour at term.", "Effect of early amniotomy on the risk of dystocia in nulliparous women. The Canadian Early Amniotomy Study Group.", "A randomized controlled trial of early amniotomy.", "The influence of elective amniotomy on fetal heart rate patterns and the course of labor in term patients: a randomized study.", "Amniotomy during the active phase of labor." ]

[ "nan", "Sixty-one women making slow progress in the active phase of spontaneous labour with intact membranes were randomised to oxytocin and amniotomy, amniotomy only or expectant management. The data show that oxytocin significantly increases the rate of cervical dilatation and shortens prolonged labour, when compared with amniotomy alone and expectant management (P = 0.0144 and 0.0006, respectively). The impact on the operative delivery rate and neonatal outcome is difficult to assess due to the small number of relevant adverse outcomes. Women reported higher satisfaction score in the two groups where intervention followed the diagnosis of dysfunctional labour.", "The objective of this study is to determine the effect of amniotomy on the outcome of spontaneous labour in uncomplicated pregnancy. A prospective randomised study of low-risk parous women with spontaneous onset of labour at term with singleton fetus in cephalic presentation and intact amniotic membranes and a cervical dilatation between 4 and 5 cm were randomly assigned to have amniotomy (Case) or no amniotomy (Control) during the course of labour. Maternal demographics, labour-delivery data and newborn outcome were compared. A total of 128 women were studied. The duration of labour was significantly shorter in the amniotomy group than the control group (208 vs 292 min; p < 0.05) with the only difference being in the first stage of labour. There was however no difference on the oxytocin requirement for labour augmentation, caesarean section rate, incidence of suspected fetal distress or instrumental delivery in both groups. Newborn outcome measured by Apgar scores at 1 and 5 min showed no significant difference. In conclusion, amniotomy significantly reduced the duration of the first stage of labour without affecting the oxytocin requirement, the rate of caesarean section and newborn outcome.", "nan", "Sixty-eight patients (32 multigravidae, 36 primigravidae) with intact membranes admitted in early spontaneous labour were studied. Patients were randomly allocated to two groups: group I had an immediate amniotomy and group II were allowed to retain their membranes intact until full dilatation. Early amniotomy significantly shortened the length of labour and reduced the need for augmentation and instrumental delivery. There were no differences between the two groups in fetal outcome as measured by Apgar scores, umbilical arterial and venous blood pH, neonatal jaundice or admission to the special-care baby unit. Fetal heart-rate recordings obtained in group I by applying a fetal electrode after amniotomy were of superior quality to those obtained in group II by ultrasound and were more suitable for interpretation. 'Normal' and 'suspicious' tracings occurred equally in the two groups. Our results suggest some benefits from early amniotomy and no adverse effects on the fetus.", "This randomised controlled trial of routine amniotomy was carried out in a developing country setting to investigate the effect of this common procedure on the duration of labour, intra-partum interventions and selected newborn and maternal outcomes. In a Jerusalem teaching hospital, 533 multiparous and 157 nulliparous low-risk women were randomised to either amniotomy or intent to conserve membranes. For multiparae, the median duration from randomisation to full dilatation was 95 and 160 min, respectively in the intervention and control arms (p < 0.001); for nulliparae it was 210 and 270 min, respectively (p < 0.001). In both groups, oxytocin was used less in the intervention arms (p < 0.001), and no difference in mode of delivery and immediate outcomes was detected. However, given the risks of this intervention and these study findings indicating an overall short duration of childbirth, amniotomy should be limited to cases of abnormal progress of labour.", "To compare by randomized prospective clinical trial the outcome of labours which are managed with the intention to leave the membranes intact, compared with the practice of elective artificial rupture of the membranes (ARM) in early established labour.\n Prospective randomized controlled trial of low risk women admitted in spontaneous labour, with intact membranes.\n The labour ward of St. James's University Hospital, Leeds, UK.\n 362 women in spontaneous labour with intact membranes and no evidence of fetal distress, between 37 and 42 weeks gestation. During the course of the trial it was found that some randomization cards could not be accounted for and a system of daily checks was instituted. The results were analysed for all recorded women (n = 362) and after institution of the more rigorous system (n = 120).\n The duration of each phase of labour, epidural rate, prevalence of an abnormal cardiotocograph (CTG) (assessed blind), method of delivery and neonatal outcome.\n 178 of the 183 women (97%) in the ARM group had their membranes ruptured in early labour, and 83 (46%) of the 179 women allocated to non-intervention had ARM performed at some stage. A significant decrease in the duration of labour (mean 8.3, SD 4.1 h vs mean 9.7, SD 4.8 h, n = 156; P = 0.05) was found amongst primigravidae allocated to ARM when compared with non intervention. The duration of the second stage of labour was unaffected. In the ARM group the epidural rate was higher and labour was more often complicated by CTG abnormalities. There were no differences in the method of delivery, fetal condition at birth (cord blood lactate, Apgar score) or postpartum pyrexia between the ARM and non-intervention groups. The same trends were observed when analysis was confined to women entered into the trial after the system of rigour was instituted.\n Routine ARM results in labour that is slightly shorter than if the membranes are allowed to rupture spontaneously but more epidurals are used suggesting that labour is more painful. There are fewer fetal heart rate abnormalities if the membranes are left intact but amniotomy has no effect on fetal condition at birth.", "In a double-blind factorial clinical trial in 300 patients (150 primiparae and 150 multiparae), the effects of amniotomy, rociverine, and butylscopolamine bromide administration on the course of labor were investigated. Rociverine significantly reduced the dilatation time and had no effect on the delivery time. Butylscopolamine bromide had no appreciable effect on the dilatation and expulsion times. Amniotomy resulted in a lengthening of the dilatation time and no significant change in the expulsion time.", "To compare two management policies: rupture of the fetal membranes when women are in normal labour or leave them intact as long as feasible.\n The labour ward of a city university hospital.\n Automated randomised clinical trial.\n 1540 women in uncomplicated term labour. Data on labour duration, blood loss, oxytocin use and fetal condition were collected from 1132 women. Some data from nulliparous women has been presented earlier by the UK Amniotomy Group.\n Duration of labour, Apgar score, fetal morbidity and maternal morbidity including perineal injury, mode of delivery, epidural rates and the total number of vaginal examinations in the first stage of labour after amniotomy.\n Amniotomy at the next vaginal examination or amniotomy only if indicated. The median cervical dilatation at membrane rupture was 2 cm greater in the first group.\n A policy of routine amniotomy in labour had no measurable advantage over selective amniotomy for parous women (difference = 4 min) but shortened labour in nulliparous women by 1 h (Mann-Whitney U test: P < 0.05). There was a suggestion of a higher caesarean section rate (OR 1.9; 95% CI 0.9-3.5), and there were more vaginal examinations after membrane rupture in the group allocated routine amniotomy. There were no measurable differences in oxytocin use, fetal condition at birth, retained placenta rates, blood loss, pain or analgesia requirements.\n Routine amniotomy may shorten the first labour but not subsequent ones. There is a suggestion that routine surgical interference may be harmful by increasing the risk of caesarean section, and this agrees with data from other trials (common odds ratio 1.2; 95% CI 0.92-1.6).", "Early amniotomy has been advocated as a means of preventing dystocia, but its efficacy has not been studied prospectively. The purpose of this multicenter study was to determine whether routine early amniotomy reduces the risk of dystocia for nulliparous women in spontaneous labor.\n We studied 925 nulliparous women in labor, who were stratified according to the degree of cervical dilatation (< 3 cm vs. > or = 3 cm) and randomly assigned to either early rupture of the membranes (amniotomy group) or conservative management of labor (conservative-management group). Dystocia was defined as a period of at least four hours after dilatation of the cervix to 3 cm had been reached during which the mean rate of cervical dilatation was less than 0.5 cm per hour.\n Dystocia was significantly less frequent in the amniotomy group than in the conservative-management group (34 percent vs. 45 percent; relative risk, 0.8; 95 percent confidence interval, 0.6 to 0.9). The median length of time from randomization to full dilatation was 136 minutes shorter in the amniotomy group, and there was a trend toward less frequent use of oxytocin among the women assigned to amniotomy (36 percent vs. 41 percent; relative risk, 0.9; 95 percent confidence interval, 0.8 to 1.0). In a stratified analysis, the frequency of dystocia associated with amniotomy was reduced only among women with > or = 3 cm initial dilatation. The cesarean-section rate was similar in the two groups (amniotomy, 12 percent; conservative management, 11 percent). There were no statistically significant differences in outcome between the infants delivered by the women in the two groups; the measures of an adverse outcome included admission to a neonatal intensive care unit, five-minute Apgar score below 7, and arterial cord-blood pH below 7.2.\n Early amniotomy is an effective method of shortening the duration of labor and reducing the frequency of dystocia among nulliparous women in labor, but it does not lower the rate of cesarean section.", "OBJECTIVE-To determine if a policy of early amniotomy resulted in a reduction in mean labour duration when compared to a policy of conservation of the membranes. DESIGN-A single-centre randomized controlled trial. SETTING-A tertiary care teaching hospital in Alberta, Canada. SUBJECTS-Ninety-seven term nulliparae in spontaneous labour, baby in cephalic presentation. INTERVENTION-Early amniotomy versus intent to keep membranes intact. MAIN OUTCOME MEASURES-Interval from randomization to delivery, rate of abnormalities of fetal heart rate tracings, cord artery blood pH, Apgar scores. RESULTS-The mean interval from randomization to delivery was 390.9 (SE 29.1) min in the amniotomy group and 442.9 (SE 34.1) min in the control group (P = 0.251). There were no differences between groups in the occurrence of fetal heart rate tracing abnormalities, nor was there a difference in the proportion of babies with abnormal Apgar scores, or abnormal cord pH (less than 7.20). CONCLUSION-The results of the study fail to support the long held belief that early amniotomy is an effective method for reducing labour duration.", "Our study was designed to evaluate the effects of routine elective amniotomy on the frequency and severity of abnormal fetal heart rate patterns and on the course of labor and the need for oxytocin augmentation.\n A randomized, controlled trial was conducted at term in patients in active labor who were randomly selected to undergo elective amniotomy (amniotomy group) or left intact with amniotomy reserved for specific indications (intact group).\n Four hundred fifty-nine patients were studied (235 in the amniotomy group vs 224 in the intact group). Average cervical dilatation at rupture was 5.5 cm in the amniotomy group and 8.1 cm in the intact group. Analysis of fetal heart rate revealed more mild and moderate variable decelerations in the active phase of labor in the amniotomy group but no difference in the frequency of more severe decelerations or operative deliveries. In the intact group the need for oxytocin was twice as common (76 in the intact group vs 36 in the amniotomy group, p = 0.000005), and the active phase of labor was considerably longer (5 hours 56 minutes in the intact group vs 4 hours 35 minutes in the amniotomy group). Neonatal outcome was similar in the two groups.\n Elective amniotomy appears to increase the likelihood of umbilical cord compression in the active phase of labor and results in more mild and moderate variable decelerations, but it does not result in more severe abnormal fetal heart rate patterns or more operative intervention. Elective amniotomy does, however, shorten the active phase of labor and decreases the need for oxytocin augmentation.", "nan" ]

[ "3890463", "3535823", "8123509", "2284579", "9458563", "12081124", "9836156", "3277760", "3920561", "3643399", "11803175", "10048612", "319653", "7030227", "6993111", "12166794", "448492" ]

[ "Bacterial colonization and neonatal infections. Effects of skin and umbilical disinfection in the nursery.", "Does routine newborn bathing reduce Staphylococcus aureus colonization rates? A randomized controlled trial.", "Midwifery: umbilical cord care in pre-term babies.", "Hydrophobic material in routine umbilical cord care and prevention of infections in newborn infants.", "Cleaning solutions and bacterial colonization in promoting healing and early separation of the umbilical cord in healthy newborns.", "Antiseptics for preventing omphalitis.", "Alcohol versus natural drying for newborn cord care.", "Randomized study of six umbilical cord care regimens. Comparing length of attachment, microbial control, and satisfaction.", "The effect of isopropyl alcohol and triple dye on umbilical cord separation time.", "Treatment of umbilical cords: a randomised trial to assess the effect of treatment methods on the work of midwives.", "Umbilical cord care: the effect of eight different cord-care regimens on cord separation time and other outcomes.", "The effectiveness of single and multiple applications of triple dye on umbilical cord separation time.", "Group B beta-hemolytic streptococcal colonization. Acquisition, persistence, and effect of umbilical cord treatment with triple dye.", "Umbilical care and cord separation.", "Effect of antiseptic cord care on bacterial colonization in the newborn infant.", "Randomized trial of alcohol versus triple dye for umbilical cord care.", "Brief clinical and laboratory observations." ]

[ "In a prospective randomized study different regimens for skin and umbilical disinfection in newborn infants were tested: daily whole body soap wash (control group), daily whole body soap wash and umbilical cleansing with (i) benzine solution, or (ii) 0.05% chlorhexidine, and daily whole body wash and umbilical cleansing with a 4% chlorhexidine detergent solution (Hibiscrub). Bacterial cultures were taken from the nose and umbilical area at discharge. Clinical infections were registered in the nursery, and after discharge until 6 weeks of age. Cultures were taken from infected areas. In the control group a high colonization rate was found for S. aureus (91%), E. coli (39%), and group B streptococci (GBS) (20%). The colonization rates were influenced by the Hibiscrub regimen (colonization rate for S. aureus 59%, E. coli 23%, and GBS 10%), but not by the other regimens. Infections (pemphigus, paronychia, conjunctivitis, umbilical infection) occurred in 12.9% of the infants, of whom 65% got infection after discharge from the nursery. 96% of the infections were caused by S. aureus, and 87% caused by strains colonizing the infants in the nursery. None of the tested regimens reduced the rate of infections during the first 6 weeks of life.", "nan", "A trial was undertaken to investigate infection rates and to measure cord separation time under four different cord care regimes in pre-term babies within the Neonatal Unit of Ninewells Hospital, Dundee. The evidence of the trial suggests that the present method of treating umbilical cords in pre-term babies with Sterets and Ster-zac powder is sound. More importantly, there is good evidence that a policy of leaving umbilical cords untreated cannot be recommended as safe practice within the unit. It is noted that the numbers in this trial (about 100) were not large, but the trial did run for a full year. Any further trials would need to be multicentered to obtain a larger sample set in a reasonable amount of time.", "In a prospective randomized study 2 different regimens for umbilical disinfection in newborn infants were tested: (i) a bandage of hydrophobic material (Sorbact; n = 1,213), and (ii) daily cleansing with 0.5% chlorhexidine in 70% ethanol (n = 1,228). Infections were registered in the nursery as well as after discharge until 6 weeks of age, and bacterial cultures taken from infected areas. A total of 410 infections were registered in 377 (15.4%) of the 2,441 infants. Total infection rates of 16.3 and 14.6% were found in the hydrophobic material group and the chlorhexidine-ethanol group respectively (p greater than 0.05). No differences were found between the groups in infection rates in the nursery (8.9 vs. 8.7%), after discharge (7.4 vs. 5.9%), or in rates of different types of infections (conjunctivitis, pyoderma, paronychia, omphalitis) (p greater than 0.05). 536 strains were isolated. 498 (92.9%) were gram-positive, 45 (8.4%) gram-negative, and 7 (1.3%) candida strains. 229 (55.9%) were Staphylococcus aureus strains. No differences were found between the two groups concerning distribution of the different strains isolated. Separation of the umbilical cord occurred significantly later in the hydrophobic material group than in the chlorhexidine-ethanol group (6.2 +/- 2.2 vs. 5.8 +/- 2.1 days; p less than 0.05). Hydrophobic material does not prevent infections more effectively compared to 0.5% chlorhexidine in 70% alcohol.", "The efficacy of alcohol or water in promoting umbilical cord separation was compared in a randomized controlled trial. Rates of skin colonization between groups were also evaluated on three occasions. Time to cord separation, rates of colonization, and species of organisms that colonized were compared between groups. Of 148 participants, 136 (92%) completed the protocol. Cords that were cleaned with sterile water separated more quickly than those cleaned with alcohol (t = 3.15, p = 0.002). Between-group differences in colonization rates were not found (F = 1.59, df = 2, p = 0.205). Umbilical or other infections did not occur. Bacterial colonization of the umbilical area and surrounding skin occurs over time in healthy term neonates. Cleaning with alcohol will increase the length of time from birth to cord separation but will not prevent colonization of the umbilical area.", "Omphalitis may cause serious complications and contribute to neonatal morbidity and mortality. From January 1997 to August 1998, the incidence of omphalitis in the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital had been increased from 0.9 to 17.4 per 1,000 live births. A prospective randomized trial using antiseptic applied directly to the umbilical stump was conducted aiming to reduce an epidemic outbreak of omphalitis in the newborn nursery.\n To determine which antiseptic is appropriate for preventing omphalitis in the newborn infants.\n Newborn infants delivered in the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital were randomized into group A (Triple dye) or group B (70% Alcohol). The infant with omphalitis was assessed by a pediatrician or a neonatology fellow. At home, the same antiseptic will be continually applied to the umbilical stump daily until a few days after cord detachment. Relative risk was calculated and statistical significance was tested by Chi-square test.\n Four hundred and twenty-seven infants were enrolled. Birth weight, gestational age and gender of the infants in both groups were not different. There were no known maternal risk factors for omphalitis. Omphalitis was observed in 9/213 (4.2%) infants in group A and 23/214 (10.7%) infants in group B. The relative incidence rate between each group was statistically significant (p<0.01). Triple dye group was 60 per cent less likely to develop omphalitis compared to 70 per cent Alcohol group (RR 0.39, 95% CI: 0.19-0.83). The mean duration for cord detachment were 13.6 and 11.5 days in group A and group B, respectively.\n During an epidemic outbreak of omphalitis, Triple dye was the most appropriate and effective antiseptic to prevent omphalitis but could delay cord separation.", "To compare alcohol cleaning and natural drying of newborn umbilical cords.\n Prospective, randomized controlled trial.\n Tertiary-level university teaching hospital and level II community hospital.\n Of 1,876 singleton full-term newborns enrolled, 1,811 completed the study.\n Newborns, from birth until separation of the cord, were randomized to either (a) umbilical cleansing with 70% isopropyl alcohol at each diaper change or (b) natural drying of the umbilical site without special treatment.\n Umbilical infection, cord separation time, maternal comfort, and cost.\n No newborn in either group developed a cord infection. Primary care providers obtained cultures for cord concerns in 32 newborns (1.8%), with colonization for normal flora, Staphylococcus aureus, and Group B streptococcus proportionately equal in alcohol and air dry groups. Cord separation time was statistically significantly different (alcohol group, 9.8 days; natural drying group, 8.16 days; t = 8.9, p = < .001). Mothers described similar comfort with cord care and relief with cord separation. Costs of alcohol drying while in the hospital were greater than those of natural drying.\n (a) Evidence does not support continued use of alcohol for newborn cord care; (b) health care providers should explain the normal process of cord separation, including appearance and possible odor; and (c) health care providers should continue to develop evidence to support or eliminate historic practices.", "Two hundred and seventy one infants were enrolled in a study to compare six different methods of treating the umbilical cord. Antimicrobial control was equal for all methods. Repeated triple dye application was considered least acceptable by staff and parents and had the longest attachment time. Povidone-iodine was associated with the shortest attachment time and was most liked. If there is no special need to treat a specific nosocomial outbreak, duration of cord attachment and satisfaction of staff and parents can help clinicians decide on a cord care regimen.", "nan", "nan", "In this study we evaluate the effect of eight cord-care regimens on cord separation time and other secondary outcomes: omphalitis, sepsis, death, cord bleeding, compliance, satisfaction or dissatisfaction with regard to the type of treatment, umbilical cord colonization--in 1,535 healthy term infants. The eight cord-care regimens studied were: 70% alcohol, natural drying, salicylic sugar powder, triple dye, micronized green clay powder, colloid silver-benzyl-peroxide powder, neomycin-bacitracin powder, 1% basic fuchsine. None of the newborns developed sepsis or died and we found only sporadic cases of omphalitis. With regard to cord separation time the best results were obtained with salicylic sugar powder (5.6 +/- 2.3 days) and green clay powder (6.7 +/- 2.2 days). Both forms of treatment proved to be more effective (p < 0.05) than all the others. We found that salicylic sugar powder allows for early cord detachment resulting in excellent parent treatment compliance and reduction of their concern, notwithstanding higher percentages of cord bleeding. The rate of positive umbilical swabs was low and was significantly higher only than the results obtained with neomycin-bacitracin powder treatment. This study demonstrates that, in hospital nurseries of developed countries, salicylic sugar powder can be effectively and safely used for umbilical cord care of healthy term infants.\n Copyright 2002 S. Karger AG, Basel", "The effectiveness of single and multiple applications of triple dye for umbilical cord care in the umbilical cord separation time (UCST) was evaluated in 180 neonates. Seven neonates were excluded, three where the cord stump separation time was uncertain and four to whom contact was lost. The participating neonates were randomly assigned to two groups. Group 1, 101 neonates, were treated with a regimen of a single application of triple dye. Group 2, 79 neonates, were treated with multiple applications of triple dye. Complete information was obtained from 97 neonates (96.2%) in group 1 and 76 (96%) in group 2. The UCST was 12.6 +/- 0.45 (mean +/- SE) days in group 1 and 16.68 +/- 0.65 days in group 2 (P < 0.0001) and showed no significant association with infants' gender, mode of delivery, gravidity, gestational age, birth weight, or hospital stay.\n A single application of triple dye may be a more favourable regimen with a similarly antimicrobial effect, a shorter UCST and may be more cost effective than multiple applications of triple dye in umbilical cord care.", "Following an outbreak of group B beta-hemolytic streptococcal neonatal infection (GBS), a prevalence survey of GBS colonization was performed on 238 infants. No important differences were noted in the prevalence of colonization when the infants were grouped according to age. Follow-up of 24 colonized babies for three months disclosed that most had persistence of GBS at the rectum and pharynx. Local umbilical cord care with triple dye (TD) or hexachlorophene skin cleanser was compared with untreated controls with respect to rates of GBS colonization. At birth the colonization rates of the three groups were similar. The rate of acquisition of colonization with GBS was 1.0% in the TD group, 6.3% in the hexachlorophene group, and 8.3% in the control group. Triple dye was much more effective than no specific cord care or hexachlorophene in preventing acquisition of GBS colonization.", "Four different treatments for the care of the umbilical cord were compared in a randomised, controlled study. Triple dye was associated with a significantly earlier separation of the cord than either 1% neomycin or 1% silver sulphadiazine ointment, and it was nearly as effective as bismuth subgallate (an astringent powder) in causing rapid sloughing. If the mother is made aware that care of the umbilical cord may delay cord separation she may be spared unnecessary concern.", "A randomized controlled study was undertaken to compare the effectiveness of three umbilical cord treatment regimens in controlling neonatal bacterial colonization. The regimens studied included daily application of castile soap, triple dye and silver sulfadiazine. The triple dye and silver sulfadiazine regimens inhibited bacterial colonization. Staphylococcal colonization was inhibited most effectively by triple dye treatment. Group B streptococcal colonization was equally inhibited by triple dye and silver sulfadiazine. Silver sulfadiazine was more effective in controlling colonization with gram-negative microorganisms.", "Over a 4-month period, all infants admitted to the well-baby nursery were enrolled in a prospective study designed to compare cord separation times between infants treated with triple dye once, followed by daily alcohol application, to infants treated with daily alcohol application alone. Follow-up phone calls were done 7 days after discharge, with weekly calls until cord separation occurred. The objective was to determine whether the umbilical cord care regimen of triple dye followed by alcohol has an advantage over the alternative regimen of alcohol alone, with regard to cord separation, parenting, or healthcare caretaker preferences. In total, 634 infants were enrolled, with 599 infants (94%) completing the study. Infants in the alcohol alone group had a shorter cord separation time by 3 days (10 versus 13 days) (p < 0.0001). There was no reported increase in infection, and monetary savings were noted. We conclude that alcohol applied once a day appears to be a safe and effective means of promoting cord detachment.", "nan" ]

[ "12397739", "9876076", "10688215", "8165534", "16076330", "10512946", "12727169", "1306666", "8619455" ]

[ "The value of contrast radiology for postoperative adhesive small bowel obstruction.", "Water-soluble contrast study predicts the need for early surgery in adhesive small bowel obstruction.", "Upper gastrointestinal contrast study in the management of small bowel obstruction--a prospective randomised study.", "Therapeutic effect of oral Gastrografin in adhesive, partial small-bowel obstruction: a prospective randomized trial.", "Randomized controlled trial of Gastrografin in adhesive small bowel obstruction.", "Oral urografin in postoperative small bowel obstruction.", "Small bowel obstruction--the water-soluble follow-through revisited.", "The value of water-soluble contrast radiology in the management of acute small bowel obstruction.", "Water-soluble contrast material has no therapeutic effect on postoperative small-bowel obstruction: results of a prospective, randomized clinical trial." ]

[ "Contrast radiology predicts the outcome of treatment for patients with small bowel obstruction. The optimal method of contrast radiology to determine the indications for and timing of surgery is controversial.\n Contrast radiology was performed for patients with postoperative adhesive small bowel obstruction between April 1, 2000 and March 31, 2001. Nearly 40 mL of gastrografin mixed with 40 mL of water was administered either orally or via a nasogastric tube to each patient within 24 hours of hospital admission. Serial erect and supine plain abdominal radiographs were taken 4, 8, 16 and 24 hour later.\n Of 107 patients with postoperative adhesive small bowel obstruction, 97 patients had the examination completed. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of this study as an indicator for non-operative treatment were 98.9%, 66.6%, 96.9%, 97.8% and 80%. However, contrast radiology had little impact on the diagnosis of 6 patients with strangulated small bowel obstruction. Ninety-two of 93 patients (98.9%) who were resolved with non-operative treatment were resolved within 48 hours of hospitalization.\n Contrast radiology should be considered for patients with simple small bowel obstruction who did not improve with non-operative measures after 48 hours of hospitalization.", "The optimal period of conservative treatment for adhesive small bowel obstruction remains controversial. This study sought to determine whether a 24-h abdominal radiograph after oral Urografin is a reliable indicator for operation in patients with adhesive small bowel obstruction.\n One hundred and sixty-one patients who suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene underwent a Urografin study. Some 40 ml Urografin mixed with 40 ml distilled water was administered either orally or via a nasogastric tube to each patient. Serial plain abdominal radiographs were taken 4, 8, 16 and 24 h later. If an earlier plain radiograph showed that contrast medium had reached the ascending colon, subsequent radiographs were not taken.\n Contrast medium reached the colon within 24 h in 112 patients (70 per cent). These patients were all treated successfully with non-operative methods. Contrast medium was not observed in the colon within the first 24 h in 49 patients (30 per cent). Operation was performed in 47 of these patients and non-operative treatment was given in two. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of Urografin reaching the colon within 24 h as an indicator for non-operative treatment were 98, 100, 99, 100 and 96 per cent respectively.\n All patients with evidence of Urografin reaching the colon within 24 h were treated successfully with non-operative methods. The results of this prospective study suggest that patients with adhesive intestinal obstruction in whom contrast medium fails to reach the colon within 24 h should receive prompt surgical intervention.", "To find out whether contrast radiography helps to resolve small bowel obstruction.\n Prospective randomised trial.\n University hospital, Norway.\n 98 consecutive patients with symptoms of small bowel obstruction and a plain abdominal radiograph that confirmed the diagnosis.\n The patients were randomly allocated to receive a mixture of barium and sodium diatrizoate (Gastrografin) (n = 48) or not (n = 50). Both groups were followed up clinically and by repeated abdominal films.\n Non-operative resolution of small bowel obstruction; number of patients with strangulated bowel; bowel resections; mortality; complications; hospital stay; and time from admission to operation.\n No significant differences were observed between the groups in the incidence of non-operative resolution (31/48 in contrast group, 35/50 in control group, OR: 0.89), strangulation obstruction (1/48 in contrast group, 4/50 in control group, OR: 0.24), bowel resection (3/48 in contrast group, 4/50 in control group, OR: 0.76), complications (8/48 in contrast group, 5/50 in control group, OR: 1.80), mortality (3/48 in contrast group, 1/50 in control group, OR: 3.26), and hospital stay (0-7 days: 34/48 in contrast group, 38/50 in control group, p = 0.95). The contrast group had a shorter interval between admission and operation than the control group (0-24 hours: 12/48 in contrast group, 3/50 in control group, p = 0.005).\n The contrast examination did not contribute to the resolution of small bowel obstruction.", "Previous published clinical observations claim that Gastrografin, a hyperosmolar gastrointestinal water-soluble contrast agent, speeds the resolution of postoperative ileus, barium impaction ileus, adhesive small-bowel obstruction, and intestinal obstruction caused by parasites and bezoars. However, no objective data exist that support the therapeutic effects of Gastrografin in these situations.\n A total of 107 episodes of adhesive, partial small-bowel obstruction in 99 patients were randomized into a control group (48 episodes), who were treated with conventional methods, and a trial group (59 episodes), who were treated with 100 ml of Gastrografin administered through the nasogastric tube. The following variables were examined: time to resolution of partial small-bowel obstruction, the need for operation, complications, and hospital stay.\n Mean timing of the first stool was 23.3 hours in the control group and 6.2 hours in the patients receiving Gastrografin (p < 0.00001). Ten obstructive episodes (21%) in the control group required operative treatment compared with six (10%) in the trial group (p = 0.12). Mean hospital stay for the patients who responded to conservative treatment was 4.4 days and 2.2 days in the control and trial groups, respectively (p < 0.00001). One patient in each group died after operation. No Gastrografin-related complications were observed.\n Orally administered Gastrografin is safe and has a therapeutic role in adhesive, partial small-bowel obstruction. It significantly prompts the resolution of the obstructive episodes and shortens hospital stay. However, further studies are necessary to confirm the significance of our observation that it may reduce the need for operation.", "Several previous studies have shown that Gastrografin can be utilized to triage patients with adhesive small bowel obstruction (ASBO) to an operative or a non-operative course. Previous studies assessing the therapeutic effect of Gastrografin have been confounded by post-administration radiology alerting the physician to the treatment group of the patient. Therefore the aim of the present paper was to test the hypothesis that Gastrografin hastens the non-operative resolution of (ASBO).\n Patients, diagnosed with ASBO on clinical and radiological grounds, were randomized to receive Gastrografin or placebo in a double-blinded fashion. Patients did not undergo further radiological investigation. If the patient required subsequent radiological intervention or surgical intervention they were excluded from the study. End-points were passage of time to resolution of ASBO (flatus and bowel motion), length of hospital stay and complications.\n Forty-five patients with ASBO were randomized to receive either Gastrografin or placebo. Two patients were excluded due to protocol violations. Four patients in each group required surgery. Eighteen of the remaining patients received Gastrografin and 17 received placebo. Patients who received Gastrografin had complete resolution of their ASBO significantly earlier than placebo patients (12 vs 21 h, P = 0.009) and this translated into a median of a 1-day saving in time in hospital (3 vs 4 days, P = 0.03).\n Gastrografin accelerates resolution of ASBO by a specific therapeutic effect.", "The aim of our study was to determine whether Urografin has the potential to offer surgeons a way of differentiating complete from partial small bowel obstruction and whether partial small bowel obstruction can be treated nonoperatively. Altogether 116 patients who had postoperative small bowel obstructions without any toxic signs underwent Urografin studies. Urografin (40 ml) mixed with 40 ml of distilled water was administrated either orally or via nasogastric tube to each patient. Serial plain abdominal radiographs were taken 2, 4, and 8 hours later. A total of 74 patients (63.8%) whose contrast medium reached the colon within the first 8 hours were considered to have partial obstruction and were successfully treated with intravenous hydration and nasogastric decompression. The remaining 42 patients (36.2%) in whom the contrast medium failed to reach the colon within the first 8 hours were regarded as having complete obstruction, and 34 of those patients (81.0%) underwent surgery; 8 (19.0%) received conservative treatment. Adhesion bands with complete bowel obstruction were observed in all 34 patients (100.0%) during laparotomy. Regardless of the presence of an air-fluid level on a plain abdominal radiograph or abdominal pain, a liquid diet followed by a soft diet could be given to those patients whose Urografin emptied into the colon. All the patients with partial bowel obstruction were treated successfully with nonoperative methods. The presence of Urografin in the colon within 8 hours of ingestion as an indicator for nonoperative treatment had a sensitivity of 90.2%, a specificity of 100%, and an accuracy of 93. 1%. Urografin, a safe and reliable water-soluble contrast medium, can be used to differentiate partial intestinal obstruction from complete intestinal obstruction. Early oral intake was found to be a major advantage of Urografin use in this study, and the potential of Urografin use to shorten the period of conservative treatment for postoperative small bowel obstruction needs further investigation.", "The aim of the present study to examine the use of a modified water-soluble follow-through in the diagnosis and management of small bowel obstruction (SBO).\n Sixty-two patients were recruited to the study: 33 into the control group and 29 into the study group. A modified small bowel follow-through (SBFT) was performed in the study group patients. The control group was managed conventionally. Assessment was made by questionnaire documenting initial surgical diagnosis and likelihood of operative intervention, final diagnosis and surgical outcome (operative versus non-operative).\n SBFT changed the diagnosis in 12/24 of the study group (p<0.01). In the study group 8/24 proceeded to surgery whereas 19/33 underwent laparotomy in the control group, representing a relative risk reduction of 52%, but this was not statistically significant (0.10>p>0.05, chi-squared test).\n SBFT remains a valid and useful tool in surgical management of SBO. In particular it aids diagnostic confidence in planning surgical intervention, particularly in uncomplicated patients.", "A series of 127 consecutive patients with symptoms and signs and radiological features suggestive of acute small bowel obstruction underwent water-soluble contrast small bowel follow-through examination. A dose of 100 ml of Gastrograffin in adults, or 20-50 ml in children, was injected via a nasogastric tube and supine plain abdominal radiographs were taken at 30 min and 4 h after administration. If contrast passed to the colon a non-operative course was followed. If there was a clear cut-off in contrast level in the small bowel or if contrast failed to pass into the large bowel by 4 h, patients underwent laparotomy. Based on these radiological findings 15 patients (11.8%) underwent surgery and all had established small bowel obstruction at laparotomy. The remaining 112 patients were successfully managed conservatively. Water-soluble contrast radiology is safe, easy to use and to interpret, and is a major benefit in differentiating mechanical from other causes of small bowel obstruction. Our experience indicates that this underused technique is of significant value in identifying those patients who require urgent surgery.", "Hyperosmotic water-soluble contrast materials have been fo und to be helpful diagnostic tools in postoperative small-bowel obstruction (POSBO); however, their therapeutic value remains controversial.\n A prospective, randomized clinical study was conducted to examine the use of meglumine ioxitalamate as a supplement to the standard conservative treatment of POSBO. Patients with POSBO (n = 50) suitable for a conservative approach were randomized to receive standard conservative treatment with (n = 25) or without (n = 25) the addition of 100 mL of meglumine ioxitalamate via the nasogastric tube (patients with diffuse carcinomatosis and early POSBO were excluded). Both groups were compared for resolution of obstruction, need for surgical relief of obstruction, and complications.\n Seven (14%) patients required surgery: 3 in the contrast material group and 4 in the control group (P = not significant [NA]. Resolution of symptoms was achieved in nonsurgical patients within an average of 25.7 hours in the contrast material group and 28.7 hours in the control group (P = NS). There was no mortality in this study. In 2 (4%) patients (1 in each group), strangulated bowel was found during surgery, but only the 1 (2%) patient in the contrast material group required bowel resection. No difference was found in the length of hospital stay or rate of complications. There were no complications that could be attributed to the use of the contrast material itself.\n Although water-soluble contrast material is a safe and useful diagnostic tool, it offers no advantage as a supplement to the usual conservative treatment of POSBO." ]

[ "10452769", "9655716" ]

[ "Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.", "A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy." ]

[ "Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects.\n We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens.\n Twenty asthmatic children sensitized to pet allergens (cat/dog) and with an animal at home participated in a double-blind, placebo-controlled, cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners. Before and after each study period, lung function, airway hyperresponsiveness (adenosine monophosphate), and peak flow variation were recorded. Cat and dog allergen levels were assessed in the filters of the air cleaners.\n After a 3-month intervention with active air cleaners, airway hyperresponsiveness decreased significantly, showing a 1.2 doubling dose increase of PC(20 )adenosine (P =.003). Peak flow amplitude also decreased (P =. 045). Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well. Allergen levels in floor dust were not changed.\n In young asthmatic patients sensitized and exposed to pets in the home, application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude.", "To evaluate the effect of a room high-efficiency particulate air (HEPA) cleaner on cat-induced asthma and rhinitis, 35 cat-allergic subjects who were living with one or more cats were studied in a double-blind, placebo controlled trial. After a 1 mo baseline period, subjects' bedrooms were equipped with an active or placebo air cleaner for the following 3 mo. Evaluations included monthly measurement of cat-allergen levels, daily morning, afternoon, and nighttime nasal- and chest-symptom scores, twice-daily measurement of peak-flow rates, daily medication scores, monthly spirometry, and methacholine (MCh) challenge testing before and after the study. Airborne allergen levels were reduced in the active-filter group as compared with the placebo group (p = 0.045). However, no differences were detected in settled-dust allergen levels (p = 0.485), morning, afternoon, or nighttime nasal-symptom scores (p = 0.769, 0.534, and 0.138), chest-symptom scores (p = 0.388, 0.179, and 0.215), sleep disturbance (p = 0.101), morning or afternoon peak-flow rates (p = 0. 424 and 0.679), or rescue medication use (nasal, p = 0.164, chest, p = 0.650), respectively. Although the combination of a HEPA room air cleaner, mattress and pillow covers, and cat exclusion from the bedroom did reduce airborne cat-allergen levels, no effect on disease activity was detected for any parameter studied." ]

[ "8520759" ]

[ "Low-dose nebulized morphine does not improve exercise in interstitial lung disease." ]

[ "Recent reports have suggested that low-dose nebulized morphine may improve exercise tolerance in patients with interstitial lung disease (ILD) by acting on peripheral opioid-sensitive pulmonary receptors. We therefore examined whether the administration of low-dose nebulized morphine would influence dyspnea or the breathing pattern during exercise of subjects with ILD and improve their exercise performance. Each of six subjects with ILD underwent three maximal incremental cycle ergometer tests, each test separated from the last by at least 3 d. Each exercise test was similar except that 30 min before exercise, the subjects received nebulized saline (control), morphine 2.5 mg, or morphine 5.0 mg, respectively, in double-blinded fashion. No significant differences were noted in exercise duration, maximal workload, or sense of dyspnea at the end of exercise in the control test and the tests with either morphine 2.5 mg or morphine 5.0 mg. Nor were significant differences noted in resting, submaximal, or end-exercise measurements of oxygen uptake (VO2), carbon dioxide output (VCO2), end-tidal CO2 (PETCO2), oxygen saturation (SaO2), minute ventilation (VI), respiratory frequency (f), tidal volume (VT), or heart rate (HR) in the three tests. Low-dose nebulized morphine did not alter the subjects' breathing pattern or affect the relationship between dyspnea and ventilation during exercise. No significant side effects were noted. The administration of low-dose nebulized morphine to subjects with ILD neither relieves their dyspnea during exercise nor improves their maximal exercise performance." ]

[ "17434505", "11098042", "16603437" ]

[ "A multicenter randomized, controlled study comparing laparoscopic versus minilaparotomic myomectomy: reproductive outcomes.", "Fertility and obstetric outcome after laparoscopic myomectomy of large myomata: a randomized comparison with abdominal myomectomy.", "Effects of the position of fibroids on fertility." ]

[ "To assess the reproductive outcomes after minilaparotomic and laparoscopic myomectomy in patients wishing to conceive.\n Randomized controlled trial.\n Departments of obstetrics and gynecology of the universities of Catanzaro, Rome, and Florence, Italy.\n One hundred thirty-six women with symptomatic uterine leiomyomas or unexplained infertility.\n Laparoscopic and minilaparotomic myomectomy.\n Pregnancy, abortion, and live-birth rates.\n Between the laparoscopic and minilaparotomic groups no difference was observed in cumulative pregnancy, live-birth, and abortion rates, whereas pregnancy and live-birth rates per cycle, and time to first pregnancy and live-birth were significantly higher in the laparoscopic than in the minilaparotomic group. Categorizing the patients according to surgical indication for myomectomy, cumulative pregnancy rate, pregnancy, and live-birth rates per cycle, and time to first pregnancy and live-birth were significantly better after laparoscopic myomectomy in symptomatic patients, whereas all reproductive outcomes were similar between the two groups in patients with unexplained infertility.\n Minilaparotomic and laparoscopic myomectomy improves in a similar manner the reproductive outcomes in patients with unexplained infertility, whereas the laparoscopic approach provides the best benefits in fertile patients with symptomatic leiomyomas.", "The purpose of this study was to compare, in infertile patients, the efficacy of laparoscopic myomectomy versus abdominal myomectomy, in restoring fertility and to evaluate the obstetric outcomes. Between January 1993 and January 1998, 131 patients of reproductive age, with anamnesis of infertility, underwent myomectomy because of the presence of at least one large myoma (diameter greater than or = 5 cm). Patients were randomly selected for treatment by laparotomy (n = 65) or laparoscopy (n = 66). The two groups were homogeneous for number, size and position of large myomata. Significant differences were found in the post-operative outcome: febrile morbidity (> 38 degrees C) was more frequent in the abdominal than in the laparoscopic group (26.2 versus 12.1%; P < 0.05). Laparotomy caused a more pronounced haemoglobin drop (2.17 +/- 1.57 versus 1.33 +/- 1.23; P < 0.001); three patients received a blood transfusion after laparotomy and none after laparoscopy. The post-operative hospital stay was shorter in the laparoscopic group (142.80 +/- 34.60 versus 75.61 +/- 37.09 h; P < 0.001). No significant differences were found between the two groups as concerns pregnancy rate (55.9% after laparotomy, 53.6% after laparoscopy), abortion rate (12.1 versus 20%), preterm delivery (7.4 versus 5%) and the use of Caesarean section (77.8 versus 65%). No case of uterine rupture during pregnancy or labour was observed.", "This prospective, controlled study was performed in order to evaluate whether the location of uterine fibroids may influence reproductive function in women and whether removal of the fibroid prior to conception may improve pregnancy rate and pregnancy maintenance. We examined 181 women affected by uterine fibroids who had been trying to conceive for at least 1 year without success. The main outcome measures were the pregnancy rate and the miscarriage rate. Among the patients who underwent myomectomy, the pregnancy rates obtained were 43.3% in cases of submucosal, 56.5% in cases of intramural, 40.0% in cases of submucosal-intramural and 35.5% in cases of intramural-subserosal uterine fibroids, respectively. Among the patients who did not undergo surgical treatment, the pregnancy rates obtained were 27.2% in women with submucosal, 41.0% in women with intramural, 15.0% in women with submucosal-intramural and 21.43% in women with intramural-subserosal uterine fibroids, respectively. Although the results were not statistically significant in the group of women with intramural and intramural-subserosal fibroids, this study confirms the important role of the position of the uterine fibroid in infertility as well as the importance of fibroids removal before the achievement of a pregnancy, to improve both the chances of fertilization and pregnancy maintenance." ]

[ "11300432", "12799402", "2761587" ]

[ "Ticlopidine versus aspirin after myocardial infarction (STAMI) trial.", "Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial.", "A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group." ]

[ "We sought to compare the efficacy of aspirin and ticlopidine in survivors of acute myocardial infarction (AMI) treated with thrombolysis.\n The role of ticlopidine in secondary prevention after AMI has not yet been explored.\n Of 4,696 patients with AMI treated with thrombolysis who were screened, 261 died in the hospital (5.6%) and 1,470 were enrolled in this randomized, double-blind, multicenter trial and allocated to treatment with either aspirin (160 mg/day) or ticlopidine (500 mg/day). The most frequent reasons for exclusion were refusal to give informed consent, planned myocardial revascularization, risk of noncompliance with study procedures, need for anticoagulant therapy and contraindications to the study treatments. The primary end point was the first occurrence of any of the following events during the six-month follow-up: fatal and nonfatal AMI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death or death due to any other cause.\n The primary end point was recorded in 59 (8.0%) of the 736 aspirin-treated and 59 (8.0%) of the 734 ticlopidine-treated patients (p = 0.966). Vascular death was the first event in five patients taking aspirin and in six patients taking ticlopidine (0.7% vs. 0.8%; p = NS); nonfatal AMI in 18 and 8 (2.4% vs. 1.1%; p = 0.049); nonfatal stroke in 3 and 4 (0.4% vs. 0.5%; p = NS); and angina in 33 and 40 (4.5% vs. 5.4%; p = NS), respectively. The frequency of adverse reactions was not significantly different between the two groups.\n No difference was found between the ticlopidine and aspirin groups in the rate of the primary combined end point of death, recurrent AMI, stroke and angina.", "Blacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke.\n To determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients.\n Randomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years.\n A total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin.\n Recurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.\n The blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P =.12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P =.08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P =.12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P =.69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis.\n During a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke.", "We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater." ]

[ "11295003", "12785670", "11911510" ]

[ "Efficacy of an energy conservation course for persons with multiple sclerosis.", "Effects of an energy conservation course on fatigue impact for persons with progressive multiple sclerosis.", "Evaluation of the effectiveness of professionally guided self-care for people with multiple sclerosis living in the community: a randomized controlled trial." ]

[ "To evaluate the efficacy of an energy conservation course on fatigue impact, self-efficacy, and quality of life (QOL) for persons with multiple sclerosis (MS).\n Repeated measures with control and experimental interventions conducted during a 19-week study.\n Community-based treatment center.\n A convenience sample of 54 individuals from 79 community-dwelling volunteers with fatigue secondary to MS.\n A 6-session, 2-hr/wk energy conservation course taught by occupational therapists for groups of 8 to 10 participants.\n Fatigue Impact Scale (self-report measure of fatigue impact on cognitive, physical, social functions), Self-Efficacy Gauge (self-report measure of confidence in ability to perform specific behaviors), and Medical Outcomes Study Short-Form Health Survey (QOL measure).\n Participants reported, as predicted, significantly less fatigue impact, increased self-efficacy, and improved QOL (ie, 3 of 4 subscales expected to improve). There were no significant differences, as predicted, in any of the dependent variables after the control (ie, support group) and no intervention periods.\n Results provide strong evidence for the efficacy of this energy conservation course for persons with MS.", "Fatigue is a common, troublesome symptom for persons with multiple sclerosis. This study evaluated the effects of an energy conservation course on fatigue impact for persons with multiple sclerosis whose symptoms cause moderate to severe disability.\n Thirty-seven persons with progressive multiple sclerosis participated in an 8-week experimental energy conservation course treatment and an 8-week control period of traditional treatment using a crossover design. The Fatigue Impact Scale (FIS) was used to assess fatigue impact before and after the experimental and control periods, and 8 weeks post-energy conservation course.\n After participation in the energy conservation course, the average FIS total score and physical, cognitive, and psychosocial subscale scores decreased significantly, whereas the total and subscale scores did not change significantly during the control period. Additionally, decreased fatigue impact was maintained 8 weeks after course completion for evaluated participants.\n This study provides evidence that this energy conservation course can be a beneficial intervention for persons with progressive multiple sclerosis.", "The aim of the study was to assess the efficacy of a patient-focused professionally guided self-care programme for the management of multiple sclerosis (MS) in the community.\n This was a single-blind randomized controlled trial.\n The study was conducted with people with MS living in the community.\n Two hundred and seventy-eight people with MS were invited to take part in the study. One hundred and eighty-nine people consented to take part (68%). Of these 183 began the study and 169 (92.3%) completed it. Seventy-three individuals were in the intervention group and 96 were in the control group.\n The intervention comprised discussion of self-care based on client priorities, using an information booklet about self-care.\n These included the Barthel Index, a measure of mobility, the SF-36, and the Standard Day Dependency Record (SDDR) which measures the need for assistance with daily activities. Assessments were conducted at baseline and again six months later.\n Changes in health status were small. However, at follow-up the intervention group had better SF-36 health scores, in mental health (p = 0.04), and vitality (p = 0.05) and considered help with daily activities to be less essential, as measured by the SDDR (p = 0.04), than the control group. Participants in the intervention group had maintained levels of independence at follow-up (p = 0.62) while the control group showed a significant decrease in independence (p= 0.001).\n This intervention could be a useful aid for health professionals who are supporting people with MS living in the community." ]

[ "21508941", "19433702", "16534045", "20059474" ]

[ "Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria.", "A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial.", "Role of pharmacist counseling in preventing adverse drug events after hospitalization.", "The effect of systematic medication review in elderly patients admitted to an acute ward of internal medicine." ]

[ "Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events (ADEs), hospitalization, and wasteful utilization of resources. We randomized 400 hospitalized patients aged ≥ 65 years to receive either the usual pharmaceutical care (control) or screening with STOPP/START criteria followed up with recommendations to their attending physicians (intervention). The Medication Appropriateness Index (MAI) and Assessment of Underutilization (AOU) index were used to assess prescribing appropriateness, both at the time of discharge and for 6 months after discharge. Unnecessary polypharmacy, the use of drugs at incorrect doses, and potential drug-drug and drug-disease interactions were significantly lower in the intervention group at discharge (absolute risk reduction 35.7%, number needed to screen to yield improvement in MAI = 2.8 (95% confidence interval 2.2-3.8)). Underutilization of clinically indicated medications was also reduced (absolute risk reduction 21.2%, number needed to screen to yield reduction in AOU = 4.7 (95% confidence interval 3.4-7.5)). Significant improvements in prescribing appropriateness were sustained for 6 months after discharge.", "Patients 80 years or older are underrepresented in scientific studies. The objective of this study was to investigate the effectiveness of interventions performed by ward-based pharmacists in reducing morbidity and use of hospital care among older patients.\n A randomized controlled study of patients 80 years or older was conducted at the University Hospital of Uppsala, Uppsala, Sweden. Four hundred patients were recruited consecutively between October 1, 2005, and June 30, 2006, and were randomized to control (n = 201) and intervention (n = 199) groups. The interventions were performed by ward-based pharmacists. The control group received standard care without direct involvement of pharmacists at the ward level. The primary outcome measure was the frequency of hospital visits (emergency department and readmissions [total and drug-related]) during the 12-month follow-up period.\n Three hundred sixty-eight patients (182 in the intervention group and 186 in the control group) were analyzed. For the intervention group, there was a 16% reduction in all visits to the hospital (quotient, 1.88 vs 2.24; estimate, 0.84; 95% confidence interval [CI], 0.72-0.99) and a 47% reduction in visits to the emergency department (quotient, 0.35 vs 0.66; estimate, 0.53; 95% CI, 0.37-0.75). Drug-related readmissions were reduced by 80% (quotient, 0.06 vs 0.32; estimate, 0.20; 95% CI, 0.10-0.41). After inclusion of the intervention costs, the total cost per patient in the intervention group was $230 lower than that in the control group.\n If implemented on a population basis, the addition of pharmacists to health care teams would lead to major reductions in morbidity and health care costs.", "Hospitalization and subsequent discharge home often involve discontinuity of care, multiple changes in medication regimens, and inadequate patient education, which can lead to adverse drug events (ADEs) and avoidable health care utilization. Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs.\n We conducted a randomized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital. Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later. Interventions focused on clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate. The primary outcome was rate of preventable ADEs.\n Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients' preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization.\n Pharmacist medication review, patient counseling, and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge. Medication discrepancies before and after discharge were common targets of intervention.", "Elderly patients are vulnerable to medication errors and adverse drug events due to increased morbidity, polypharmacy and inappropriate interactions. The objective of this study was to investigate whether systematic medication review and counselling performed by a clinical pharmacist and clinical pharmacologist would reduce length of in-hospital stay in elderly patients admitted to an acute ward of internal medicine. A randomized, controlled study of 100 patients aged 70 years or older was conducted in an acute ward of internal medicine in Denmark. Intervention arm: a clinical pharmacist conducted systematic medication reviews after an experienced medical physician had prescribed the patients' medication. Information was collected from medical charts, interview with the patients and database registrations of drug purchase. Subsequently, medication histories were conferred with a clinical pharmacologist and advisory notes recommending medication changes were completed. Physicians were not obliged to comply with the recommendations. Control arm: medication was reviewed by usual routine in the ward. Primary end-point was length of in-hospital stay. In addition, readmissions, mortality, contact to primary healthcare and quality of life were measured at 3-month follow-up. In the intervention arm, the mean length of in-hospital stay was 239.9 hr (95% CI: 190.2-289.6) and in the control arm: 238.6 hr (95% CI: 137.6-339.6), which was neither a statistical significant nor a clinically relevant difference. Moreover, no differences were observed for any of the secondary end-points. Systematic medication review and medication counselling did not show any effect on in-hospital length of stay in elderly patients when admitted to an acute ward of internal medicine." ]

[ "10505365", "7484865", "10628024", "7621734", "1505329", "1606113", "8722429" ]

[ "Telemedicine in the emergency department: a randomized controlled trial.", "Cardiac rehabilitation using simultaneous voice and electrocardiographic transtelephonic monitoring.", "Virtual outreach: a telemedicine pilot study using a cluster-randomized controlled design.", "Using telecommunication technology to manage children with diabetes: the Computer-Linked Outpatient Clinic (CLOC) Study.", "Telephone modem access improves diabetes control in those with insulin-requiring diabetes.", "Objective measurement of anxiety in hypertensive pregnant women managed in hospital and in the community.", "A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control." ]

[ "Emergency physicians and nurses were trained in telemedicine techniques in two emergency departments, one rural (low volume) and one suburban (high volume). Fifteen patient complaints were selected as appropriate for the study. Of 122 patients who met the inclusion criteria, 104 (85%) consented to participate. They were randomized to control and experimental groups. The suburban emergency physician diagnosed and treated the control patients. Experimental patients presenting to the high-volume emergency department were evaluated and treated by the telemedicine nurse in person and the rural emergency physician via the telemedicine link. Immediately before discharge all telemedicine patients were re-evaluated by the suburban emergency physician. Data collected on each patient included: diagnosis; treatment; 72 h return visits; need for additional care; and satisfaction of patient, physicians and nurses. There were no significant differences (P > 0.05) for occurrence of 72 h return visits, need for additional care or overall patient satisfaction. The average patient throughput time (from admission to discharge) was 106 min for the telemedicine group and 117 min for the control group. Telemedicine was a satisfactory technique for the chosen group of patients in the emergency department and was acceptable to the participants.", "nan", "A pilot study was carried out in preparation for a full-scale randomized controlled trial of teleconsultations versus routine outpatient consultation. The method of study recruited sufficient numbers of patients and avoided selection bias. Over five months, 439 referrals were received, but 297 patients were not eligible to enter the trial because they did not fall within the specialties/consultants included in it. Of the 132 referrals entering the trial, 62 were randomized to the intervention group and 70 to the control group. Consent to participate in the experimental arm of the trial was obtained for all but 13 patients. The results also suggested that patient satisfaction with teleconsultation may exceed that with conventional outpatient consultation, with a strong indication of overall time savings for patients.", "The purpose of this study was to evaluate the efficacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin-dependent diabetes. Metabolic control, patients' psychosocial status, family functioning, perceived quality of life, patterns of parental/child responsibility for daily diabetes maintenance, and nursing time-on-task were evaluated. One hundred six pediatric patients (mean age = 13.3 years) were randomly assigned to an experimental or control outpatient clinic for 1 year. Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks. Transmitted data were reviewed by nurse practitioners who telephoned subjects to discuss regimen adjustments. Control subjects received standard care with regimen adjustments made by physicians. There were no significant between-group differences for metabolic control, rates of hospitalization or emergency-room visits, psychological status, general family functioning, quality of life, or parent-child responsibility. A significant decrease was noted in nursing time-on-task for experimental subjects.", "To assess whether modem access improves diabetes control in IDDM patients.\n Forty-two patients participated in the study and were followed for 12 wk. The patients were randomly divided into two groups at baseline, a modem group and a control group. There were no significant differences between HbA1c, random blood glucose, and weight between the groups at the beginning of the study. Patients were asked to perform five blood glucose determinations/day (before breakfast, before lunch, afternoon [1500], before dinner, and at bedtime) twice/week. The modem group transferred their data over the phone once/week. The control group would bring in their results on their regular visits every 6 wk. Patients in the modem group were counseled every week over the telephone after transferring results to adjust insulin and food intake if necessary.\n In the modem group, HbA1c improved from 0.106 to 0.092 (13.20%). The control group improved from 0.112 to 0.102 (8.9%). There was no significant change in weight, random blood glucose, or insulin.\n The use of telephone modem-based patient-monitoring systems in diabetes clinical research seems to stimulate the patient to keep closer control of blood glucose levels. It might be especially useful in rural settings, for which this study was designed.", "To determine whether pregnant hypertensives women are more anxious when monitored in hospital or at homes.\n Prospective randomized controlled trial.\n Rosie Maternity Hospital and women's homes.\n Ninety-nine pregnant hypertensive women: 50 had their blood pressure measured telemetrically from home, and 49 had it measured in hospital.\n Number of episodes of monitoring, duration of monitoring, mean blood pressure during monitoring, gestational age at delivery, trait and state anxiety levels.\n There were no significant differences in anxiety levels, or in any other outcome measure, between the home and hospital groups.\n When blood pressure is being monitored serially in pregnant hypertensive women, there is no measurable difference in their anxiety levels, whether they are in hospital or at home.", "This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control. A randomized controlled trial was conducted in 29 greater Boston communities. The study subjects were 267 patients recruited from community sites who were >or= 60 years of age, on antihypertensive medication, with a systolic blood pressure (SBP) of >or= 160 mm Hg and/or a diastolic blood pressure (DBP) of >or= 90 mm Hg. The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months. Weekly, subjects in the telephone group reported self-measured blood pressures, knowledge and adherence to antihypertensive medication regimens, and medication side-effects. This information was sent to their physicians regularly. The main study outcome measures were change in antihypertensive medication adherence, SBP and DBP during 6 months, satisfaction of patient users, perceived utility for physicians, and cost-effectiveness. The mean age of the study population was 76.0 years; 77% were women; 11% were black. Mean antihypertensive medication adherence improved 17.7% for telephone system users and 11.7% for controls (P = .03). Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls (P = .02). Among nonadherent subjects, mean DBP decreased 6.0 mm Hg for telephone users, but increased 2.8 mm Hg for controls (P = .01). For telephone system users, mean DBP decreased more if their medication adherence improved (P = .03). The majority of telephone system users were satisfied with the system. Most physicians integrated it into their practices. The system was cost-effective, especially for nonadherent patient users. Therefore, weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients. This system can be used to monitor patients with hypertension or with other chronic diseases, and is likely to improve health outcomes and reduce health services utilization and costs." ]

[ "7844217", "11232021", "8671231", "15374698", "10632418", "15589860", "12512925", "15567879", "9688386", "12909504", "8458457", "8281707", "15588465", "10831546", "12151445", "14680546", "10632419", "15343256", "8641492", "15219887", "16361296", "10099977", "1906152", "7962373", "14688156" ]

[ "Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles.", "Luteinzing hormone activity in menotropins optimizes folliculogenesis and treatment in controlled ovarian stimulation.", "Simplified ultralong protocol of gonadotrophin-releasing hormone agonist for ovulation induction with intrauterine insemination in patients with endometriosis.", "Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: a prospective, randomized analysis of cost effectiveness.", "Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study.", "A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation.", "Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility.", "Timing ovulation for intrauterine insemination with a GnRH antagonist.", "A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility.", "Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone.", "A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate.", "Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments.", "Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness.", "Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa.", "Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH.", "Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study.", "A randomized prospective study comparing pregnancy rates after clomiphene citrate and human menopausal gonadotropin before intrauterine insemination.", "A randomized, multicenter study comparing the efficacy of recombinant FSH vs recombinant FSH with Ganirelix during superovulation/IUI therapy.", "Menotropins alone are superior to a clomiphene citrate and menotropin combination for superovulation induction among clomiphene citrate failures.", "High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial.", "Treatment with the GnRH antagonist ganirelix prevents premature LH rises and luteinization in stimulated intrauterine insemination: results of a double-blind, placebo-controlled, multicentre trial.", "The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility.", "Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women.", "A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility.", "GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages." ]

[ "At present, there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination (IUI). Also, ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles. However, the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation, and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements. In the present prospective randomized trial, the efficacy and safety of ovarian stimulation with clomiphene citrate (50 mg/day for 5 days) and IUI (clomiphene/IUI group) were compared with those of late low-dose pure follicle stimulating hormone (FSH, 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter) and IUI (FSH/IUI group) in ovulatory women who were infertile because of unexplained infertility (n = 40) or male subfertility (n = 60). The mean length of treatment in the FSH group was 6.4 +/- 2.5 days. Multiple follicular development was seen in 25% of clomiphene-stimulated cycles but only in 8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively (P = 0.02). All pregnancies obtained were singleton. There were two and one clinical abortions in the clomiphene/IUI (50%) and FSH/IUI (8%) groups respectively. No patient developed ovarian hyperstimulation syndrome. Use of our therapeutic scheme, which proved to be efficacious, safe and economic for ovarian stimulation in IUI cycles, is advocated before the institution of in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) therapy in infertile patients with patient Fallopian tubes. This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results.", "Although the role that LH plays in folliculogenesis is still controversial, recent evidence points toward facilitatory actions of LH activity in ovulation induction. Thus, we compared the response to either highly purified FSH (75 IU FSH/ampoule; group A, 25 subjects) or human menopausal gonadotropin (75 IU FSH and 75 IU LH/ampoule; group B, 25 subjects) in normoovulatory GnRH agonist-suppressed women, candidates for intrauterine insemination. A fixed regimen of 2 daily ampoules of highly purified FSH or human menopausal gonadotropin was administered in the initial 14 days of treatment; menotropin dose adjustments were allowed thereafter. Treatment was monitored with daily blood samples for the measurement of LH, FSH, 17beta-estradiol (E(2)), progesterone, testosterone, hCG, inhibin A, and inhibin B, and transvaginal pelvic ultrasound was performed at 2-day intervals. Although preovulatory E(2) levels were similar, both the duration of treatment (16.1 +/- 0.8 vs. 12.6 +/- 0.5 days; P< 0.005) and the per cycle menotropin dose (33.6 +/- 2.4 vs. 23.6 +/- 1.1 ampoules; P < 0.005) were lower in group B. In the initial 14 treatment days the area under the curve of FSH, progesterone, testosterone, inhibin A, and inhibin B did not differ between the 2 groups, whereas LH, hCG, and E(2) areas under the curve were higher in group B. The occurrence of small follicles (<10 mm) and the inhibin B/A ratio in the late follicular phase were significantly reduced in group B. A nonsignificant trend toward a higher multiple gestation rate was present in group A (60% vs. 17%). We conclude that ovulation induction with LH activity-containing menotropins is associated with 1) shorter treatment duration, 2) lower menotropin consumption, and 3) reduced development of small ovarian follicles. These features can be exploited to develop regimens that optimize treatment outcome, lower costs, and reduce occurrence of complications such as multiple gestation and ovarian hyperstimulation.", "The present study was designed to assess the usefulness of the simplified ultralong protocol of gonadotrophin-releasing hormone agonist (GnRHa) for ovulation induction with intrauterine insemination (IUI) in patients with various stages of endometriosis. A prospective randomized trial was set up to compare the simplified ultralong protocol (ULP) and the long protocol (LP) of GnRHa for ovulation induction with IUI in patients with endometriosis. There was no evidence of other factors in infertility in any patient. In the ULP group (39 patients), 4 weeks after a single injection of 3.75 mg Decapeptyl had been given, daily s.c. administration of 0.1 mg Decapeptyl was initiated and continued for at least 2 weeks prior to ovarian stimulation. In the LP group (41 patients), daily s.c. administration of 0.1 mg Decapeptyl was initiated from the mid-luteal phase of the cycle preceding the stimulation cycle. After 14 days of administration, ovarian stimulation was started if pituitary desensitization had been achieved. The amount of gonadotrophins required, number of days of gonadotrophin administration, serum oestradiol response, and the number of mature follicles were comparable in both groups. The clinical pregnancy rate per cycle was significantly higher in the ULP group at 48.7% (19/39) compared with 26.8% (11/41) in the LP group. The miscarriage rates were 21.1% (4/19) in the ULP group and 18.2% (2/11) in the LP group. In patients with stage I or II endometriosis, there was no significant difference between the two groups with respect to clinical pregnancy rate per cycle (47.4 versus 35.0%). In patients with stage III or IV endometriosis, the clinical pregnancy rate per cycle was significantly higher in the ULP group at 50.0% (10/20) compared with 19.0% (4/21) in the LP group. This study suggests that a simplified ULP of GnRHa could give better chances of achieving pregnancy in endometriosis patients undergoing assisted reproductive technologies and that this protocol may be more useful in patients with an advanced stage of endometriosis.", "To compare the clinical results and the cost effectiveness of urinary FSH and recombinant FSH in ovarian stimulation for IUI cycles.\n Prospective, randomized trial.\n University Hospital, Perugia, and A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy.\n IUI cycles were performed in 67 infertile patients.\n Protocols of ovarian stimulation with urinary FSH or recombinant FSH were randomly assigned, for a total of 138 cycles performed (67 and 71, respectively).\n Number of mature follicles, days of stimulation, number of ampules, and IU used per cycle, biochemical/clinical pregnancy rates and cost-effectiveness ratio.\n Follicular development, length of stimulation, pregnancy and delivery rates were not statistically different. Although in the urinary FSH group a significantly higher number of IU of gonadotropins were used (815.5 +/- 284.9 vs. 596.0 +/- 253.8), the cost per cycle remained significantly lower (220.73 +/- 94.72 vs. 318.50 +/- 125.21). The cost-effectiveness ratio was 1,848.61 euro in the urinary FSH group and 2,512.61 euro in the recombinant FSH group.\n Urinary FSH and recombinant FSH are both effective in ovarian stimulation in IUI cycles. The urinary preparation is more cost effective due to the difference of its cost per IU.", "To compare the effectiveness of clomiphene citrate used alone and in combination with ethinyl E2 for the induction of ovulation in patients undergoing IUI.\n Randomized, double-blind study.\n Four infertility treatment centers.\n Women aged 25-35 years with infertility of at least 2 years' duration and oligomenorrhea or amenorrhea associated with a positive menstrual response to an IM progesterone challenge.\n A total of 64 patients were randomized to treatment with CC (100 mg daily for 5 days) or CC (100 mg daily for 5 days) plus ethinyl E2 (0.05 mg daily for 5 days).\n The uterine artery pulsatility index, number of preovulatory follicles, endometrial thickness, and pregnancy rate.\n Both treatment regimens increased FSH, LH, and 17beta-E2 levels, with no statistically significant differences. There was a statistically significant difference in endometrial thickness between the two treatment groups. No statistically significant differences were noted in pulsatility index values or in the number of preovulatory follicles.\n Ethinyl E2 can reverse the deleterious effects of CC on endometrial thickness, which may contribute to higher pregnancy rates.", "To compare the effects of the aromatase inhibitor letrozole (7.5 mg) and clomiphene citrate (CC; 100 mg) in women undergoing superovulation and IUI.\n Prospective randomized trial.\n University teaching hospital.\n We studied a total of 238 cycles of superovulation and IUI in women with idiopathic infertility.\n Patients were randomized into treatment with 7.5 mg of letrozole daily (74 patients, 115 cycles) or 100 mg of CC daily (80 patients, 123 cycles).\n Number of follicles, endometrial thickness, pregnancy rate, and miscarriage rate.\n The mean age, parity, and duration of infertility in both groups of patients were similar. There was no significant difference between the total number of developing follicles in the letrozole (5.7 +/- 3.7) and in the CC groups (4.8 +/- 2.5). The number of follicles of > or =14 mm and of >18 mm were 2.1 +/- 1.2 and 1.4 +/- 0.7 in the letrozole group, and 1.7 +/- 0.9 and 1.1 +/- 0.5 in the CC group, respectively. No difference was found in the endometrial thickness between the two groups (7.1 +/- 0.2 mm in the letrozole group, 8.2 +/- 5.9 mm in the CC group). The pregnancy rate per cycle was 11.5% in the letrozole group and 8.9% in the CC group. Four of the 11 pregnancies in the CC group resulted in a miscarriage (36.6%).\n Superovulation and IUI with letrozole and CC are associated with similar pregnancy rates, but the miscarriage rate is higher with CC. The ideal dose of letrozole remains unknown and further study is needed.", "To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI).\n A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols.\n There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols.\n Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician.", "We aimed to assess the efficacy of a GnRH antagonist in intrauterine insemination (IUI) cycles to increase number of mature ovulatory follicles and pregnancy rates.\n Prospective randomized study. Women (18-38 years old) with primary/secondary infertility were included. Eighty-two patients were randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH + GnRH antagonist or rFSH alone.\n A non-significant increase in the total amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm) was significantly higher in the GnRH antagonist group than in the control group (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly increased in the group of patients receiving the GnRH antagonist (38%) compared to the control group (14%). The only non-single pregnancy (triplets) occurred in the antagonist group.\n In this preliminary study, adding the GnRH antagonist to the COS protocol for IUI cycles significantly increased pregnancy rates. Nevertheless, these results may not be associated directly with the antagonist itself but with the fact that more mature ovulatory follicles are present by the day of the hCG. Finally, the risk for multiple gestations needs to be carefully evaluated.", "This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility.", "To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG.\n Controlled, prospective, randomized comparison of fixed gonadotropin regimens.\n Academic research institution.\n Fifty infertile patients who were candidates for IUI.\n Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen).\n Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications. Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ.\n The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.", "To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG).\n A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed.\n The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden.\n Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison.\n Pregnancy rate (PR).\n Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy.\n Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility.", "The aim of this study was to compare endocrine changes and the follicular development in patients receiving pure FSH alone or in association with LH after desensitization with an LH-RH agonist depot. Thirty four cycles were selected for this prospective randomized study. Desensitization was obtained using Goserelin the cycle before the stimulation. Induction of ovulation for IUI was carried out with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and ampules required for follicular maturation were equivalent in the two groups. The same number of follicles were developed, while different, but not significant, pregnancy rates were obtained. Estradiol values at the end of stimulation were significantly lower for FSH group. In conclusion the contemporary administration of LH with FSH does not exert any effect on follicular development, but it seems to facilitate E2 synthesis, probably providing more substrate for the aromatization process.", "The aim of this prospective, randomized trial was to compare the clinical results and the cost-effectiveness of urinary FSH (uFSH) and recombinant FSH (rFSH) in ovarian stimulation for intrauterine insemination (IUI) cycles in polycystic ovary syndrome (PCOS) patients. One-hundred and seventy PCOS infertile patients undergoing IUI were enrolled, and protocols of ovarian stimulation with uFSH or rFSH were randomly assigned. The total number of cycles performed was 379 (182 and 197, respectively). The main outcome measures were the number of mature follicles, the days of stimulation, the number of ampoules and IU used per cycle, the biochemical/clinical pregnancy rates, the number of multiple pregnancies and the cost-effectiveness. No statistically significant differences were found in the follicular development, length of stimulation, pregnancy rates, delivery rates and multiple pregnancies between the two groups. In the uFSH group, the cost per cycle remained significantly lower (218.51 +/- 88.69 versus 312.22 +/- 118.12; P < 0.0001), even though a significantly higher number of IU of gonadotrophins were used (809.3 +/- 271.9 versus 589.1 +/- 244.7; P < 0.0001). The cost-effectiveness (i. e. within a group, the total cost of all cycles divided by no. of clinical pregnancies) was 1729.08 in the uFSH group and 3075.37 in the rFSH group. In conclusion, uFSH and rFSH demonstrated the same effectiveness in ovarian stimulation in IUI cycles in PCOS patients. The urinary preparation is more cost-effective due to the difference of its cost per IU.", "A randomized trial was carried out comparing recombinant FSH (rFSH) and highly purified urinary FSH (uFSH) in intrauterine insemination (IUI) with husbands' spermatozoa. A total of 45 women received rFSH (139 cycles), while 46 women received uFSH (155 cycles). The starting dose was 150 IU/day s.c., beginning on the second day, and on days 6-7 the dose was adjusted according to ovarian response, assessed by vaginal ultrasound and plasma oestradiol concentration. The pregnancy rate according to the intention to treat was 57.8% in rFSH versus 52.2% in uFSH, the corrected pregnancy rates 56.8% and 52.2%, and the cumulative pregnancy rates 69.6% and 61.0%, but the differences were not statistically significant. The per cycle pregnancy rate was 18.12% in rFSH and 15.48% in u-FSH, also not statistically significant. In the rFSH group, the consumption of FSH ampoules per cycle was significantly lower (19.20 +/- 7.02 versus 23. 80 +/- 10.78; P < 0.0001). The ratio of oestradiol/FSH ampoules was significantly higher in rFSH (56.45 +/- 31.26 versus 46.41 +/- 29. 25; P < 0.001). These data indicate that, in IUI cycles, rFSH has a higher potency than uFSH.", "The study was conducted to compare the results of intrauterine donor insemination (DI) under ovarian stimulation with either clomiphene citrate (CC), in a fixed protocol, or FSH, with ovarian monitoring.\n Forty-nine patients were randomized using a computer-generated list to receive highly purified urinary FSH (starting dose of 150 IU) and were subjected to periodic vaginal ultrasound and estradiol determinations. HCG was given when > or =2 follicles (> or =17 mm) were identified and estradiol reached >400 pg/ml. Intrauterine insemination (IUI) was performed 36 h later. The other 51 received CC on a fixed protocol (100 mg/day from the day 5-10 of the ovarian cycle) with HCG being administered on the day 12, and IUI performed 36 h later. Up to six IUI cycles were performed on all patients if pregnancy was not reached before. Women failing to conceive in the CC group underwent IUI with FSH. The main outcome measures were intrauterine gestational sac observed by transvaginal ultrasound, per cycle and per woman pregnancy rate (PR) and multiple PR.\n The per cycle PR was significantly higher in the FSH group, 14.4% (30/209) versus 6.1% (16/261), as well as the per woman PR, 61.2% (30/49) versus 31.4% (16/51). 12.5% (2/16) of pregnancies obtained in the CC group were multiple, compared with 20% (6/30) in the FSH group. There were no triplets or higher order pregnancies in CC versus two in FSH (6.7% of pregnancies). Patients failing to conceive with CC, who later underwent intrauterine DI with FSH, had similar results to the primary FSH group: 54.3% PR per patient (19/35) and 16.0% per cycle (19/118), with a multiple PR of 31.6% (6/19). The PR for women starting with CC cycles and, if pregnancy was not obtained, continuing with six FSH cycles, was 69.2%.\n The PR obtained with CC stimulation was approximately half that obtained with FSH. There was a trend to lower multiple PR with CC. It is recommended that each case should be considered on an individual basis and the treatment options discussed with patients. In our opinion, CC could be a reasonable approach for young women with good prognosis, whereas in the remaining cases FSH would be the preferable method.", "The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle.", "To determine whether hMG offers an advantage over clomiphene citrate (CC) in achieving pregnancy after IUI with husband's sperm.\n Randomized prospective trial.\n Infertility patients in a university teaching hospital.\n Fifty-eight women under 39 years old undergoing ovulation induction before IUI.\n The women were assigned randomly to one of two treatment groups. Patients in group I (CCHH) received CC for the first two cycles and hMG for the last two cycles. Patients in group II (HHCC) received hMG for the first two cycles and CC for the last two cycles.\n Cycle fecundity rates for the two treatment modalities were compared statistically with use of life-table analysis.\n Of the 174 cycles studied, overall cycle fecundity rate was 11.11 (9 of 81 cycles) in the CCHH group and 10.75 (10 of 93 cycles) in the HHCC group. The difference was not statistically significant. The cycle fecundity rate was 14.44% (13 of 90 cycles) for cycles with CC and 7.14% (6 of 84) with hMG. The difference was not statistically significant.\n These data suggest that CC is an effective alternative to hMG in the population examined.", "The purpose of this study was to determine if use of a Gonadotropin releasing hormone (GnRH) antagonist, Ganirelix (Antagon), can improve pregnancy rates during superovulation with recombinant follicle-stimulating hormone (rFSH) followed by intrauterine insemination (IUI).\n This was a multicenter, prospective, randomized, open-label, assessor-blind, controlled trial of females (n = 54), ages 18 to 39 undergoing superovulation/IUI with up to 4 cycles of superovulation/IUI without Ganirelix (n = 66), or up to 4 cycles of superovulation/IUI with the addition of Ganirelix (n = 52).\n No statistically significant difference in clinical pregnancy rates per cycle initiated was found for patients in the treatment or control group (12% vs 7%, P =.29). Other variables assessed, including endometrial thickness, size of follicles, peak serum estradiol levels, mid-lutea progesterone levels, and total vials of rFSH used also showed no statistically significant difference.\n Superovulation/IUI cycles using Ganirelix produce similar pregnancy rates when compared with cycles not using a GnRH antagonist, although there is a trend towards better pregnancy rates in cycles with Ganirelix.", "To examine the difference in efficacy between two protocols of superovulation induction with IUI among infertile couples.\n A prospective randomized trial.\n Normal human volunteers in an infertility clinic.\n Consecutively treated patients attending our infertility clinic for superovulation induction with IUI who had been unsuccessfully treated by clomiphene citrate (CC).\n Infertile couples were randomized to undergo one of two controlled ovarian hyperstimulation protocols. Group A patients received daily hMG beginning on cycle day 3, whereas group B patients were administered CC days 3 through 7, followed by hMG from day 7 onward. Randomization was performed using a random numbers table. In both groups, ovulation was triggered by 5,000 IU hCG and IUI was performed by 36 hours.\n Studied cycle performance parameters included peak E2, number of dominant and intermediate-sized follicles recruited, endometrial thickness and pattern, and frequency of monitoring.\n Data analysis demonstrated no significant difference between the two groups with respect to patient age, parity, weight, indication for superovulation and IUI, number of dominant follicles recruited, peak E2, or mean number of total motile sperm inseminated. Endometrial thickness and pattern differed between treatments, however, with group A demonstrating relatively thicker and proportionately more trilaminar patterns than group B. Group A had significantly more serum E2 measurements, as well as transvaginal sonograms performed, when compared with group B. Pregnancy rates for groups A and B were 0.192 and 0.091, respectively. Of 25 pregnancies in group A, 7 (0.28) were multiples, whereas there were no multiple gestations in group B.\n For patients undergoing superovulation with IUI, a menotropin-alone protocol yields significantly higher pregnancy rates than one using a combination of menotropin with CC. These differences could not be explained by patient characteristics. Among cycle performance parameters, endometrial thickness and pattern differed significantly between the two groups.", "To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study.\n A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate.\n Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted.\n A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.", "This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH+progesterone rises).\n Women of infertile couples, diagnosed with unexplained or male factor infertility, were randomized to receive either ganirelix (n=103) or placebo (n=100) in a double-blind design. All women were treated with an individualized, low-dose rFSH regimen started on day 2-3 of cycle. Ganirelix (0.25 mg/day) was started if one or more follicles>or=14 mm were visualized. Ovulation was triggered by HCG injection when at least one follicle>or=18 mm was observed and a single IUI was performed 34-42 h later. The primary efficacy outcome was the incidence of premature LH rises (+/-progesterone rise).\n In the ganirelix group, four subjects had a premature LH rise (value>or=10 IU/l), one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment, whereas in the placebo group 28 subjects had a premature LH rise, six subjects prior to the start of placebo and 22 subjects during placebo treatment. The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles (3.9 versus 28.0%; P=0.003 for ITT analysis). When excluding subjects with an LH value>or=10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles (2.9 versus 23.4%; P=0.003 for ITT analysis). Premature luteinization (LH rise with concomitant progesterone rise>or=1 ng/ml) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation. Ongoing pregnancy rates per attempt were 12.6 and 12.0% for the ganirelix and placebo groups respectively.\n Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working.", "The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.3%) and seven of 48 (14.6%) respectively]. A significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) was observed in the low-dose group (8.3% versus 27.1%, P < 0.05). The incidence of moderate OHSS requiring hospitalization was reduced significantly in the low-dose group (low-dose 0% versus conventional 16.7%, P < 0.01). However, the low-dose protocol did not completely prevent multiple pregnancies. Our results suggest that the low-dose step-up FSH treatment appeared to be useful for the treatment of unexplained infertility because of the high pregnancy rates and the significant decrease in the incidence of OHSS.", "Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.", "The use of gonadotrophin-releasing hormone agonist (GnRHa) in combination with human menopausal gonadotrophin (HMG) for ovulation induction has been advocated for the treatment, particularly by in-vitro fertilization (IVF) of various types of infertility. The present study was designed to compare the clinical efficacy of HMG alone with a short protocol of GnRHa/HMG for treatment of unexplained infertility. A total of 91 couples with unexplained infertility were randomly assigned to one of two treatments; either HMG with intra-uterine insemination (IUI) (45 patients, 62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments. Progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration were significantly higher in HMG (1.5 +/- 0.9 ng/ml) versus GnRHa/HMG (0.8 +/- 0.6 ng/ml; P < 0.05) cycles. Furthermore, GnRHa suppressed the occurrences of premature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively). However, there were no significant differences in HMG dose requirements, plasma oestradiol concentrations or follicular development on the day of HCG administration between the two groups. Nor were any significant differences found in the pregnancy rates between the two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively). Our results suggest no beneficial effect of GnRHa/HMG compared to HMG alone for the treatment of unexplained infertility, based on pregnancy rates.", "The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use.\n Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection.\n The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005).\n A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination." ]

[ "16966497", "10802793", "17724283", "12601104", "1647496", "8396833" ]

[ "Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study.", "Oral zolmitriptan is effective in the acute treatment of cluster headache.", "Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study.", "Intranasal sumatriptan in cluster headache: randomized placebo-controlled double-blind study.", "Treatment of acute cluster headache with sumatriptan. The Sumatriptan Cluster Headache Study Group.", "Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. The Sumatriptan Cluster Headache Study Group." ]

[ "Cluster headache is a form of primary headache in which attacks are rapid in onset with very severe pain. The mainstays of acute therapy are inhaled oxygen and sumatriptan succinate injection.\n To evaluate zolmitriptan nasal spray in the acute treatment of cluster headache.\n Ninety-two patients, aged 40 +/- 10 years (mean +/- SD) (80 men and 12 women), with International Headache Society-defined cluster headache were randomized into a placebo-controlled, double-blind crossover study. Patients treated 3 headache attacks using placebo for 1 attack, 5 mg of zolmitriptan nasal spray (ZNS5) for 1 attack, and 10 mg of zolmitriptan nasal spray for 1 attack. The primary end point was headache relief at 30 minutes, defined as reduction from moderate, severe, or very severe pain to no or mild pain. The study was approved by the appropriate ethics committees.\n Sixty-nine patients were available for an intention-to-treat analysis. The 30-minute headache relief rates were placebo, 21%; ZNS5, 40%; and ZNS10, 62%. Modeling the response as a binary outcome, the Wald test was significant for the overall regression (chi(2)(1) = 29.4; P<.001), with both ZNS5 and ZNS10 giving significant effects against placebo. Headache relief rates for patients with episodic cluster headache were 30% for placebo, 47% for ZNS5, and 80% for ZNS10, while corresponding rates for patients with chronic cluster headache were 14%, 28%, and 36%, respectively. Zolmitriptan was also well tolerated.\n Five-milligram and 10-mg doses of zolmitriptan intranasal spray are effective within 30 minutes and well tolerated in the treatment of acute cluster headache. Trial Registration controlled-trials.com Identifier ISCRTN27362692.", "To evaluate the efficacy and tolerability of oral zolmitriptan 5 mg and 10 mg and placebo in cluster headache.\n A multicenter, double-blind, randomized, three-period, crossover, outpatient study. Adult patients received placebo and zolmitriptan 5 mg and 10 mg orally for the acute treatment of episodic or chronic cluster headache. Headache intensity was rated by a five-point scale: none, mild, moderate, severe, or very severe. Patients only treated moderate to very severe headaches. The primary efficacy measure was headache response (two-point or greater reduction from baseline in the cluster headache rating scale) at 30 minutes. Secondary efficacy measures included proportion of patients with initial headache relief within 15 and 30 minutes, mild or no pain at 30 minutes, meaningful headache relief, and use of escape medication.\n A total of 124 patients took at least one dose of study medication, with 73% having episodic and 27% chronic cluster headache. For the primary endpoint, there was a treatment-by-cluster-headache-type interaction (p = 0.0453). Therefore, results are presented separately for chronic and episodic cluster headache. In patients with episodic cluster headache, the difference between zolmitriptan 10 mg and placebo at 30 minutes reached significance (47% versus 29%; p = 0.02). Mild or no pain at 30 minutes was reported by 60%, 57%, and 42% patients treated with zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo (both p </= 0.01 versus placebo). For all other secondary endpoints, zolmitriptan 10 mg was significantly superior to placebo in episodic cluster headache patients, whereas zolmitriptan 5 mg was significantly superior to placebo for three of the four secondary endpoints. In patients with chronic cluster headache, response rates following zolmitriptan 5 mg or 10 mg were not significantly different from placebo at any endpoint. Zolmitriptan 5 mg and 10 mg were well tolerated.\n Oral zolmitriptan is efficacious in episodic cluster headache.", "To evaluate the efficacy and tolerability of zolmitriptan 5 mg and 10 mg nasal spray (ZNS) vs placebo in the acute treatment of cluster headache. Design/\n We conducted a multicenter, double-blind, randomized, three-period crossover study using ZNS 5 mg, ZNS 10 mg, and placebo. Headache intensity was rated by a 5-point scale: none, mild, moderate, severe, or very severe. The primary efficacy measure was headache response (pain reduced from moderate, severe, or very severe at baseline, to mild or none) at 30 minutes. Logistic regression was used to account for treatment period effect as well as for cluster headache subtype effect.\n A total of 52 adult patients treated 151 attacks. For the primary endpoint, both doses reached significance at 30 minutes (placebo = 30%, ZNS 5 mg = 50%, ZNS 10 mg = 63.3%). For headache relief, ZNS 10 mg separated from placebo at 10 minutes (24.5% vs 10%). Zolmitriptan 5 mg separated from placebo at 20 minutes (38.5% vs 20%). For pain-free status, ZNS 10 mg was superior to placebo at 15 minutes (22.0% vs 6%). Both doses had higher pain-free rates than placebo at 30 minutes (placebo = 20%, ZNS 5 mg = 38.5%, ZNS 10 mg = 46.9%). Side effects were mild and seen in 16% of those attacks treated with placebo, 25% of attacks treated with ZNS 5 mg, and 32.7% treated with ZNS 10 mg. Conclusions/Relevance: Zolmitriptan nasal spray, at doses of 5 and 10 mg, is effective and tolerable for the acute treatment of cluster headache.", "Current evidence-based acute treatments of cluster headache are limited to oxygen inhalation and subcutaneous sumatriptan. Intranasal sumatriptan is a new formulation with better tolerability than the subcutaneous route. Two open-label studies suggested efficacy of intranasal sumatriptan in cluster headache.\n In a double-blind placebo-controlled randomized trial, patients with episodic or chronic cluster headache whose attacks lasted at least 45 minutes each treated one attack with 20 mg sumatriptan nasal spray and another one, at least 24 hours later, with matching placebo. They scored their headache on a five-point scale (very severe, severe, moderate, mild, or none) at 5, 10, 15, 20, and 30 minutes. The primary outcome measure was headache response (a decrease in pain from very severe, severe, or moderate to mild or none) at 30 minutes. Secondary outcome measures included pain-free rates, relief of associated symptoms, and rates of adverse events. Multilevel multivariate analysis was used for statistical analysis.\n Five study centers enrolled 118 patients in whom 154 attacks were treated: 77 with sumatriptan and 77 with placebo. The responder rates at 30 minutes were 57% for sumatriptan and 26% for placebo (p = 0.002). Pain-free rates at 30 minutes were 47% for sumatriptan and 18% for placebo (p = 0.003). Sumatriptan was also superior to placebo considering initial response, meaningful relief, and relief of associated symptoms. There were no serious adverse events.\n Sumatriptan nasal spray is effective and well tolerated in the acute treatment of cluster headache attacks of at least 45 minutes' duration.", "Attacks of cluster headache are difficult to treat. Sumatriptan, an agonist of 5-hydroxytryptamine1-like receptors, has proved effective in the treatment of migraine. The clinical similarities between migraine and cluster headache and positive results from an open pilot study in patients with cluster headache indicated that sumatriptan should be evaluated more rigorously in the treatment of this condition.\n We conducted a randomized, double-blind, placebo-controlled crossover study to assess the efficacy and tolerability of sumatriptan in 49 patients with cluster headache. The patients received, in random order, a subcutaneous injection of 6 mg of sumatriptan for one cluster-headache attack and placebo for another attack. The results for the two attacks could be fully evaluated for 39 patients. A response to treatment was defined as complete or almost complete relief of headache (no pain or mild pain) within 15 minutes after the injection.\n In the 39 patients, the severity of headache decreased in 74 percent of the attacks within 15 minutes of treatment with sumatriptan, as compared with 26 percent of the attacks for which placebo was given (P less than 0.001). Thirty-six percent of the patients were free of pain within 10 minutes after the administration of sumatriptan, as compared with 3 percent after placebo (P less than 0.001); by 15 minutes these numbers had increased to 46 percent and 10 percent, respectively (P less than 0.001). Thirteen percent of the patients required oxygen as an additional treatment 15 minutes after receiving sumatriptan, as compared with 49 percent of those who received placebo. The severity of functional disability and the incidence of ipsilateral conjunctival injection also decreased more in response to sumatriptan than placebo. Sumatriptan was well tolerated, and there were no serious adverse events.\n Sumatriptan is an effective and well-tolerated treatment for acute attacks of cluster headache.", "This multicentre, double-blind, randomised, crossover study compared the efficacy, safety and tolerability of subcutaneous sumatriptan (6 mg and 12 mg) with placebo in 134 in-patients with cluster headache. Headache improvement to mild or no pain at 5, 10 and 15 min after treatment was recorded. At 10 min, headache relief was reported by 25% (placebo), 49% (6 mg) and 63% (12 mg) of patients and at 15 min the results were 35% (placebo), 75% (6 mg) and 80% (12 mg) (p < 0.001 for all comparisons with placebo). The 12 mg dose was not significantly better than the 6 mg dose and was associated with more adverse events. The 6 mg dose is therefore recommended for the acute treatment of cluster headache." ]

[ "17306703", "16044026", "18760492", "11401110", "17161060", "18371487", "18195176", "17681958", "18525396" ]

[ "Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial.", "Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation.", "Effects of eythropoietin administration on mitral regurgitation and left ventricular remodeling in heart failure patients.", "The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study.", "Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia.", "Effects of darbepoetin alpha on right and left ventricular systolic and diastolic function in anemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.", "Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.", "Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia.", "Effects of darbepoetin-alpha on quality of life and emotional stress in anemic patients with chronic heart failure." ]

[ "This study sought to investigate whether darbepoetin alfa, an erythropoiesis-stimulating protein (ESP), improves exercise capacity in patients with symptomatic chronic heart failure (CHF) and anemia.\n Anemia is common in patients with CHF.\n In a multicenter, randomized, double-blind, placebo-controlled study, CHF patients with anemia (hemoglobin > or =9.0 to < or =12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 microg/kg every 2 weeks for 26 weeks. The primary end point was change in exercise tolerance from baseline to week 27 as measured by peak oxygen uptake (ml/min/kg body weight). Other end points included changes in absolute peak VO2 (ml/min), exercise duration, and health-related quality of life.\n Differences (95% confidence interval) in mean changes from baseline to week 27 between treatment groups were 1.5 g/dl (0.5 to 2.4) for hemoglobin concentration (p = 0.005), 0.5 ml/kg/min (-0.7 to 1.7) for peak VO2 (p = 0.40), 45 ml/min (-35 to 127) for absolute peak VO2 (p = 0.27), and 108 s (-11 to 228) for exercise duration (p = 0.075). Patients receiving darbepoetin alfa compared with placebo had an improvement in self-reported Patient's Global Assessment of Change (79% vs. 41%, p = 0.01) but no significant differences in the Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores. Darbepoetin alfa was well tolerated.\n In patients with symptomatic CHF and anemia, darbepoetin alfa increased and maintained hemoglobin concentrations and improved health-related quality of life. A trend toward increased exercise time but not peak VO2 was observed. (Impact of Darbepoetin Alfa on Exercise Tolerance and Left Ventricular Structure in Subjects With Symptomatic Congestive Heart Failure (CHF) and Anemia; http://clinicaltrials.gov/ct/show/NCT00117234?order = 1; NCT00117234).", "In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobin<or=12.5 g/dL) in 2 randomized, double-blind, placebo-controlled studies. Subcutaneous (SC) and intravenous administration of 0.75 microg/kg of darbepoetin alfa were compared in a crossover study. The second study compared 2.0, 3.0, and 5.0 microg/kg SC doses with placebo. Darbepoetin alfa (0.75 microg/kg SC) pharmacokinetics were similar in CHF patients and healthy subjects, with a mean (+/-SD) bioavailability of 29 (+/-11)% and 37 (+/-8)%, respectively. In anemic CHF patients, mean (+/-SD) increases in hemoglobin at 4 weeks after the second monthly dose of 2.0, 3.0, and 5.0 microg/kg (SC) of darbepoetin alfa were 2.3 (+/-0.6), 1.4 (+/-1.0), and 2.4 (+/-1.9) g/dL, respectively. Darbepoetin alfa 0.75 microg/kg (SC) given twice, 1 month apart, was insufficient to increase hemoglobin in this study. No severe, drug-related adverse events occurred. Darbepoetin alfa administered once monthly elevates and maintains the hemoglobin concentration in patients with CHF and anemia.", "The effects of erythropoietin administration on mitral regurgitation in patients with congestive heart failure have not yet been examined. After 2 months, erythropoietin treatment results in a significant reduction in left ventricular volumes and mitral regurgitation severity and improves hemodynamics.\n Copyright 2008 Elsevier Ireland Ltd. All rights reserved.", "This is a randomized controlled study of anemic patients with severe congestive heart failure (CHF) to assess the effect of correction of the anemia on cardiac and renal function and hospitalization.\n Although mild anemia occurs frequently in patients with CHF, there is very little information about the effect of correcting it with erythropoietin (EPO) and intravenous iron.\n Thirty-two patients with moderate to severe CHF (New York Heart Association [NYHA] class III to IV) who had a left ventricular ejection fraction (LVEF) of < or =40% despite maximally tolerated doses of CHF medications and whose hemoglobin (Hb) levels were persistently between 10.0 and 11.5 g% were randomized into two groups. Group A (16 patients) received subcutaneous EPO and IV iron to increase the level of Hb to at least 12.5 g%. In Group B (16 patients) the anemia was not treated. The doses of all the CHF medications were maintained at the maximally tolerated levels except for oral and intravenous (IV) furosemide, whose doses were increased or decreased according to the clinical need.\n Over a mean of 8.2+/-2.6 months, four patients in Group B and none in Group A died of CHF-related illnesses. The mean NYHA class improved by 42.1% in A and worsened by 11.4% in B. The LVEF increased by 5.5% in A and decreased by 5.4% in B. The serum creatinine did not change in A and increased by 28.6% in B. The need for oral and IV furosemide decreased by 51.3% and 91.3% respectively in A and increased by 28.5% and 28.0% respectively in B. The number of days spent in hospital compared with the same period of time before entering the study decreased by 79.0% in A and increased by 57.6% in B.\n When anemia in CHF is treated with EPO and IV iron, a marked improvement in cardiac and patient function is seen, associated with less hospitalization and renal impairment and less need for diuretics.", "Anemia is now recognized as being a common finding in CHF and is associated with increased mortality and morbidity. However, it is uncertain whether the anemia is actually causing the worse prognosis or is merely a marker of more severe cardiac disease. Previous intervention studies with subcutaneous (s.c.) beta-EPO in combination with iron have either been uncontrolled or case-controlled studies. We report a randomized, double-blind, placebo-controlled study of the combination of s.c. EPO and oral iron versus oral iron alone in patients with anemia and resistant CHF.\n The present study examines, in patients with advanced congestive heart failure (CHF) and anemia, the effects of beta-erythropoietin (EPO) and oral iron on the anemia and on cardiac and renal functional parameters.\n Forty consecutive subjects with moderate to severe CHF and anemia (hemoglobin [Hb] <11 g/dL) were studied. They were randomized to receive, in a double-blind fashion, either (a) (group A, the treatment group, 20 patients) s.c. beta-EPO for 3 months twice weekly, in addition to daily oral iron, or (b) (group B, the placebo group, 20 patients) normal saline in s.c. injections and daily oral iron. Two patients in group B were eventually excluded because of a fall of Hb <8 g/dL requiring transfusion, leaving 18 patients in group B. After the 3-months study, the group A patients were maintained on the same treatment for an additional 9 months, whereas in Group B, the placebo and oral iron were stopped.\n In group A, after a mean of 3.5 +/- 0.8 months of treatment, there was a significant increase in Hb from 10.4 +/- 0.6 to 12.4 +/- 0.8 g/dL (P < .01); a significant improvement in New York Heart Association functional class from 3.5 +/- 0.6 to 2.8 +/- 0.5 (P < .05); a longer endurance time on exercise testing, from 5.8 +/- 2.2 to 7.8 +/- 2.5 minutes (P < .01); a greater distance walked on exercise testing, from 278 +/- 55 to 356 +/- 88 meters (P < .01); a significant increase in the peak oxygen consumption (VO2) from 12.8 +/- 2.8 to 15.1 +/- 2.8 mL/kg per minute (<.05); and the VO2 at the anaerobic threshold, from 9.2 +/- 2.0 to 13.2 +/- 3.6 mL/kg minute (P < .01). There was also a significant fall in plasma B-type natriuretic peptide levels from 568 +/- 320 to 271 +/- 120 pg/mL (P < .01), a significant reduction in serum creatinine (P < .01), and an increase in estimated creatinine clearance (P < .05). In group B, there were no significant changes in any of the above parameters over the study period. At the end of the 1-year study, the Hb was still higher in group A than group B, and the rate of hospital admissions/patients over the year averaged 0.8 +/- 0.2 in group A and 1.7 +/- 0.8 in group B (P < .01).\n In anemic CHF patients, correction of anemia with EPO and oral iron leads to improvement in New York Heart Association status, measured exercise endurance, oxygen use during exercise, renal function and plasma B-type natriuretic peptide levels and reduces the need for hospitalization.", "Anemia is a frequent condition in chronic heart failure (CHF) that affects adversely long-term cardiac outcomes. We sought to investigate the effects of recombinant human erythropoietin analogue darbepoetin alpha on left (LV) and right ventricular (RV) function and neurohormonal activation in patients with CHF and anemia.\n Thirty-two CHF patients (New York Heart Association class II-III, LV ejection fraction [EF] <40%, hemoglobin level <12.5 g/dL, serum creatinine level <2.5 mg/dL) were randomized (2:1) to receive either a 3-month darbepoetin alpha regimen at 1.5 microg/kg every 20 days plus oral iron (n = 21) or placebo plus oral iron (n = 11). Echocardiographic indices of LV systolic and diastolic function and RV function, plasma B-type natriuretic peptide (BNP) and 6-minute walked distance were assessed at baseline and posttreatment.\n Regarding LV function, only treatment with darbepoetin alpha caused a significant improvement in LVEF (F = 22.001, P < .001), end-systolic wall stress (F = 4.934, P = .034), mitral annulus systolic displacement (F = 6.710, P < .015), isovolumic relaxation time (F = 4.909, P = .035), and E/e ratio (F = 7.833, P = .009). The RV systolic pressure (F = 7.715, P = .009) as well as tricuspid annulus systolic displacement and RVEF (F = 9.264, P = .005) were significantly improved only in the darbepoetin alpha group. Darbepoetin alpha had also alpha beneficial effect on New York Heart Association class (F = 14.586, P = .001), plasma BNP (F = 14.781, P = .001), and 6-minute walk test (F = 19.926, P < .001), whereas these parameters did not significantly change in the placebo-treated patients.\n Darbepoetin alpha improves both LV and RV performance and exercise capacity and counteracts neurohormonal activation in CHF patients with anemia. The drug effects on LV diastolic function, RV function, and LV end-systolic wall stress, in particular, are novel findings, with a potential important contribution to patients' symptomatic improvement.", "Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF.\n Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [-0.2, 1.0] g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > or = 1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups.\n In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed.", "Anaemia is common in chronic heart failure (CHF) and associated with worse outcome. This randomized, double-blind, placebo-controlled study evaluated the effect of two darbepoetin alfa dosing regimens on haemoglobin (Hb) rate of rise and clinical effects in patients with CHF and anaemia.\n Patients with CHF (>or=3 months), left ventricular ejection fraction (LVEF) <or= 40%, and Hb 9.0 to 12.5 g/dL received darbepoetin alfa subcutaneously every 2 weeks for 26 weeks at a starting weight-adjusted dose of 0.75 mcg/kg (n = 56) or a fixed dose of 50 mcg (n = 54), or placebo (n = 55), to gradually achieve and maintain a target Hb of 14.0 +/- 1.0 g/dL. Endpoints included rate of Hb rise per week during titration, safety, and changes in 6 min walk distance, New York Heart Association (NYHA) class, LVEF, and quality of life. Most subjects were NYHA class II-III. Mean (SD) age was 71 (11) years, LVEF was 28 (9), and Hb 11.5 (0.7) g/dL. Rate of Hb rise was equivalent between darbepoetin alfa weight-based (+1.87 +/- 1.36 g/dL) and fixed dosing (+1.64 +/- 0.98 g/dL) groups, vs. + 0.07 +/- 1.08 g/dL in the placebo group. Mean Hb concentrations by week 27 were 13.4 and 13.2 g/dL, in the weight-based and fixed dosing groups, respectively. There were non-significant improvements in the combined darbepoetin alfa group vs. placebo for 6 min walk distance (P = 0.074) and Patient's Global Assessment score (P = 0.057). There was a significant improvement in Kansas City Cardiomyopathy Questionnaire total symptom score (8.2 vs. 1.5 points; P = 0.027) but no change in NYHA class, LVEF, and Minnesota Living With Heart Failure Questionnaire score. Six treatment-unrelated deaths occurred in the 110 darbepoetin alfa treated patients, and none in the 55 placebo treated patients. Other adverse events were similar between groups.\n In this study of patients with CHF and anaemia, treatment with darbepoetin alfa raised Hb using different dosing regimens. Darbepoetin alfa improved some quality of life indices, but its safety requires further exploration. Larger trials are needed to determine the effects on long-term morbidity and mortality.", "Anemia is a frequent comorbidity in chronic heart failure (CHF) adversely affecting patients' prognosis. Erythropoietin seems to improve exercise capacity in CHF patients. This study investigates the effects of recombinant human erythropoietin analog darbepoetin-alpha on quality of life and emotional stress, evaluated by relevant questionnaires in patients with CHF and anemia.\n Forty-one CHF patients [New York Heart Association class: II-III; left ventricular (LV) ejection fraction (EF)<40%; hemoglobin<12.5 g/dl; serum creatinine<2.5 mg/dl] were randomized (1:1) to receive either 3-month darbepoietin-alpha at 1.5 microg/Kg every 20 days plus iron orally (n=21) or placebo plus iron orally (n=20). Echocardiographic LVEF, questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire, functional and overall, Duke's Activity Status Index) and emotional stress [Zung self-rating depression scale (SDS), Beck Depression Inventory], as well as plasma b-type natriuretic peptide and 6-min walking distance (6MWT as a marker of exercise capacity) were assessed at baseline and posttreatment.\n A significant improvement in LVEF (32+/-6 from 26+/-6%, P<0.001), 6MWT (274+/-97 from 201+/-113 m, P<0.01), hemoglobin (12.8+/-1.4 from 10.9+/-1.0 g/dl, P<0.001) and plasma b-type natriuretic peptide (517+/-579 from 829+/-858 pg/ml, P=0.002) was observed posttreatment only in darbepoetin-treated group. Kansas City Cardiomyopathy Questionnaire functional (78+/-14 from 57+/-24%, P<0.01) and overall (68+/-20 from 47+/-22, P<0.001), Duke's Activity Status Index (19+/-11 from 14+/-9, P<0.05), Zung SDS (38+/-10 from 47+/-11, P<0.05) and Beck Depression Inventory (11+/-9 from 16+/-10, P<0.05) scores also improved in darbepoetin-treated patients, whereas they remain unchanged in the placebo group except for the Zung SDS which worsened (P<0.05). A significant correlation between drug-induced percent changes in 6MWT and Zung SDS (r=-0.627, P<0.05) was also observed.\n Darbepoetin-alpha improves quality of life and emotional stress in CHF patients with anemia, with a parallel increase in exercise capacity." ]

[ "7865703", "1754607", "540525", "3790634", "786310", "2694229", "3893272", "6415738", "1808500", "3302738", "3549872", "2388639", "3899033", "331549", "6994907", "8437693", "785952" ]

[ "Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment.", "Piracetam in elderly motorists.", "Piracetam in chronic brain failure.", "Lecithin and piracetam in Alzheimer's disease.", "[On the dose-effect relationship in the therapy with piracetam (author's transl)].", "Can the pattern of neuropsychological improvement obtained with cholinergic drugs be used to infer a cholinergic mechanism in other nootropic drugs?", "Clinical evaluation of compounds for the treatment of memory dysfunction.", "Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment.", "[The significance of quantified EEG in Alzheimer's disease. Changes induced by piracetam].", "[Nootropic drugs: effects and effectiveness. A reflection exemplified by a phase III study using piracetam].", "Piracetam in alcoholic organic mental disorder: a placebo controlled study comparing two dosages.", "A controlled trial of piracetam in intellectually impaired patients with Parkinson's disease.", "Haemorheological pattern in initial mental deterioration: results of a long-term study using piracetam and pentoxifylline.", "[Effect of piracetam on the brain-organic psychosyndrome in cerebrovascular insufficiency. Results of a double-blind study in 40 cases].", "[Clinical experience with treatment by piracetam in gerontopsychiatry (author's transl)].", "Long-term and high-dose piracetam treatment of Alzheimer's disease.", "Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals." ]

[ "A double-blind randomized trial was performed involving 162 patients with age-associated memory impairment (AAMI) selected and followed by their general practitioners. Two intervention methods--a drug and a cognitive therapy--were assessed in combination. Three randomized parallel groups of 54 patients each, aged 55 years and over, were followed and treated for 3 months. After a placebo wash-out period of 10 days, one group received 2.4 g of piracetam, another group, 4.8g, and the third, a placebo. A total of 135 patients, 45 in each group, completed the study. Combined therapy was most effective in patients whose baseline performance on memory tests was lowest. The best results were observed with 4.8 g of piracetam, especially when training sessions began after 6 weeks of drug treatment. This result was confirmed by the global impression of the principal investigator.", "101 elderly motorists with reduced reaction capacity were examined under real traffic conditions with regard to their driving ability. They were given a daily dose of 4.8 g piracetam or placebo over a six-week period in a randomised double-blind study. The percentage of correctly solved sign-observance items, which reflects orientation and perception in real traffic conditions, increased in the placebo-treated test-group from 79.86% in the pretest to 80.07% in the retest, whereas the test subjects of the piracetam-treated group improved their performance from 77.08% to 84.16%. After being treated with piracetam for 6 weeks, the drivers showed a significantly better performance than the placebo-group. Of particular interest is the finding that the test-subjects who had scored less than 80% in the pretest improved without exception in the retest after treatment with piracetam.", "A double-blind, placebo-controlled trial was carried out on 109 aged patients with minimal or with moderate chronic brain failure to assess the effectiveness of piracetam (2.4 g per day) in preventing the progression of dementia. Patients received piracetam or placebo each for 6 weeks, the order of treatment being at random. The results of 19 psychological tests, repeated at 6-weekly intervals, showed that piracetam produced statistically significant improvement in only one of them and then only during the first 6 weeks of treatment. These findings, therefore, do not support the usefulness of piracetam in the treatment of such patients.", "nan", "The effect of piracetam therapy with different dosages was studied in a double blind trial against placebo on its effect in psychoorganic syndrome of old age. 78 patients (61 females, 17 males) on the average of 73.2 years, showed statistically significant differences between piracetam therapy at a dosage of 3 X 1600 mg per day und placebo after a six week peroral therapy while no statistically significant differences between piracetam therapy at a dosage of 3X800 mg per day and placebo were found.", "1. Enhancement of episodic memory and reduction of intrusion errors are considered as the most characteristic outcome of cholinergic drugs administration in AD patients. 2. Since the nootropic drugs Piracetam and Oxiracetam are deemed to act through a cholinergic mechanism, we checked whether AD patients treated with these drugs would show the same pattern of neuropsychological improvement. 3. Results were negative, since (a) episodic memory showed a similar degree of improvement both in patients treated with these drugs and in patients treated with placebo; (b) the number of intrusions tended to increase, rather than to decrease, after the treatment period.", "nan", "In a 12-week double-blind study, piracetam at two dose levels (2.4 and 4.8 g/day) was compared to placebo in the treatment of 60 elderly psychiatric patients with mild diffuse cerebral impairment, but no signs of focal brain lesion. The psychiatric illness, schizophrenia or affective disorder, of patients selected was in remission at the time of the study. Monthly evaluations by the nurse revealed that piracetam improved overall functioning, particularly alertness, socialization, and cooperation, relative to the control group. Patients treated with 2.4 g/day piracetam also showed significant improvement in scores for the full IQ and the memory quotient on the Wechsler Adult Intelligence and Memory Scales; greater response was seen in those with lower initial scores. Piracetam at 4.8 g/day had a more rapid onset of action on behavioral variables than 2.4 g/day, but its therapeutic effect tended to diminish at 12 weeks, possibly as the result of overstimulation. Piracetam did not appear to interfere with concomitant psychotropic maintenance medication or affect the psychiatric illness itself.", "One study was performed in 12 patients with presenile Alzheimer's disease (group I), the other one in 16 patients with mild senile dementia of Alzheimer type (group II). In each study, patients were divided into two randomized parallel groups, one receiving placebo, the other piracetam (9 g daily in group I piracetam and 2.4 g daily in group II piracetam) during three months, piracetam induced a decrease in EEG power on the 2-6 Hz range (group I piracetam), 3-5 Hz and 7 Hz (group II piracetam) and an increase of EEG power in the 9-11 Hz range (group I piracetam) and in the 10 Hz and 13 Hz frequencies (group II piracetam). There was also a significant improvement in the Trail Making Test part A in group II piracetam. Correlations between decreased EEG low frequency components and improvement in some psychometric tests were found significant in the two groups. It seems that the main effect of piracetam was to induce increased alertness. The same results were found in both studies; the good reproducibility suggests that EEG spectral analysis is a reliable tool in the assessment of psychotropic drug effects.", "nan", "The following paper presents an investigation of the efficacy of piracetam in alcoholic organic mental disorder. A double-blind placebo-controlled study design was used to compare 2 dosages of the substance (2 X 3 g vs. 2 X 12 g). Cognitive function was assessed on days 0, 7, 14, 28, 42. Analysis of the results from 24 patients showed a clear-cut amelioration of cognitive functions in all 3 treatment groups. No difference could be demonstrated between the administration of placebo and the lower dose of piracetam. Patients on the higher dose showed an earlier improvement on one of the tests, but the final scores were similar in all three treatment groups.", "Twenty patients with Parkinson's disease and marked intellectual impairment or dementia participated in a double-blind placebo controlled trial of the nootropic, piracetam. A standardized neurological examination, a neuropsychological test battery, and a functional scale, The Sickness Impact Profile, were completed for all patients. They were then assigned by blind randomization to drug or placebo conditions receiving 3.2 g of piracetam or an identical amount of placebo for 12 weeks. The dose was increased to 4.8 g for an additional 12 weeks. Neurological, psychological, and functional measures were rated as improved, unchanged, or worsened in comparison to baseline performance. Twenty-five percent of the patients did not complete the trial for reasons unrelated to the medication. Although there was a significant improvement on one subtest of the functional scale, no significant effects were demonstrated in cognitive or neurological measures.", "A group of 80 elderly subjects affected with recent onset (less than 6 mth) slight to moderate mental deterioration was observed before and after oral drug treatment for a period of 28 wk. The study consisted of four randomized groups of subjects homogeneous for age, sex and life habits. The first group received a placebo, the second group received piracetam (1600 mg 3 times a day), the third group received pentoxifylline (400 mg 3 times a day), and the fourth group received a combination of piracetam and pentoxifylline. At the beginning and end of each phase of the study, neuropsychological and haemorheological parameters were evaluated in all subjects. The results show that the most evident improvement in psycho-intellectual performance, associated with an increase of whole blood filtration values, was obtained in the group treated with the two-drug combination.", "nan", "nan", "Preclinical research suggests that piracetam (a nootropic drug) may improve cognitive functions, but previous studies have failed to demonstrate a clear benefit for the treatment of Alzheimer's disease (AD). We report a 1-year, double-blind, placebo-controlled, parallel-group study with a high dose of piracetam (8 g/d per os) in 33 ambulant patients with early probable AD. Thirty subjects completed the 1-year study. No improvement occurred in either group, but our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with AD. The most significant differences concerned the recall of pictures series and recent incident and remote memory. The drug was well-tolerated.", "A double-blind, intra-individual cross-over comparison of the mental performance of 18 aging, non-deteriorated individuals during two 4-week periods of piracetam (1-acetamide-2-pyrrolidone) and placebo administration was performed using conventional and computerized perceptual-motor tasks. In a majority of these tasks the subjects did significantly better when on piracetam than on placebo, a finding consistent with ratings completed by two independent observers. The findings indicate new avenues for the treatment of individuals with reduced mental performance possibly related to disturbed alertness--a neglected group of psychiatric conditions." ]

[ "16953857", "12648967", "12924681", "17053697", "12580681", "11529805", "7936850" ]

[ "Postnatal home visiting for illicit drug-using mothers and their infants: a randomised controlled trial.", "Postnatal home visits in teenage mothers: a randomised controlled trial.", "Enrolling and retaining mothers of substance-exposed infants in drug abuse treatment.", "Three-year developmental outcomes in children with prenatal alcohol and drug exposure.", "Drug-exposed infants and developmental outcome: effects of a home intervention and ongoing maternal drug use.", "Effectiveness of a home intervention for perceived child behavioral problems and parenting stress in children with in utero drug exposure.", "Parenting and early development among children of drug-abusing women: effects of home intervention." ]

[ "Postnatal home-visiting programs for illicit drug-using mothers have reported some success in reducing harms in some areas but there is a lack of data on their impact on breastfeeding and immunisation rates.\n To investigate the effect on breastfeeding, immunisation and parental drug use. The hypothesis was that the outcomes of the home-visiting group (HVG) would be superior to the control group (CG).\n One hundred and fifty-two illicit drug-using women were recruited at 35-40 weeks gestation from King Edward Memorial Hospital, Perth, Western Australia and randomised after delivery to the HVG or the CG. The HVG had eight home visits; the CG had telephone contact at two months and a home visit at six months. The HVG received education and support for parenting, breastfeeding and child development. This was not provided by the research midwives for the CG.\n The main drugs were heroin, amphetamines, cannabis and benzodiazepines. Immunisation rates were similar for each group. Median duration of breastfeeding for the HVG was eight weeks (95% CI, 3.8-12.2); for the CG ten weeks (95% CI, 7.3-12.7). Drug use was reduced during pregnancy but increased by six months post-partum in both groups. The retention rates were: HVG 93%; CG 86%.\n The hypothesis for this study was not supported. Long-term studies are urgently required to assess the effects of parental drug use on infant and child development.", "Teenage pregnancies are associated with negative socioeconomic effects. Our aim was to ascertain whether a postnatal home-visiting service for teenage mothers younger than age 18 years could reduce the frequency of adverse neonatal outcomes and improve knowledge of contraception, breastfeeding, and infant vaccination schedules in this parent group.\n We enrolled 139 adolescents, attending a teenage pregnancy clinic, in a randomised controlled trial. After completing an antenatal questionnaire designed to assess their knowledge of contraception, infant vaccination, and breastfeeding, we assigned participants to either receive five structured postnatal home visits by nurse-midwives (n=65) or not (n=71). Assessment interviews were done 6 months postpartum. Our primary endpoint was unadjusted difference in knowledge between groups, and incidence of predefined adverse neonatal outcomes. Analysis was by intention to treat.\n Three women withdrew before randomisation because of late fetal loss, 11 mothers withdrew because of adverse neonatal outcomes (adverse neonatal outcome was a primary endpoint, but resulted in withdrawal from the study for knowledge outcomes), and one left voluntarily. Follow-up data were, therefore, available for 124 teenagers. Postnatal home visits were associated with a reduction in adverse neonatal outcomes (intervention: 2; control: 9; relative risk 0.24, 95% CI 0.05-1.08), and a significant increase in contraception knowledge (mean difference 0.92, 95% CI 0.32-1.52). However, there was no significant increase in knowledge with respect to breastfeeding or infant vaccination schedules associated with the home visits.\n Postnatal home-visiting services by nurse-midwives reduce adverse neonatal events and improve contraception outcomes, but do not affect breastfeeding or infant vaccination knowledge or compliance.", "This study provided an experimental test of a drug abuse treatment enrollment and retention intervention in a sample of 103 Black mothers of substance-exposed infants. Significantly more women assigned to the Engaging Moms Program enrolled into drug abuse treatment than did women assigned to the control condition (88% vs. 46%). Sixty-seven percent of participants in the Engaging Moms Program received at least 4 weeks of drug abuse treatment compared with 38% of the control women. However, there were no differences between the groups 90 days following treatment entry. Logistic regressions revealed that readiness for treatment predicted both short-term and long-term treatment retention. The Engaging Moms Program has considerable promise in facilitating treatment entry and short-term retention, but it did not influence long-term retention.", "The purpose of this study was to describe the performance of children whose mothers abused alcohol and drugs heavily during pregnancy, using the Bayley Scales of Infant Development Second Edition (BSID-II) at three years, and to examine the effects of study group, prenatal binge alcohol exposure, and prematurity on developmental outcome.\n Children were born to mothers recruited from two large hospitals or through community referral. Hospital recruits were randomly assigned to either a three-year paraprofessional home visitation intervention program (n = 30) or a control group (n = 31). Community recruits were enrolled in the intervention program (n = 35).\n Among all children the mean BSID-II Mental Developmental Index (MDI) was 84.4 (SD = 14.4) and mean Psychomotor Developmental Index (PDI) was 84.1 (SD = 16.9). Box plots of the MDI and PDI scores by study group, maternal prenatal binge alcohol status, and a binary indicator of prematurity suggested an effect of maternal binge drinking on MDI and PDI scores: children of mothers with a history of binge alcohol consumption have, on average, slightly lower scores. We saw no evidence of a systematic effect of the maternal intervention.\n Developmental performance of preschool children exposed to alcohol and drugs prenatally was, on average, substantially lower than expected for age regardless of study group. Although this home visitation intervention has been shown to be effective in helping mothers address a wide spectrum of needs, it is unlikely sufficient to overcome complex developmental risks of children exposed to alcohol and drugs prenatally. The effect of more comprehensive, multidimensional services specifically designed for the children should be investigated within this context.", "To evaluate the effects of a home intervention and ongoing maternal drug use on the developmental outcome of drug-exposed infants.\n Longitudinal randomized cohort study of a home intervention with substance-abusing mothers and their infants. Mother-infant dyads were randomly assigned to a control or intervention group at 2 weeks' post partum. Control families received brief monthly tracking visits. Intervention families received weekly home visits from 0 to 6 months and biweekly visits from 6 to 18 months by trained lay visitors.\n One hundred eight low-income, inner-city, drug-exposed children (control, 54; intervention, 54) who underwent developmental testing at 6, 12, and 18 months post partum and who remained with their biological mothers through 18 months.\n Infant scores from the Bayley Scales of Infant Development (BSID) at 6, 12, and 18 months post partum. Maternal report of drug use during the pregnancy and ongoing drug use through 18 months post partum was assessed.\n In the repeated-measures analyses, intervention infants had significantly higher BSID Mental Developmental Index (MDI) and Psychomotor Developmental Index scores than control infants. Ongoing maternal cocaine and/or heroin use was associated with lower MDI scores. Finally, MDI scores decreased significantly in both groups.\n Ongoing maternal drug use is associated with worse developmental outcomes among a group of drug-exposed infants. A home intervention led to higher BSID scores among drug-exposed infants. However, BSID MDI scores decreased during the first 18 months post partum among inner-city, low-socioeconomic-status infants in the present study.", "To determine if a home-based nurse intervention (INT), focusing on parenting education/skills and caregiver emotional support, reduces child behavioral problems and parenting stress in caregivers of in utero drug-exposed children.\n Randomized clinical trial of a home-based INT.\n Two urban hospital newborn nurseries; homes of infants (the term infant is used interchangeably in this study with the term child to denote those from birth to the age of 36 months); and a research clinic in Baltimore, Md.\n In utero drug-exposed children and their caregivers (N = 100) were examined when the child was between the ages of 2 and 3 years. Two groups were studied: standard care (SC) (n = 51) and INT (n = 49).\n A home nurse INT consisting of 16 home visits from birth to the age of 18 months to provide caregivers with emotional support and parenting education and to provide health monitoring for the infant.\n Scores on the Child Behavior Checklist and the Parenting Stress Index.\n Significantly more drug-exposed children in the SC group earned t scores indicative of significant emotional or behavioral problems than did children in the INT group on the Child Behavior Checklist Total (16 [31%] vs 7 [14%]; P =.04), Externalizing (19 [37%] vs 8 [16%]; P =.02), and Internalizing (14 [27%] vs. 6 [12%]; P =.05) scales and on the anxiety-depression subscale (16 [31%] vs. 5 [10%]; P =.009). There was a trend (P =.06) in more caregivers of children in the SC group reporting higher parenting distress than caregivers of children in the INT group.\n In utero drug-exposed children receiving a home-based nurse INT had significantly fewer behavioral problems than did in utero drug-exposed children receiving SC (P =.04). Furthermore, those caregivers receiving the home-based INT reported a trend toward lower total parenting distress compared with caregivers of children who received SC with no home visits.", "To evaluate the efficacy of home intervention with drug-abusing women on parenting behavior and attitudes, and on children's development.\n A randomized, clinical trial of 60 drug-abusing women recruited prenatally and randomized into an intervention (n = 31) or comparison (n = 29) group. There were no group differences in gestational age, 1-minute Apgar scores, duration of hospital stay, or neonatal abstinence score. Intervention infants were slightly heavier (P = .098) and had slightly lower 5-minute Apgar scores (P = .089). Most mothers were single, African-American, multiparous, and non-high school graduates from low income families. Approximately 40% of the women were human immunodeficiency virus (HIV)-positive, all admitted to either cocaine and/or heroin use, and 62% had a history of incarceration. Intervention and comparison group women did not differ on any background variables.\n All children received primary care in a multidisciplinary clinic. Biweekly home visits were provided by a nurse beginning before delivery and extending through 18 months of life. The intervention was designed to provide maternal support and to promote parenting, child development, the utilization of informal and formal resources, and advocacy.\n Behavioral measures included self-reported ongoing drug abuse, compliance with primary care appointments, and an observation of the child-centered quality of the home (HOME Scale). Parenting attitudes were measured by the Child Abuse Potential Inventory (CAPI) and the Parenting Stress Index. The CAPI was administered before initiating the intervention and the Parenting Stress Index was administered when the children were 3 months of age. Both scales were repeated when the children were 18 months of age. Developmental status was measured with the Bayley Scales of Infant Development administered at 6, 12, and 18 months.\n Repeated measures multivariate analyses of variance were used to examine changes in parenting attitudes and children's development. Analyses of covariance were used to examine compliance with primary care appointments and the quality of the home. Logistic regression was used to examine ongoing drug abuse. Birth weight and maternal education were used as covariates in all analyses. To control for social desirability, the faking-good index of the CAPI was included as a covariate in analyses involving self-report measures.\n Women in the intervention group were marginally more likely to report being drug-free (P = .059) and were compliant with primary care appointments for their children (P = .069). Based on the HOME Scale, women in the intervention group were more emotionally responsive (P = .033) and provided marginally more opportunities for stimulation (P = .065). At 18 months parents reported more normative attitudes regarding parenting and more child-related stress than they had initially, but the differences were not related to intervention status. At 6 months infants in the intervention group obtained marginally higher cognitive scores (P = .099); at 12 and 18 months there were no differences.\n The findings suggest a cautious optimism regarding the efficacy of early home intervention among drug-abusing women in promoting positive behaviors. Subsequent investigations of home intervention should include larger sample sizes and more intensive options." ]

[ "11239311", "7605179", "9327818" ]

[ "A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy.", "Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial.", "The effects of a home exercise program on impairment and health-related quality of life in persons with chronic peripheral neuropathies." ]

[ "To determine the effect of a specific exercise regimen on clinical measures of postural stability and confidence in a population with peripheral neuropathy (PN).\n Prospective, controlled, single blind study.\n Outpatient clinic of a university hospital.\n Twenty subjects with diabetes mellitus and electrodiagnostically confirmed PN.\n Ten subjects underwent a 3-week intervention exercise regimen designed to increase rapidly available distal strength and balance. The other 10 subjects performed a control exercise regimen.\n Unipedal stance time, functional reach, tandem stance time, and score on the activities-specific balance and confidence (ABC) scale.\n The intervention subjects, but not the control subjects, showed significant improvement in all 3 clinical measures of balance and nonsignificant improvement on the ABC scale.\n A brief, specific exercise regimen improved clinical measures of balance in patients with diabetic PN. Further studies are needed to determine if this result translates into a lower fall frequency in this high-risk population.", "A randomized clinical trial on the effects of strength training was performed in myotonic dystrophy (MyD) patients and patients with hereditary motor and sensory neuropathy (HMSN). Training and most measurement tools involved the proximal lower extremity muscles. The participants trained 3 times a week for 24 weeks with weights adapted to their force. Strength was evaluated by isokinetically measured knee torque. Fatiguability was assessed by the time an isometric contraction could be sustained. Functional performance was measured by timed motor performance and by questionnaires on functional performance. Serum myoglobin (Mb) levels were determined to detect changes in muscle fiber membrane permeability. The MyD group included 33 participants, and the HMSN group included 29 participants. Within each diagnostic group, patients were individually matched and subsequently randomized for treatment allocation. In the MyD patients, none of the measurement techniques showed any training effect. Neither were there signs of deterioration caused by the training. In the HMSN group, knee torques increased. Timed motor performance did not change, although the questionnaires showed an improvement on items related to upper-leg function. Mb levels did not change significantly as a result of the training. In conclusion, the MyD group showed neither positive nor negative effects of the training protocol, whereas the training produced a moderate increase in strength and leg-related functional performance in the HMSN group.", "The effects of a home exercise program for persons with chronic peripheral neuropathies (CPN) have not been documented. We compared changes in impairment and health-related quality of life (HRQL) between exercise and control groups, investigated the relationship between HRQL and measures of impairment, and contrasted the HRQL of individuals with CPN to that previously described for the general population.\n Twenty-eight subjects with CPN, aged 23 to 84 years (mean = 56.2, SD = 14.9), completed the study.\n Impairment measures included average muscle score (AMS), handgrip force, walking time, and forced vital capacity. The HRQL instrument measured the eight scales of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the component scales. The exercise group (n = 14) completed a 6-week home exercise program. The control group (n = 14) did not participate in a home exercise program.\n There was an increase in the AMS in the exercise group compared with the control group. No other between-group differences were found. The exercise group improved in scores on the role limitation scales of the SF-36. The AMS and walking time were moderately correlated with the physical function scale of the SF-36 (r = .55 and -.62, respectively). The SF-36 scores of individuals with CPN were lower than scores previously described for the general population.\n The home exercise program appears to be an important component of the treatment of persons with CPN. Compared with the general population, patients with CPN appear to have a lower HRQL, but some areas appear to improve following a home exercise program." ]

[ "11528165", "15995024", "11459901", "8539548", "9014908", "8782169", "8559353", "1552913", "21745374" ]

[ "A preliminary, randomized, multicenter study comparing intravenous immunoglobulin, plasma exchange, and immune adsorption in Guillain-Barré syndrome.", "Intravenously administered immunoglobulin in the treatment of childhood Guillain-Barré syndrome: a randomized trial.", "Intravenous immune globulins in patients with Guillain-Barré syndrome and contraindications to plasma exchange: 3 days versus 6 days.", "Intravenous immunoglobulin treatment in children with Guillain-Barre syndrome.", "Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group.", "Sequential treatment of Guillain-Barré syndrome with extracorporeal elimination and intravenous immunoglobulin.", "Pilot trial of immunoglobulin versus plasma exchange in patients with Guillain-Barré syndrome.", "A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. Dutch Guillain-Barré Study Group.", "Comparison of intravenous immunoglobulin and plasma exchange in treatment of mechanically ventilated children with Guillain Barré syndrome: a randomized study." ]

[ "nan", "To determine the optimal treatment for childhood Guillain-Barré syndrome (GBS).\n We performed a randomized, multicenter study of GBS according to international diagnostic criteria. In study 1 (early treatment), children able to walk unaided for 5 meters were randomized for 1 g/kg intravenously administered immunoglobulin (IVIG) over 2 days or no treatment. The primary outcome measure was the degree of disability at nadir. In study 2 (treatment for severe GBS), children unable to walk 5 meters unaided were randomized for 1 g/kg IVIG over 2 days or 0.4 g/kg IVIG over 5 days. The primary outcome measure was the number of days needed to regain the ability to walk unaided. Children randomized for no treatment in study 1 could enter study 2 if loss of unaided walking occurred.\n Ninety-five children with GBS were registered in 40 months. Twenty-one children were randomized in study 1 and 51 in study 2 (5 after deterioration in study 1). Twenty-eight children were not randomized for various reasons. Eleven of 21 patients in study 1 lost the ability to walk unassisted and 6 were bedridden, with no statistically significant difference between the children initially randomized for treatment versus no treatment. Recovery occurred faster in the group randomized for early treatment. In study 2, recovery did not differ significantly between the children treated for 2 days versus 5 days (median time to unaided walking: 19 days vs 13 days). Secondary transient deterioration in the disability score occurred more frequently in the group with the 2-day regimen than in the group treated for 5 days (5 of 23 patients vs 0 of 23 patients). Multivariate analysis with Cox regression showed that disease severity at the nadir was the only prognostic factor for recovery.\n Treatment with IVIG before loss of unaided walking did not give rise to a less severe course, but recovery occurred somewhat faster. However, given the small number of patients, the power of this conclusion is low. For treatment after loss of unaided walking, there was no significant difference in the effectiveness of 2 g/kg IVIG administered over 2 days versus 5 days. Early \"relapses\" occurred more frequently after the shorter treatment regimen.", "Plasma exchange is contraindicated in 10 to 20% of patients with Guillain-Barré syndrome (GBS). The optimal schedule for intravenous immune globulin (IVIg) therapy has not yet been established in these patients. The objective was to compare the efficacy and safety of two IVIg treatment durations in patients with GBS with contraindications for plasma exchange. In this randomised, double blind, multicentre phase II trial conducted in seven French centres, patients with GBS with severe haemostasis, unstable haemodynamics, or uncontrolled sepsis were randomly assigned to 0.4 g/kg/day IVIg for 3 or 6 days. The primary outcome measure was the time needed to regain the ability to walk with assistance. Thirty nine patients were included from March 1994 to May 1997, 21 in the 3 day group and 18 in the 6 day group. Time to walking with assistance was non-significantly shorter in the 6 day group (84 (23-121) v 131 days (51-210), p=0.08); the difference was significant in ventilated patients (86 days (13-151) in the 6 day group v 152 days (54-332) in the 3 day group; p=0.04). The prevalence and severity of IVIg related adverse effects were comparable between the two groups. In conclusion, in patients with GBS and contraindications for plasma exchange, especially those who need ventilatory assistance, IVIg (0.4 g/kg/day) may be more beneficial when given for 6 days rather than 3 days.", "Guillain-Barre syndrome is an acquired demyelinating polyneuropathy that is presumed to be immune-mediated. On the basis of this assumption, intravenous immunoglobulin (IVIG) has been used in the treatment of Guillain-Barre syndrome in recent years and found to be effective. To test this we performed a randomized study in patients with Guillain-Barre syndrome by giving IVIG (1 g/kg body weight per day over 2 consecutive days) in 9 children who were compared with 9 patients who were observed but not given specific therapy. We concluded that intravenous immunoglobulin is a safe and effective treatment for childhood Guillain-Barre syndrome which shortens the time to recovery.", "The relative efficacy of plasma exchange (PE) and intravenous immunoglobulin (IVIg) for the treatment of Guillain-Barré syndrome has not been established. We compared PE with IVIg, and with a combined regimen of PE followed by IVIg, in an international, multicentre, randomised trial of 383 adult patients with Guillain-Barré syndrome.\n The patients were randomly assigned PE (five 50 mL/kg exchanges over 8-13 days), IVIg (Sandoglobulin, 0.4 g/kg daily for 5 days), or the PE course immediately followed by the IVIg course. The inclusion criteria were severe disease (aid needed for walking) and onset of neuropathic symptoms within the previous 14 days. Patients were followed up for 48 weeks.\n Four patients were excluded because they did not meet the randomisation criteria. All the remaining 379 patients were assessed for the major outcome criterion-change on a seven-point disability grade scale-by an observer unaware of treatment assignment, 4 weeks after randomisation. At that time, the mean improvement was 0.9 (SD 1.3) in the 121 PE-group patients, 0.8 (1.3) in the 130 IVIg-group patients, and 1.1 (1.4) in the 128 patients who received both treatments (intention-to-treat analysis). None of the differences between the groups for this major outcome criterion was significant. The difference between PE alone and IVIg alone was so small that a 0.5 grade difference was excluded at the 95% level of confidence. There was no significant difference between any of the treatment groups in the secondary outcome measures: time to recovery of unaided walking, time to discontinuation of ventilation, and trend describing the recovery from disability up to 48 weeks. There was a non-significant trend towards a more favourable outcome on some outcome measures with combined treatment.\n In treatment of severe Guillain-Barré syndrome during the first 2 weeks after onset of neuropathic symptoms, PE and IVIg had equivalent efficacy. The combination of PE with IVIg did not confer a significant advantage.", "Plasma exchange (PE) and administration of intravenous immunoglobulin (IgG) are established treatments for Guillain-Barré syndrome (GBS). Elimination of postulated pathogenetic factors by plasma exchange or similar methods, such as selective adsorption (SA) treatment using affinity-type adsorption columns and subsequent immunomodulation by intravenous IgG, may provide a more effective treatment. Forty-five patients with acute GBS were prospectively examined using a clinical score. We treated 11 patients by plasma exchange, 13 with selective adsorption using a tryptophan-linked polyvinyl alcohol gel adsorbent, and a group of 21 patients by selective adsorption followed by intravenous IgG. The patients treated sequentially by selective adsorption and intravenous IgG improved significantly better than the patients who received plasma treatment only. This pilot study suggests that sequential treatment of GBS may be superior to plasma treatment alone. The higher cost of this combined treatment might be offset by shorter hospital stays and lower overall expenditure. The preliminary results warrant further investigation in a multicenter trial.", "We compared intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) in the treatment of 50 patients with Guillain-Barré syndrome (GBS). Standard outcome measures did not differ for the two groups. Sixty-one percent of the PLEX-treated group and 69% of the IVIG-treated group improved by one disability grade at 1 month. The complication rate was higher in the PLEX-treated group. We conclude that the efficacy of IVIG in the treatment of GBS is comparable with that of PLEX and that it can be used safely, although we had a small number of patients. We did not observe a higher relapse rate with IVIG. The usefulness of combination therapy is unknown at this time.", "The subacute demyelinating polyneuropathy known as Guillain-Barré syndrome improves more rapidly with plasma exchange than with supportive care alone. We conducted a multicenter trial to determine whether intravenous immune globulin is as effective as the more complicated treatment with plasma exchange.\n To enter the study, patients had to have had Guillain-Barré syndrome for less than two weeks and had to be unable to walk independently. They were randomly assigned to receive either five plasma exchanges (each of 200 to 250 ml per kilogram of body weight) or five doses of a preparation of intravenous immune globulin (0.4 g per kilogram per day). The predefined outcome measure was improvement at four weeks by at least one grade on a seven-point scale of motor function.\n After 150 patients had been treated, strength had improved by one grade or more in 34 percent of those treated with plasma exchange, as compared with 53 percent of those treated with immune globulin (difference, 19 percent; 95 percent confidence interval, 3 percent to 34 percent; P = 0.024). The median time to improvement by one grade was 41 days with plasma exchange and 27 days with immune globulin therapy (P = 0.05). The immune globulin group had significantly fewer complications and less need for artificial ventilation.\n In the acute Guillain-Barré syndrome, treatment with intravenous immune globulin is at least as effective as plasma exchange and may be superior.", "Respiratory failure is a life threatening complication of Guillain Barré syndrome (GBS). There is no consensus on the specific treatment for this subset of children with GBS.\n This was a prospective randomized study to compare the outcome of intravenous immunoglobulin (IVIG) and plasma exchange (PE) treatment in children with GBS requiring mechanical ventilation. Forty-one children with GBS requiring endotracheal mechanical ventilation (MV) within 14 days from disease onset were included. The ages of the children ranged from 49 to 143 months.Randomly, 20 children received a five-day course of IVIG (0.4 g/kg/day) and 21 children received a five-day course of one volume PE daily. Lumbar puncture (LP) was performed in 36 patients (18 in each group).\n Both groups had comparable age (p = 0.764), weight (p = 0.764), duration of illness prior to MV (p = 0.854), preceding diarrhea (p = 0.751), cranial nerve involvement (p = 0.756), muscle power using Medical Research Council (MRC) sum score (p = 0.266) and cerebrospinal fluid (CSF) protein (p = 0.606).Children in the PE group had a shorter period of MV (median 11 days, IQR 11.0 to 13.0) compared to IVIG group (median 13 days, IQR 11.3 to 14.5) with p = 0.037.Those in the PE group had a tendency for a shorter Pediatric Intensive Care Unit (PICU) stay (p = 0.094).A total of 20/21 (95.2%) and 18/20 (90%) children in the PE and IVIG groups respectively could walk unaided within four weeks after PICU discharge (p = 0.606).There was a negative correlation between CSF protein and duration of mechanical ventilation in the PE group (p = 0.037), but not in the IVIG group (p = 0.132).\n In children with GBS requiring MV, PE is superior to IVIG regarding the duration of MV but not PICU stay or the short term neurological outcome.The negative correlation between CSF protein values and duration of MV in PE group requires further evaluation of its clinical usefulness.\n Clinicaltrials.gov Identifier NCT01306578." ]

[ "17669279", "16773321", "16963360", "12233274", "12473698", "16818967", "11314793", "10418861", "10463751", "18804577" ]

[ "Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.", "[Cost-benefit analysis of the use of rhBMP-2 in open tibial fractures: savings from a health insurer's perspective].", "An ongoing research for evaluation of treatment with BMPs or AGFs in long bone non-union: protocol description and preliminary results.", "Healing of fresh tibial fractures with OP-1. A preliminary report.", "Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.", "Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial.", "Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions.", "Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites.", "Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect.", "A comparison of RhBMP-7 (OP-1) and autogenous graft for metaphyseal defects after osteotomy of the distal radius." ]

[ "To assess the clinical effectiveness and cost-effectiveness of bone morphogenetic protein (BMP) for the treatment of spinal fusions and the healing of fractures compared with the current standards of care.\n Electronic databases, related journals and references from identified studies were searched in January 2006, with an updated search only for randomised controlled trials (RCTs) in November 2006.\n A systematic review of available data was conducted. The data from selected studies were then analysed and graded according to quality and processed to give a value to the efficacy of BMP. Existing models were modified or updated to evaluate the cost-effectiveness of BMP for open tibial fractures and spinal fusion.\n All selected trials were found to have several methodological weaknesses. Insufficient sample size in most trials, meant that patient baseline comparability between trial arms was not achieved and the statistical power to detect a moderate effect was low. Data did indicate that BMP increased fracture union among patients with acute tibial fractures and found that high-dose BMP is more effective than a lower dose for open tibial fractures. The healing rate in the BMP group was not found to be statistically significantly different from that in the autogenous bone grafting group for patients with tibial non-union fractures, but BMP reduced the number of secondary interventions in patients with acute tibial fractures compared with controls. There was very limited evidence that BMP in scaphoid non-union was safe and may help to accelerate non-union healing when used in conjunction with either autograft or allograft. There was evidence that BMP-2 is more effective than autogenous bone graft for radiographic fusion in patients with single-level degenerative disc disease. No significant difference was found when BMP-7 was compared with autograft for degenerative spondylolisthesis with spinal stenosis and spondylolysis. The use of BMP was associated with a reduced operating time, improvement in clinical outcomes and a shorter hospital stay as compared with autograft. The proportion of secondary interventions tended to be lower in the BMP group than the control, but not of statistical significance. Trial data on time to return to work postoperatively were sometimes difficult to interpret because of unclear or inappropriate data analysis methods. The incremental cost of BMP for open tibial fractures was estimated to be about 3.5 million pounds per year in the UK. The estimated incremental cost per quality-adjusted life-year (QALY) gained is 32,603 pounds. The probability that cost per QALY gained is less than 30,000 pounds for open tibial fracture is 35.5%. The cost-effectiveness ratio is sensitive to the price of BMP and the severity of open tibial fractures. The use of recombinant human bone morphogenetic protein for spinal fusion surgery may increase the cost to the UK NHS by about 1.3 million pounds per year. The estimated incremental cost per QALY gained was about 120,390 pounds. The probability that BMP is cost-effective (i.e. cost/QALY less than 30,000 pounds) was only 6.4%. From the societal perspective, the estimated total cost of using BMP for spinal fusion is about 4.2 million pounds per year in the UK.\n Additional BMP treatment plus conventional intervention is more effective than conventional intervention alone for union of acute open tibial fractures. The cost-effectiveness of additional BMP may be improved if the price of BMP is reduced or if BMP is mainly used in severe cases. BMP may eliminate the need for autogenous bone grafting so that costs and complications related to harvesting autograft can be avoided. In non-unions, there is no evidence that BMP is more or less effective than bone graft; however, it is currently used when bone graft and other treatments have failed. The use of BMP-2 in spinal fusion surgery seems to be more effective than autogenous bone graft in terms of radiographic spinal fusion among patients with single-level degenerative disc disease. There is a lack of evidence about the effectiveness of BMP for other spinal disorders including spondylolisthesis and spinal stenosis. There was limited evidence showing that BMP is associated with greater improvement in clinical outcomes. According to the results of economic evaluation, the use of BMP for spinal fusion is unlikely to be cost-effective. The following areas would benefit from further research: clinical trials of BMP that include formal economic evaluation, a multicentre RCT of fracture non-union and of interbody and/or posterolateral spinal fusion, trials of non-tibial acute long bone fractures, and RCTs comparing BMP-2, BMP-7 and controls.", "The purpose of the current study was to evaluate savings from the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in open tibia fractures by faster fracture healing and reduction of secondary treatment costs from a health insurance perspective for Germany and to compare them to the upfront price of 2900 EUR of rhBMP-2.\n Raw data from a previously published study (BESTT study) were used to conduct an economic calculation for secondary treatment costs for each patient from the standard care group and the 1.5 mg/ml rhBMP-2 group based on G-DRG 2005 prices from a health insurer's perspective for an observation period of 1 year for Germany.\n The use of rhBMP-2 leads to savings of 5697 EUR and 3183 EUR per patient for Gustilo-Anderson grade IIIB and all grade IIIA and B injuries, respectively. These savings offset the upfront price of 2900 EUR of rhBMP-2 and, therefore, net savings of 2797 EUR and 283 EUR for grade IIIB and all grade IIIA and B injuries can be achieved, respectively. These savings are mainly due to reduced sickness payments because of faster fracture healing in the rhBMP-2 group.\n The current study shows that the use of rhBMP-2 in Gustilo-Anderson grade IIIA and B open fractures leads--besides the better medical outcome for patients as shown previously in the BESTT study--to net savings from a health insurer's perspective.", "Treatment of long bone non-union (NU) continues to be a challenging task for the trauma surgeon often resulting in unsatisfactory results and long-term morbidity. Whilst autologous bone grafting remains the gold standard of treatment of these difficult cases, recently, due to the advances made in tissue engineering techniques, other alternatives have become available. In this study we report our preliminary results of treating long bone non-unions using either bone morphogenetic protein-7 (BMP-7) or platelet rich plasma (PRP) concentrations. Twenty-nine cases have entered this study thus far. Preliminary results indicate that BMP-7 is more efficacious that PRP as there was a significant failure rate of 6.2% versus 38.5% between BMP-7 and PRP, respectively.", "Osteogenic proteins (OP) are elements of a class of natural growth factors called Bone Morphogenetic Proteins (BMP). A specific member of this class is OP-1, a human recombinant protein that has osteogenic properties. The osteoinductive and osteoconductive properties of OP-1, with its specific collagen matrix, promote the generation of new functionally active, biologically and biomechanically mature bone. We carried out a clinical study to verify the potential of this protein in fresh tibial closed fractures, using OP-1 associated with osteosynthesis by means of a monolateral external fixator.", "The treatment of open fractures of the tibial shaft is often complicated by delayed union and nonunion. The objective of this study was to evaluate the safety and efficacy of the use of recombinant human bone morphogenetic protein-2 (rhBMP-2; dibotermin alfa) to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention.\n In a prospective, randomized, controlled, single-blind study, 450 patients with an open tibial fracture were randomized to receive either the standard of care (intramedullary nail fixation and routine soft-tissue management [the control group]), the standard of care and an implant containing 0.75 mg/mL of rhBMP-2 (total dose of 6 mg), or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2 (total dose of 12 mg). The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure. Randomization was stratified by the severity of the open wound. The primary outcome measure was the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months postoperatively.\n Four hundred and twenty-one (94%) of the patients were available for the twelve-month follow-up. The 1.50-mg/mL rhBMP-2 group had a 44% reduction in the risk of failure (i.e., secondary intervention because of delayed union; relative risk = 0.56; 95% confidence interval = 0.40 to 0.78; pairwise p = 0.0005), significantly fewer invasive interventions (e.g., bone-grafting and nail exchange; p = 0.0264), and significantly faster fracture-healing (p = 0.0022) than did the control patients. Significantly more patients treated with 1.50 mg/mL of rhBMP-2 had healing of the fracture at the postoperative visits from ten weeks through twelve months (p = 0.0008). Compared with the control patients, those treated with 1.50 mg/mL of rhBMP-2 also had significantly fewer hardware failures (p = 0.0174), fewer infections (in association with Gustilo-Anderson type-III injuries; p = 0.0219), and faster wound-healing (83% compared with 65% had wound-healing at six weeks; p =0.0010).\n The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.", "Currently, the treatment of diaphyseal tibial fractures associated with substantial bone loss often involves autogenous bone-grafting as part of a staged reconstruction. Although this technique results in high healing rates, the donor-site morbidity and potentially limited supply of suitable autogenous bone in some patients are commonly recognized drawbacks. The purpose of the present study was to investigate the benefit and safety of the osteoinductive protein recombinant human bone morphogenetic protein-2 (rhBMP-2) when implanted on an absorbable collagen sponge in combination with freeze-dried cancellous allograft.\n Adult patients with a tibial diaphyseal fracture and a residual cortical defect were randomly assigned to receive either autogenous bone graft or allograft (cancellous bone chips) for staged reconstruction of the tibial defect. Patients in the allograft group also received an onlay application of rhBMP-2 on an absorbable collagen sponge. The clinical evaluation of fracture-healing included an assessment of pain with full weight-bearing and fracture-site tenderness. The Short Musculoskeletal Function Assessment (SMFA) was administered before and after treatment. Radiographs were used to document union, the presence of extracortical bridging callus, and incorporation of the bone-graft material.\n Fifteen patients were enrolled in each group. The mean length of the defect was 4 cm (range, 1 to 7 cm). Ten patients in the autograft group and thirteen patients in the rhBMP-2/allograft group had healing without further intervention. The mean estimated blood loss was significantly less in the rhBMP-2/allograft group. Improvement in the SMFA scores was comparable between the groups. No patient in the rhBMP-2/allograft group had development of antibodies to BMP-2; one patient had development of transient antibodies to bovine type-I collagen.\n The present study suggests that rhBMP-2/allograft is safe and as effective as traditional autogenous bone-grafting for the treatment of tibial fractures associated with extensive traumatic diaphyseal bone loss.\n Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.", "The role of bone morphogenetic proteins (BMPs) in osseous repair has been demonstrated in numerous animal models. Recombinant human osteogenic protein-1 (rhOP-1 or BMP-7) has now been produced and was evaluated in a clinical trial conducted under a Food and Drug Administration approved Investigational Device Exemption to establish both the safety and efficacy of this BMP in the treatment of tibial nonunions. The study also compared the clinical and radiographic results with this osteogenic molecule and those achieved with fresh autogenous bone.\n One hundred and twenty-two patients (with 124 tibial nonunions) were enrolled in a controlled, prospective, randomized, partially blinded, multi-center clinical trial between February, 1992, and August, 1996, and were followed at frequent intervals over 24 months. Each patient was treated by insertion of an intramedullary rod, accompanied by rhOP-1 in a type I collagen carrier or by fresh bone autograft. Assessment criteria included the severity of pain at the fracture site, the ability to walk with full weight-bearing, the need for surgical re-treatment of the nonunion during the course of this study, plain radiographic evaluation of healing, and physician satisfaction with the clinical course. In addition, adverse events were recorded, and sera were screened for antibodies to OP-1 and type-I collagen at each outpatient visit.\n At 9 months following the operative procedures (the primary end-point of this study), 81% of the OP-1-treated nonunions (n = 63) and 85% of those receiving autogenous bone (n = 61) were judged by clinical criteria to have been treated successfully (p = 0.524). By radiographic criteria, at this same time point, 75% of those in the OP-1-treated group and 84% of the autograft-treated patients had healed fractures (p = 0.218). These clinical results continued at similar levels of success throughout 2 years of observation, and there was no statistically significant difference in outcome between the two groups of patients at this point (p = 0.939). All patients experienced adverse events. Forty-four percent of patients in each treatment group had serious events, none of which were related to their bone grafts. More than 20% of patients treated with autografts had chronic donor site pain following the procedure.\n rhOP-1 (BMP-7), implanted with a type I collagen carrier, was a safe and effective treatment for tibial nonunions. This molecule provided clinical and radiographic results comparable with those achieved with bone autograft, without donor site morbidity.", "Osteogenic proteins (OPs), also referred to as bone morphogenetic proteins (BMPs), are a family of bone-matrix polypeptides isolated from a variety of mammalian species. Implantation of osteogenic proteins induces a sequence of cellular events that leads to the formation of new bone. In preclinical studies, the implantation of recombinantly produced human osteogenic protein-1 (OP-1, also referred to as BMP-7) into surgically created, critical-size diaphyseal segmental defects resulted in the regeneration of new bone that was fully functional biologically and biomechanically. Injection of an OP-1 solution into a fresh fracture model accelerated the bone repair process compared with control fracture healing. This was the result of greater and earlier new bone formation. Further study has demonstrated that OP-1 can be used as a bone graft substitute to promote spinal fusion, aid in the incorporation of metal implants, and improve the performance of autograft and allograft bone. Clinical study of OP-1 implanted in conjunction with a bovine bone-derived type 1 collagen carrier for the treatment of tibial nonunion fractures has shown healing characteristics similar to that obtained with autogenous iliac crest bone graft. Advantages of OP-1 included no donor site complications, less blood loss, and a shorter operative time.", "We performed a prospective, randomised double-blind study in 24 patients undergoing high tibial osteotomy to evaluate the effectiveness of human recombinant osteogenic protein (OP-1) on a collagen type-I carrier in a critically-sized fibular defect. The study had two phases, each evaluated by clinical, radiological and DEXA methods during the first postoperative year. The first concerned the validation of the model of the fibular defect, using positive (demineralised bone) and negative (untreated) controls. The second phase concerned the osteogenic potential of OP-1 on collagen type-I v collagen type-I alone. The results of the first phase established the critically-sized nature of the defect. In the untreated group no bony changes were observed while, in the demineralised bone group, formation of new bone was visible from six weeks onwards. The results of the second phase showed no significant formation of new bone in the presence of collagen alone, while in the OP-1 group, all patients except one showed formation of new bone from six weeks onwards. This proved the osteogenic activity of OP-1 in a validated critically-sized human defect.", "SUMMARY AIM: The aim of the study was to demonstrate whether RhBMP-7 is an effective alternative to autogenous bone graft in the healing of metaphyseal defects in the distal radius following corrective osteotomies for symptomatic malunion after distal radial fractures.\n Thirty patients were entered into the study and were randomised to receive either RhBMP-7 or autogenous bone graft harvested from the ipsilateral iliac crest. Stabilisation of the osteotomy was either carried out with non- bridging external fixation or the pi-plate. Clinical, radiographic and functional review were carried out at regular intervals up to 1 year.\n The first 10 patients were treated using non-bridging external fixation of the osteotomy. Two of the 4 patients treated with RhBMP-7 developed excessive osteolysis around the osteotomy site resulting in loss of the corrected position and non-union of the osteotomy. The other 2 patients healed at 13 weeks. The 6 patients treated with autogenous bone graft all healed at an average of 7 weeks, without any complications. It was postulated that the osteolysis was related to instability of the osteotomy site, and the use of external fixation was abandoned and replaced with internal fixation with a dorsal pi-plate. In the pi-plate group of patients, 10 were treated with autogenous bone graft and 10 with RhBMP-7. The bone graft patients healed at 7 weeks compared to 18 weeks for the RhBMP-7 patients, which was statistically significant (p = 0.019). The patients who received bone graft had complete filling of the metaphyseal defect radiologically. Five patients treated with RhBMP-7 healed at the volar cortex with a dorsal defect remaining at 1 year. Two patients developed non-union radiologically. Ten patients (3 in the RhBMP-7 and 7 in the bone graft groups) required plate removal for soft tissue complications.\n RhBMP-7 does not confer the same stability as bone graft, allowing shear forces across the osteotomy site when used in conjunction with non-bridging external fixation, reducing the capacity for healing and resulting in osteolysis. Using the RhBMP-7 with a pi-plate resulted in healing of the osteotomy, but at a slower rate than autogenous bone graft." ]

[ "14620099" ]

[ "Adjunctive treatment of decompression illness with a non-steroidal anti-inflammatory drug (tenoxicam) reduces compression requirement." ]

[ "We report a randomized trial examining adjunctive administration of the NSAID, tenoxicam, to divers suffering with DCI. 180 subjects were graded for severity on admission and randomized according to a stratified random number schedule. Subjects were recompressed and treatment continued daily until symptom stabilization or complete resolution. Tenoxicam 20 mg or a placebo preparation was administered at the first air break during the initial recompression and continued daily for seven days. The subjects were assessed using a recovery status score at the completion of treatment and at 4-6 weeks. The proportion of patients with mild residual symptoms at discharge and final follow-up was not significantly different (discharge placebo 30% versus tenoxicam 37%, P=0.41; six weeks placebo 20% versus tenoxicam 17%, P=0.58). There was a significant reduction in the number of treatments required to achieve discharge (median treatments placebo 3, tenoxicam 2, P=0.01). 61% of patients in the tenoxicam group required less than 3 compressions, versus 40% in the placebo group (P=0.01, RRR 33 % [95%CI 9%-56%], NNT=5 [95%CI 3-18]). There was no evidence of increased complications of treatment in the tenoxicam group. When given this NSAID, patients with DCI require fewer hyperbaric oxygen (HBO2) sessions to achieve a standard clinical end-point and there is likely to be an associated cost saving." ]

[ "14769732", "10459902", "17685853" ]

[ "Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial.", "Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial.", "Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebo-controlled phase 2B trial." ]

[ "The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding the complete human CFTR cDNA. Secondary objectives included evaluation of pulmonary function assessed by spirometry, lung abnormalities by high-resolution CT (HRCT), airway cytokines, vector shedding, serum neutralizing antibody to AAV serotype 2 (AAV2), and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings.\n Randomized, double-blind, placebo-controlled, phase II trial.\n Eight cystic fibrosis (CF) centers in the United States.\n CF patients with mild lung disease, defined as FEV(1) > or =60% predicted.\n Subjects were randomized to inhale three aerosolized doses of 1 x 10(13) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer (PARI; Richmond, VA). Measurements and results: Of 42 subjects randomized, 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo. No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups. Improvements in induced-sputum interleukin-8 (p = 0.03) and FEV(1) (p = 0.04) were observed at day 14 and day 30, respectively, in the group receiving tgAAVCF when compared to those receiving placebo. No significant differences in HRCT scans were noted. Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector. All subjects receiving tgAAVCF exhibited an increase (by at least fourfold) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL. Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy.\n Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.", "We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial.\n Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence.\n Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p<0.05) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence was also reduced. We detected no alterations in the sodium transport abnormality. A similar pattern occurred following nasal administration.\n Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis.", "Previous studies have demonstrated that delivery of a recombinant adeno-associated virus (AAV) vector encoding the complete human cystic fibrosis transmembrane regulator (CFTR) cDNA (tgAAVCF) to the nose, sinus, and lungs of subjects with cystic fibrosis (CF) was safe and well tolerated. In a small randomized, double-blind study of three doses of aerosolized tgAAVCF or placebo at 30-day intervals, encouraging but non-significant trends in pulmonary function and induced sputum interleukin 8 (IL-8) levels were seen at early time points. This larger study was conducted to verify these trends. One hundred and two subjects aged 12 years and older with mild-to-moderate cystic fibrosis (forced expiratory flow in 1 sec [FEV1]:60% predicted) were randomized to two aerosolized doses of 1x10(13)DNase-resistant particles of tgAAVCF (n=51) or matching placebo (n=51) administered 30 days apart. Although tgAAVCF was well tolerated, the study did not meet its primary efficacy end point of statistically significant improvement in FEV1 30 days after initial administration of tgAAVCF compared with placebo. There were no significant differences in spirometric lung function over time, induced sputum biologic markers, or days of antibiotic use in either treatment group. Thus repeated doses of aerosolized tgAAVCF were safe and well tolerated, but did not result in significant improvement in lung function over time. Because gene transfer is the simplest, most basic way to correct the underlying genetic defect that leads to disease in CF, further research is warranted to develop an effective gene transfer agent for the treatment of CF." ]

[ "3057956", "3282825", "3579004", "7551381", "20627502", "12947128", "2651744", "19074931", "2116747", "20188315", "1456568", "12720592", "2368979", "22857881" ]

[ "The effect of supplementary oral nutrition in poorly nourished patients with chronic obstructive pulmonary disease.", "Dietary supplementation and respiratory muscle performance in patients with COPD.", "Nutritional supplementation in ambulatory patients with chronic obstructive pulmonary disease.", "Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. A placebo-controlled randomized trial.", "Effects of nutritional supplementation combined with low-intensity exercise in malnourished patients with COPD.", "Nutritional enhancement of exercise performance in chronic obstructive pulmonary disease: a randomised controlled trial.", "Nutritional repletion in malnourished patients with emphysema.", "Dietary counselling and food fortification in stable COPD: a randomised trial.", "The effects of refeeding on peripheral and respiratory muscle function in malnourished chronic obstructive pulmonary disease patients.", "Efficacy and costs of nutritional rehabilitation in muscle-wasted patients with chronic obstructive pulmonary disease in a community-based setting: a prespecified subgroup analysis of the INTERCOM trial.", "Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study.", "Energy balance in depleted ambulatory patients with chronic obstructive pulmonary disease: the effect of physical activity and oral nutritional supplementation.", "The immune response to short-term nutritional intervention in advanced chronic obstructive pulmonary disease.", "Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD." ]

[ "We carried out a prospective, randomized, controlled trial to investigate the effect of a 3-month period of supplementary oral nutrition in 14 poorly nourished outpatients with COPD. Seven patients were randomized into Group 1 who received their normal diet during Months 1 to 3, a supplemented diet during Months 4 to 6, and their original normal diet during Months 7 to 9. The other 7 patients received their normal diet for the entire 9-month study period (Group 2). Seven well-nourished patients (Group 3) matched for age and severity of air-flow obstruction served as control subjects; they received their normal diet for the 9-month study period. Measurements of nutritional status, respiratory muscle and handgrip strength, sternomastoid muscle function (including frequency/force curves, maximal relaxation rate, and a fatigability test), lung function, arterial blood gas tensions, general well-being and breathlessness scores, and 6-min walking distances were carried out monthly in all patients. At the start of the study, the poorly nourished patients had lower mean daily calorie and protein intakes than did the well-nourished patients. The poorly nourished patients had lower respiratory muscle and handgrip strength, and abnormal contractility and increased fatigability of the sternomastoid muscle compared with those in the well-nourished patients. After 3 months of supplementary oral nutrition, there was a significant improvement in the nutritional status of Group 1 patients, as evidenced by an increase in body weight, triceps skinfold thickness, and midarm muscle circumference. Respiratory muscle and handgrip strength increased in parallel with nutritional status, although there were no significant changes in lung function or arterial blood gas tensions.(ABSTRACT TRUNCATED AT 250 WORDS)", "We studied the effects of oral nutritional supplementation on respiratory muscle (RM) performance in 25 ambulatory patients with severe chronic obstructive pulmonary disease (COPD). There was a relationship between body weight and anthropometric parameters of nutritional status (triceps skinfold thickness [r = 0.67; p less than 0.005], midarm muscle circumference (r = 0.53; p less than 0.005), but body weight did not correlate with daily caloric intake, serum albumin, transferrin, or blood lymphocyte count. None of these measurements of nutritional status correlated with any measure of RM strength or endurance. In a randomized observer-blinded crossover trial, patients were allocated to one of two groups. In the first eight weeks of the study, group A received nutritional supplementation, and patients in group B were control subjects. In the second eight weeks, patients in group A were control subjects, and group B received supplement. Mean daily caloric intake and body weight increased in both groups while receiving supplement (both p less than 0.05). Calories provided by the supplement were frequently substituted for normal dietary calories. Any increases in RM performance in the group receiving supplement were matched by increases (due to learning) in controls. We conclude that oral dietary supplements have no important effects on RM performance in ambulatory patients with COPD.", "We examined the effect of nutritional supplementation for 8 wk on respiratory muscle function (RMF) in 21 malnourished patients with COPD. Patients were randomized to a fed group or to a control group. Patients in the fed group were provided with an enteral formula in addition to their usual diet. Daily calorie and protein intake and weekly anthropometric measures were made. Pulmonary function tests were measured on Weeks 1, 4, and 8. Respiratory muscle strength was measured by means of maximal inspiratory and expiratory pressures (MIP), (MEP), and respiratory muscle endurance was measured by the maximal sustained ventilatory capacity (MSVC). The mean weight of the fed group increased from 52.2 +/- 6.4 to 53.3 +/- 6.9 kg (NS). The mean daily caloric intake of the fed group was significantly increased during the study (p less than 0.02). The mean calorie intake during the study of the fed group was 174 +/- 17% of the estimated basal energy expenditure. During the study period, no change was observed in anthropometric measures, pulmonary function studies, or RMF. Because patients tend to decrease their own food intake while receiving enteral formulas, it is difficult to provide sufficient calories and protein needed to effect changes in nutritional status and RMF in an outpatient COPD population. In addition, we compared RMF in 12 poorly nourished male patients (87.6 +/- 6.1% of ideal body weight) and 13 well-nourished male patients with severe COPD. Both groups had comparable degrees of air-flow limitation and hyperinflation. No difference was noted between the groups in either MIP, MEP, or MSVC.(ABSTRACT TRUNCATED AT 250 WORDS)", "Nutritional depletion commonly occurs in patients with COPD, causing muscle wasting and impaired physiologic function. Two hundred seventeen patients with COPD participated in a placebo-controlled, randomized trial investigating the physiologic effects of nutritional intervention alone (N) for 8 wk or combined with the anabolic steroid nandrolone decanoate (N + A). Nandrolone decanoate or placebo (P) was injected intramuscularly (women, 25 mg; men, 50 mg) in a double-blind fashion on Days 1, 15, 29, and 43. Nutritional intervention consisted of a daily high caloric supplement (420 kcal; 200 ml). Also, all patients participated in an exercise program. In the depleted patients, both treatment regimens induced a similar significant body weight gain (2.6 kg) but different body compositional changes. Particularly in the last 4 wk of treatment, weight gain in the N group was predominantly due to an expansion of fat mass (p < 0.03 versus P and N + A), whereas the relative changes in fat-free mass (FFM) and other measures of muscle mass were more favorable in the N + A group (p < 0.03 versus P). Maximal inspiratory mouth pressure improved within both treatment groups in the first 4 wk of treatment, but after 8 wk only N + A was significantly different from P (p < 0.03). Nutritional supplementation in combination with a short course of anabolic steroids may enhance the gain in FFM and respiratory muscle function in depleted patients with COPD without causing adverse side effects.", "The first aim of this study was to investigate the effects of nutritional supplementation combined with low-intensity exercise on body components, exercise tolerance, and health-related quality of life (HRQOL) in malnourished patients with COPD. The second aim of this study was to examine the degree of systemic inflammation and the actual changes in levels of systemic CRP, TNFα, IL-6 and IL-8 actual changes after a combination of nutritional supplementation and low-intensity exercise in these patients.\n A prospective randomized trial.\n Thirty-two moderate to severe, clinically stable malnourished COPD patients.\n Patients were randomly divided into a nutritional supplementation with low-intensity exercise group and a control group. Lung function, maximum inspiratory and expiratory muscle force, the Chronic Respiratory Disease Questionnaire (CRQ), the 6-min walking distance (6MWD), and the Borg scale were measured at baseline and were re-assessed at 3 months after intervention. The degree of systemic inflammation and the changes in levels of systemic CRP, TNFα, IL-6 and IL-8 were assessed before and after a combination nutritional supplementation with low-intensity exercise.\n Body weight and FFM increased significantly after 12 weeks of nutritional supplementation therapy in patients with COPD. The dietary intake energy increased and the REE:REEpred ratio decreased significantly in the nutrition with low-intensity exercise group. PI(max), Quadriceps muscle force and the 6-min walking distance (6MWD) increased significantly from baseline through week 12. Health status, as assessed by CRQ, improved in the domains of dyspnea and total sores significantly in the nutrition with low-intensity exercise group after intervention. In this group, hsCRP, IL-6, IL-8, and TNFα, decreased significantly after intervention compared with the control group.\n The combination of nutritional supplementation with low-intensity exercise training was successful in increasing weight and energy intake as well as exercise capacity and health-related QOL in our patients. Moreover, REE and major inflammatory cytokines decreased significantly after nutritional supplementation with low-intensity exercise training. The present study results suggest a potential role for the combination of nutritional supplementation and low-intensity exercise in the management of malnourished patients with COPD.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "Pulmonary rehabilitation is effective in improving exercise performance and health status in chronic obstructive pulmonary disease (COPD). However, the role of nutritional support in the enhancement of the benefits of exercise training has not been explored. A double blind, randomised, controlled trial of carbohydrate supplementation was undertaken in patients attending outpatient pulmonary rehabilitation.\n 85 patients with COPD were randomised to receive a 570 kcal carbohydrate rich supplement or a non-nutritive placebo daily for the duration of a 7 week outpatient pulmonary rehabilitation programme. Primary outcome measures were peak and submaximal exercise performance using the shuttle walk tests. Changes in health status, body composition, muscle strength, and dietary macronutrient intake were also measured.\n Patients in both the supplement and placebo groups increased shuttle walking performance and health status significantly. There was no statistically significant difference between treatment groups in these outcomes. Patients receiving placebo lost weight whereas supplemented patients gained weight. In well nourished patients (BMI >19 kg/m(2)) improvement in incremental shuttle performance was significantly greater in the supplemented group (mean difference between groups: 27 (95% CI 1 to 53) m, p<0.05). Increases in incremental shuttle performance correlated with increases in total carbohydrate intake.\n When universally prescribed, carbohydrate supplementation does not enhance the rehabilitation of patients with COPD. This study suggests that exercise training results in negative energy balance that can be overcome by supplementation and that, in selected patients, this may improve the outcome of training. The finding of benefit in well nourished patients may suggest a role for nutritional supplementation beyond the treatment of weight loss in COPD.", "We examined the effect of nutritional supplementation for 13 wk on anthropometric, pulmonary function, and immunological status in malnourished ambulant patients with pulmonary emphysema (EP). The study was placebo controlled, randomized and double blind. Twenty-eight patients were included. Thirteen patients in the fed group were provided with a nutritional formula providing 20% protein, 30% fat, and 50% carbohydrate, 1 Kcal/ml, 400 ml/day. The control group was provided with a reference product of the same consistency and taste containing 0.1 Kcal/ml, 400 ml/day for 13 wk. The fed group had a mean weight gain of 1.5 kg during the study period, the control group increased concomitantly 0.16 kg, the difference being significant (p less than 0.01). Sum of four skinfolds increased 2.7 mm in the fed group, and decreased 0.9 mm in the control group the difference being significant (p less than 0.01). No difference were observed regarding pulmonary function or immunological status. We also found a high habitual energy intake in our study group (204% Basal Energy Expenditure). We conclude that nutritional supplementation produce weight gain in malnourished patients with EP, but it does not change other indices of well-being.", "Malnutrition in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis, yet evidence to support the role of dietary counselling and food fortification is lacking. A study was undertaken to assess the impact of dietary counselling and food fortification on outcome in outpatients with COPD who are at risk of malnutrition.\n A randomised controlled unblinded trial was performed in 59 outpatients with COPD (6 months intervention and 6 months follow-up). The intervention group received dietary counselling and advice on food fortification and the controls received a dietary advice leaflet. Outcome measures were nutritional status, respiratory and skeletal muscle strength, respiratory function, perceived dyspnoea, activities of daily living (ADL) and quality of life.\n The intervention group consumed more energy (difference 194 kcal/day; p = 0.02) and protein (difference 11.8 g/day; p<0.001) than controls. The intervention group gained weight during the intervention period and maintained weight during follow-up; the controls lost weight throughout the study. Significant differences were observed between the groups in St George's Respiratory Questionnaire total score (difference 10.1; p = 0.02), Short Form-36 health change score (difference 19.2; p = 0.029) and Medical Research Council dyspnoea score (difference 1.0; p = 0.03); the difference in ADL score approached statistical significance (difference 1.5; p = 0.06). No differences were observed between groups in respiratory function or skeletal and respiratory muscle strength. Improvements in some variables persisted for 6 months beyond the intervention period.\n Dietary counselling and food fortification resulted in weight gain and improvements in outcome in nutritionally at-risk outpatients with COPD, both during and beyond the intervention period.", "We carried out a prospective randomized controlled trial to investigate the effects of short-term refeeding (16 days) in 10 malnourished inpatients with chronic obstructive pulmonary disease (COPD). Six patients were randomized to receive sufficient nasoenterically administered calories to provide a total caloric intake equal to 1,000 kcal above their usual intake. The other four patients were sham fed, receiving only 100 kcal more. Measurements of nutritional status, respiratory muscle strength and endurance, adductor pollicis function, and pulmonary function were performed initially and at study end. The refed group gained significantly more weight and showed significant increases in maximal expiratory pressure and mean sustained inspiratory pressure. There were no significant changes in the maximal inspiratory pressure or in adductor pollicis function. In malnourished inpatients with COPD, short-term refeeding leads to improvement in respiratory muscle endurance and in some parameters of respiratory muscle strength in the absence of demonstrable changes in peripheral muscle function.", "Limited data are available on effectiveness and costs of nutritional rehabilitation for patients with COPD in community care.\n In a 2-year RCT, 199 COPD patients (FEV(1)%pred. 60% [SD 16%]) and impaired exercise capacity were randomized to the interdisciplinary community-based COPD management program (INTERCOM) or usual care (UC). A prescheduled subgroup analysis was performed on 39 of 199 patients who were muscle wasted and received UC or nutritional therapy in combination with exercise training. Body composition, muscle strength, and exercise capacity were assessed at baseline and 4, 12, and 24 months.\n Between group differences after 4 months in favor of the intervention group: fat free mass index (FFMI 0.9 kg/m(2) [SE = 0.2, P < .001]), body mass index (BMI 1.0 kg/m(2) [SE = 0.4, P = .009]), maximum inspiratory mouth pressure (Pimax 1.4 kPa [SE = 0.5, P = .011]), quadriceps average power (QAP 13.1 Watt [SE=5.8, P = .036]), 6-minute walking distance (6MWD 27 m, [SE = 11.5, P = .028]), cycle endurance time (CET 525 seconds [SE=195, P = .013]), and peak exercise capacity (Wmax 12 Watt [SE = 5, P = .036]). Between group difference over 24 months in favor of the intervention group: Pimax 1.7 kPa (SE = 0.53, P = .004), QAP 19 Watt (SE = 6, P = .005), 6MWD 57 (SE = 19, P = .006), and CET 485 seconds (SE = 159, P = .006). After 4 months total costs were Euro 1501 higher in the intervention group than in the UC group (P < .05), but not significantly different after 24 months. Hospital admission costs were significantly lower in the intervention group -euro 4724 (95% CI -7704, -1734).\n This study in muscle-wasted COPD patients with moderate airflow obstruction shows a prolonged positive response to nutritional support integrated in a community-based rehabilitation program.\n (c) 2010 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.", "The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population.", "Patients with chronic obstructive pulmonary disease (COPD) often suffer from weight loss. The aim of the present study was to gain insight into the energy balance of depleted ambulatory COPD patients, in relation to their habitual level of physical activity and consumption of oral nutritional supplements. Clinically stable and weight-stable patients (n 20; BMI 19.8+/- SD 2.0 kg/m2) were studied 1 and 3 months after rehabilitation or recovery in the clinic and were at random assigned to a control or intervention group with regard to nutritional supplementation. Energy intake was measured with a 7 d food record. Energy expenditure was estimated from a simultaneous 7 d assessment of physical activity with a tri-axial accelerometer for movement registration in combination with measured BMR. Body mass was measured at several time points. The body mass remained stable in both groups after 1 or 3 months and mean energy balances were comparable for both groups. The mean body-mass change between month 1 and 3 was negatively related to the mean physical activity level (r -0.49; P=0.03). Weight change over the 3 months was negatively associated with the physical activity level. These results suggest that knowledge about the individual physical activity level is necessary for the estimation of the energy need of the COPD patient.", "Nine patients with advanced chronic obstructive pulmonary disease (COPD) and recent weight loss resulting in a state of mild malnutrition were entered into a refeeding program at a clinical research center. They were divided into two groups, one using a hospital diet and the other a hospital diet with supplementation. Both groups of patients gained significant weight. Refeeding and weight gain were associated with a significant increase in absolute lymphocyte count and with an increase in reactivity to skin test antigens after 21 days of refeeding. Few changes occurred in large numbers of additional serum measurements during the study period. These preliminary observations suggest that dietary and supplementary refeeding may improve the immune responses in patients with COPD.", "One of the major pathophysiologies in advanced chronic obstructive pulmonary disease (COPD) has been attributed to systemic inflammation. Meta-analysis of the 2005 Cochrane Database concluded the effect of nutritional supplementation alone on stable COPD was insufficient to promote body weight gain or exercise capacity. The aim of this study was to investigate the effectiveness of nutritional supplementation therapy using a nutritional supplement containing whey peptide with low-intensity exercise therapy in stable elderly patients with COPD.\n In stable elderly COPD patients with %IBW and %FEV(1) of less than 110 and 80%, respectively, anti-inflammatory nutritional supplementation therapy was added to low-intensity exercise therapy. Thirty-six COPD patients were divided into those with and those without the ingestion of an anti-inflammatory nutritional supplement containing whey peptide, which exhibited an anti-inflammatory effect. These two groups were designated as the nutritional support and the control groups, respectively. The body composition, skeletal muscle strength, exercise tolerance, health-related QOL (HRQOL), and inflammatory cytokines were evaluated before and three months after nutritional support combined with exercise therapy in both the nutritional support group and the control group.\n In the nutritional support group, the body weight, %IBW, FM, energy intake, %AC, Alb, PImax, PEmax, 6MWD, WBI, emotional function, and CRQ total were significantly increased, and the levels of hsCRP, IL-6, IL-8, and TNF-α were reduced significantly, while no significant change was noted in any item of physiological evaluation or any biomarker in the control group.\n Concomitant use of a anti-inflammatory nutritional supplement containing whey peptide, which exhibits an anti-inflammatory effect, with exercise therapy in stable elderly COPD patients with %IBW<110% and %FEV(1)<80% may not only increase body weight but may also inhibit systemic inflammation and thus improve exercise tolerance and HRQOL.\n Copyright © 2012 Elsevier Ltd. All rights reserved." ]

[ "6600826", "6611576" ]

[ "Transcutaneous electrical nerve stimulation in rheumatoid arthritis.", "The analgesic effects of transcutaneous electrical nerve stimulation and placebo in chronic pain patients. A double-blind non-crossover comparison." ]

[ "The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a randomised, double-blind, non-crossover study lasting three weeks. Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated. Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping. In addition, grip strength, measured as power and work done, immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessments. No significant improvement was shown for the placebo group.", "The analgesic effects of high frequency transcutaneous electrical nerve stimulation (TNS), \"acupuncture-like\" TNS and placebo TNS were evaluated in 33 patients with rheumatoid arthritis and chronic hand pain using a randomized, double-blind, non-crossover design. An oscilloscope was employed to monitor the stimulator output in the TNS treatment groups and to provide strong suggestion and a focus of attention in the placebo treatment group. The two forms of TNS were applied at the highest intensity that could be tolerated by patients. Assessments of resting pain, joint tenderness, grip strength and grip pain were made before and after treatment. The pain and joint tenderness measurements showed high frequency TNS, \"acupuncture-like\" TNS and placebo TNS to be equally effective in producing analgesia of similar degree and trend over time. The grip strength measurements showed no significant change. The results obtained with placebo are probably due to the suggestion and attention effects of the visual stimulus. The implications of these results in respect to pain control pathways are discussed. Although TNS given at high intensity was shown to be no better than placebo applied with strong suggestion, this does not preclude its use as a method of pain control in rheumatoid arthritis." ]

[ "15265052", "8455970", "9529766", "12421159", "3885921", "7775175", "7007285" ]

[ "A randomized, double blind study of the prophylactic effect of hyperbaric oxygen therapy on migraine.", "Hyperbaric oxygen therapy in cluster headache.", "Hyperbaric oxygen in the treatment of migraine with aura.", "Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study.", "Treatment of cluster headache. A double-blind comparison of oxygen v air inhalation.", "A preliminary report on hyperbaric oxygen in the relief of migraine headache.", "Response of cluster headache attacks to oxygen inhalation." ]

[ "In a double blind, placebo-controlled study to assess the prophylactic effect of hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a treatment group receiving three sessions of hyperbaric oxygen, or a control group receiving three hyperbaric air treatments. The patients were instructed to keep a standardized migraine diary for eight weeks before and after the treatment. Thirty-four patients completed the study. Our primary measure of efficacy was the difference between pre- and post-treatment hours of headache per week. The results show a nonsignificant reduction in hours of headache for the hyperbaric oxygen group compared to the control group. Levels of endothelin-1 in venous blood before and after treatment did not reveal any difference between the hyperbaric oxygen and control groups. We conclude that the tested protocol does not show a significant prophylactic effect on migraine and does not influence the level of endothelin-1 in venous blood.", "Preliminary reports have shown that hyperbaric oxygen (HBO) interrupts cluster headache (CH) attacks. In the present study, 6 of 7 patients with episodic cluster headache who were treated with hyperbaric oxygen experienced an interruption of the attack. In 3 of 6 responders the florid period of the cluster headache was interrupted. The other 3 patients remained without pain attacks for a period lasting from 3 to 6 days. In 6 different patients, a placebo treatment had no effect. The present findings clearly indicate that hyperbaric oxygen has not only a symptomatic effect on a single attack of cluster headache, but it also could prevent the occurrence of subsequent attacks.", "Cephalalgia is one of the most common medical complaints and the search continues for relief. Early treatments for migraine included inhalation of 100% oxygen. It has been theorized that the increased levels of oxygen in the blood act as an alpha-adrenergic agent to alleviate headache pain through vasoconstriction and local metabolic effects. The presence of muscle tenderness during some migraine headaches has also been established. The purpose of this study was to document relief of cephalalgia through use of a visual analog pain scale, algometry, and manual palpation. Female subjects with confirmed migraine were randomly assigned to begin with either the control (100% oxygen, no pressure) or hyperbaric treatment (100% oxygen, pressure). Manual palpation and algometry of 10 sites were done, bilaterally, by a trained specialist. Pain was evaluated with a visual analog scale. Resolution of tenderness and edema following both treatments was observable by manual palpation while algometry showed no differences between the two. Subjective pain was significantly decreased following hyperbaric oxygen treatment but not following the control treatment. Results suggest that hyperbaric oxygen treatment reduces migraine headache pain and that the patient's subjective assessment was the best indicator of relief.", "Sixteen patients, 12 with episodic and four with chronic cluster headache (CH) according to the International Headache Society criteria (1), participated in the study. They were randomly selected to start with one out of two different hyperbaric treatments in a double-blind, placebo-controlled, cross-over study design. Both gases were administered by mask inside a multiplace hyperbaric chamber for 70 min at 250 kPa (2.5 ATA) in two sessions 24 h apart. Active treatment was 100% oxygen (HBO treatment), while placebo treatment was 10% oxygen in nitrogen (hyperbaric normoxic placebo = sham treatment) corresponding to breathing air at sea level. All patients were decompressed on air. The patients documented the number of headache attacks and their degree of severity according to a modified VAS scale (level 0-4, where level 0 = no headache and level 4 = very severe headache). A headache index (HI = sum of (number of attacks times degree of severity)) was calculated for the run-in week prior to and the week after each separate treatment. A treatment was regarded as effective if it reduced the HI by>50%. Blood samples were taken from the external jugular vein before and during hyperbaric treatment (after 30 and 70 min), 1 day and 1 week after each treatment for analyses of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) and in a few patients also endotheline and nitrate. No difference between HBO and sham treatment on the HI or the prophylactic effect was observed in our study. However, 83% of the episodic CH patients and 25% of the chronic ones responded to either of the two treatments with at least 50% reduction of HI or remission for shorter or longer periods. This response rate exceeds an expected high placebo response due to the study procedure. Two episodic CH patients still experienced remission on follow-up 1 year after sham treatment. Five patients reported mild or moderate CH attacks during the sham treatment, and none during the HBO treatment. Changes in neuropeptides, endotheline and nitrate levels did not differ systematically when comparing the two different hyperbaric treatments or with respect to responders and non-responders. We conclude that two HBO sessions were not more effective than two sham treatments in reducing the HI and interrupting the CH period when given in a well-established cluster period or in chronic CH. The hyperbaric condition itself seems effective in reducing the HI, at least in patients with episodic CH, although a powerful placebo response can not be ruled out.", "Nineteen men, aged 20 to 50 years, were treated in a double-blind crossover study comparing oxygen v air inhalation at 6 L/min via nonrebreathing face masks for 15 minutes or less, for up to six headaches. Patients scored their own degree of relief for each treatment as none, slight, substantial, or complete relief. The average (+/- SE) relief score for all oxygen-treated patients was 1.93 +/- 0.22 out of a possible total score of 3.0, and for air the treatment relief score was 0.77 +/- 0.23. This difference is highly statistically significant by an analysis-of-variance F test; it documents that patients with cluster headache can benefit from oxygen inhalation during acute attacks.", "Oxygen inhalation was early advocated as a treatment for migraine headache. It has been theorized that the efficacy of raising blood oxygen levels in vascular headache is mediated by vasoconstriction and metabolic effects. Hyperbaric oxygen can provide a much greater level of blood oxygenation than can provide a much greater level of blood oxygenation than normobaric oxygen, and in recent studies it has been used in the treatment of cluster headache. The purpose of this study was to compare the effects of hyperbaric oxygen and normobaric oxygen in migraine. Twenty migraineurs were divided randomly into two groups and studied in a hyperbaric chamber during a typical headache attack. Global headache severity was measured by a verbal descriptor scale before and after exposure to oxygen. One group received 100% oxygen at 1 atmosphere of pressure (normobaric) while the other received 100% oxygen at 2 atmospheres of pressure (hyperbaric). One of the 10 patients in the normobaric group achieved significant relief of headache symptoms, while 9 of 10 in the hyperbaric group found relief. Based on a chi-square test, this difference is significant at the P < .005 level. Those patients who did not find significant relief from normobaric oxygen were given hyperbaric oxygen as above. All nine found significant relief. The results suggest that hyperbaric (but not normobaric) oxygen may be useful in the abortive management of migraine headache. Possibilities for the mechanism of this effect, in addition to vasoconstriction, include an increase in the rate of energy-producing and neurotransmitter-related metabolic reactions in the brain which require molecular oxygen.", "nan" ]

[ "12641399", "7036765", "14728606", "3048759", "12504399", "11502317", "2286005", "9692160", "3293827", "12163917", "12363058", "12535245" ]

[ "Comparative efficacy of aminoquinoline-antifolate combinations for the treatment of uncomplicated falciparum malaria in Kampala, Uganda.", "Sulfadoxine-pyrimethamine for the treatment of acute malaria in children of Papua New Guinea. II. Plasmodium vivax.", "The efficacy of chloroquine, sulfadoxine-pyrimethamine and a combination of both for the treatment of uncomplicated Plasmodium falciparum malaria in an area of low transmission in western Uganda.", "Effectiveness of amodiaquine, sulfadoxine-pyrimethamine, and combinations of these drugs for treating chloroquine-resistant falciparum malaria in Hainan Island, China.", "Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial.", "Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial.", "[Comparative study of sulfadoxine-pyrimethamine and amodiaquine + sulfadoxine-pyrimethamine for the treatment of malaria caused by chloroquine-resistant Plasmodium falciparum in Maputo, Mozambique].", "A trial of Fansidar plus chloroquine or Fansidar alone for the treatment of uncomplicated malaria in Gambian children.", "Evaluation of four therapeutic regimens for falciparum malaria in Mozambique, 1986.", "Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamine-amodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.", "The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.", "Therapeutic efficacy of chloroquine plus sulphadoxine/ pyrimethamine compared with monotherapy with either chloroquine or sulphadoxine/pyrimethamine in uncomplicated Plasmodium falciparum malaria in Laos." ]

[ "Resistance to chloroquine (CQ) requires its replacement as first-line therapy for uncomplicated malaria in much of Africa. Combination therapy may improve efficacy and delay the selection of resistant malaria parasites. Combinations of sulfadoxine-pyrimethamine (SP) with 4-aminoquinolines offer affordable and available alternatives to CQ. We conducted a randomized, single-blinded trial to compare the efficacy of SP monotherapy with combinations of SP and either CQ or amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria in patients over 6 months of age in Kampala, Uganda. Of the 448 patients enrolled, 428 (95%) completed follow-up. Clinical treatment failure after 14 days occurred in 21/140 (15.0%, 95% CI 9.5-22.0%) SP-treated, 11/152 (7.2%, 95% CI 3.7-12.6%) SP/CQ-treated, and 0/136 (0%, 95% CI 0-2.7%) SP/AQ-treated patients. Combination therapies were safe and offered superior efficacy to SP monotherapy. SP/AQ was the most efficacious. This low-cost combination regimen may provide an optimal alternative to CQ for the treatment of uncomplicated malaria in Uganda.", "In Papua New Guinea, Plasmodium falciparum and P. vivax are common causes of acute malaria in children and P. malariae an uncommon cause. The increasing prevelance of chloroquine-resistant strains of P. falciparum in Papua New Guinea has prompted the search for alternatives to chloroquine as standard presumptive treatment. Sulfadoxine-pyrimethamine, either alone or in combination with a single dose of chloroquine, was compared with chloroquine alone for treatment of acute vivax malaria in children in Madang. Fever resolution was slowest in the group treated with sulfadoxine-pyrimethamine alone, and time to clearance of parasitemia was significantly longer in this group (P less than 0.001). Where possible, species identification should be undertaken in acute malaria and cases of P. vivax treated with chloroquine.", "We conducted an efficacy study of chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and a combination of both (SP+CQ) for the treatment of uncomplicated malaria in an area of low transmission with low drug pressure. On day 3, fever clearance was 97.4% (95% CI, 86.8-99.9), 100% (95% CI, 87.2-100) and 96.6% (95% CI, 82.2-99.9) in the CQ, SP and SP+CQ groups, respectively, (P=0.65). On day 14, clinical success was 92.5% (95% CI, 79.6-98.4), 100% (95% CI, 87.2-100) and 100% (95% CI, 88.1-100) in the CQ, SP and CQ+SP groups, respectively. Clinical failure was seen in 7.5% with 5% (95% CI, 0.61-16.9) early treatment failure and 2.5% (95% CI, 0.06-13.2) late treatment failure of cases in the CQ group and 0% in the SP and SP+CQ groups. Parasitological resistance was observed at RI level in 10% (95% CI, 2.8-23.7), 18.5% (95% CI, 6.3-38.1) and 6.9% (95% CI, 0.85-22.8) for the CQ, SP and SP+CQ, respectively (P=0.37). There was no age-dependent difference in clinical failure or parasitological resistance in any of the treatment groups and prior CQ use within the last 2 weeks did not affect CQ treatment outcome. The findings of this study suggest that CQ is still effective for the treatment of uncomplicated malaria in this area of low transmission and SP. However, combination therapy of SP+CQ is recommended to delay the development SP resistance, and regular surveillance for emerging CQ and SP resistance is needed to plan for alternative antimalarial drug regimens.", "The study was carried out in 1985-86 in Hainan Island where Plasmodium falciparum is resistant to chloroquine. Fifty cases of falciparum malaria were treated with 1800 mg amodiaquine for 3 days: the cure rate was 65.3%, and the mean time to clear fever and asexual parasitaemia was 30.7 and 60.3 hours, respectively; 34.7% of cases showed RI or RII recrudescence, and one patient's temperature did not come down to normal within 7 days.Twenty-one cases were treated with sulfadoxine-pyrimethamine (1500 mg and 75 mg, respectively): 19 were cured, I showed RI and another had an S or RI response; the mean time for fever control was 56.1 hours.Fifty cases were treated with amodiaquine plus sulfadoxine and 49 received amodiaquine plus sulfadoxine-pyrimethamine: the cure rate was 97.9% and 100%, respectively; the mean time for fever clearance was 25.0 and 25.7 hours and for parasite clearance 57.1 and 52.8 hours, respectively. These drug combinations gave much better results for cure and for symptom control than amodiaquine or sulfadoxine-pyrimethamine alone, and may be considered for treatment of chloroquine-resistant falciparum malaria.", "New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda.\n We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol.\n 183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate.\n Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.", "Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance.\n Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed.\n 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041).\n Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.", "To compare the efficacy and side-effects of two therapeutic regimens for chloroquine-resistant falciparum malaria, a randomized study was carried out in 69 patients in Maputo Central Hospital in 1986-1987. The two treatments were sulfadoxine 25 mg/kg + pyrimethamine 1.25 mg/kg as a single dose (S + P) and amodiaquine 10 + 10 + 5 mg/kg over three days with sulfadoxine + pyrimethamine on the third day (A + S + P). The cure rate was 25/29 (86%) with S + P and 27/30 (90%) with A + S + P. No serious side-effects were observed. The probably slightly higher cure rate with the triple combination is hardly of clinical importance in semi-immune patients, but may theoretically help retard the development of resistance to sulfadoxine-pyrimethamine. This point and the question of the incidence of side-effects with the two regimens should be made the object of an epidemiological study.", "Chloroquine can no longer be recommended as the first-line treatment for uncomplicated malaria in several parts of Africa because of the increasing prevalence of chloroquine resistance. However, chloroquine was a highly effective treatment for malaria not only because of its ability to kill parasites quickly but also because it is an anti-inflammatory drug. Therefore, we have investigated whether Fansidar (pyrimethamine/sulfadoxine) plus chloroquine is a more effective treatment for uncomplicated malaria than Fansidar alone. Four hundred and five Gambian children with uncomplicated Plasmodium falciparum malaria were studied in a randomized controlled trial. Significantly more children treated with Fansidar alone, compared to those treated with Fansidar plus chloroquine (19/203 vs. 2/202; P < 0.001), returned to the clinic with persistent symptoms during the first 3 d after treatment. Three children who had received Fansidar alone had fits, but none of the children treated with Fansidar plus chloroquine did so. At the day 7 follow-up, the parasite failure rate in the Fansidar alone group was 3/198 (1.5%), whilst in the Fansidar plus chloroquine group it was 3/201 (1.5%). At the day 28 follow-up, there was still no significant difference between the parasite failure rate in the Fansidar alone group (15/150; 10.0%) and the Fansidar plus chloroquine group (7/141; 5.0%) and the mean packed cell volume (PCV) in the 2 groups was similar. Thus, a combination of Fansidar plus chloroquine was a more effective symptomatic treatment than Fansidar given alone, but neither the parasite cure rate nor the PCV was enhanced by use of the combination.", "A randomized study on the effect of the following four treatment regimens on Plasmodium falciparum parasitaemia was carried out on 200 asymptomatic schoolchildren in Maputo, Mozambique: chloroquine (25 mg/kg body weight), amodiaquine (25 mg/kg), sulfadoxine-pyrimethamine (25 mg/kg and 1.25 mg/kg), or amodiaquine (25 mg/kg) + sulfadoxine-pyrimethamine (25 mg/kg and 1.25 mg/kg) administered on the third day of the study. The results of in vivo tests indicated that 94% of the infections were resistant to chloroquine, 76% to amodiaquine, and 16% to sulfadoxine-pyrimethamine. The cure rate with amodiaquine + sulfadoxine-pyrimethamine was 100%, which was not significantly different from that with sulfadoxine-pyrimethamine alone; the latter regimen was the most rapidly acting of the treatments studied. It is concluded that amodiaquine is not an appropriate substitute for chloroquine, but that the effect of the combination amodiaquine + sulfadoxine-pyrimethamine may be superior to that of sulfadoxine-pyrimethamine alone, although this requires further study.", "To evaluate the therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine, and the sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon.\n In a randomized study we evaluated the effectiveness and tolerance of (i) sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs.\n Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects.\n SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited.", "The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P = 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P = 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.", "In a southern border province of Lao PDR, we compared the efficacy of antimalarial drug combinations in patients aged >or=1 year with uncomplicated Plasmodium falciparum malaria: monotherapy with either mefloquine (MQ), chloroquine (CQ), or sulphadoxine/pyrimethamine (SP) vs. the combination of both CQ and SP. Follow-up time was 14 days. Of 265 P. falciparum positive patients, 119 were enrolled in the drug trial. Significantly more patients treated with CQ than with SP developed early or late treatment failure [44.8%vs. 17.9%, relative risk (RR) = 2.51, 95% CI 1.03-6.12]. In the SP group, 82.1% were sensitive and 17.9% were treatment failures. The combination treatment CQ plus SP resulted in 83.3% sensitivity and 16.7% treatment failures. Combination treatment has no advantage over monotherapy with SP (RR = 1.01, 95% CI 0.8-1.3). All patients who received MQ for treatment (total dose 25 mg/kg) were cured within the 14 days of follow-up. The findings of this study suggest that use of CQ as first-line treatment of uncomplicated malaria in the Lao PDR has to be reconsidered. The combination of both CQ and SP has been discussed as a cost-effective alternative treatment, but in our patient population achieved no better results than single therapy with SP." ]

[ "8853248", "10486353", "15729231", "15138203", "11034574", "16185958", "17405999", "19474425", "16905695", "18043104", "12616111", "15606390", "16118910" ]

[ "Failure of Nd-YAG photocoagulation therapy as treatment for Barrett's oesophagus--a pilot study.", "Endoscopic regression of Barrett's oesophagus during omeprazole treatment; a randomised double blind study.", "Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus.", "5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett's oesophagus: a randomised trial.", "Photodynamic therapy for dysplastic Barrett's oesophagus: a prospective, double blind, randomised, placebo controlled trial.", "Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial.", "Secondary chemoprevention of Barrett's esophagus with celecoxib: results of a randomized trial.", "Radiofrequency ablation in Barrett's esophagus with dysplasia.", "A randomised controlled trial of ablation of Barrett's oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results.", "Randomized trial of argon plasma coagulation versus endoscopic surveillance for barrett esophagus after antireflux surgery: late results.", "Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus.", "Endoscopic ablation of Barrett's oesophagus: a randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation.", "Endoscopic ablation of dysplastic Barrett's oesophagus comparing argon plasma coagulation and photodynamic therapy: a randomized prospective trial assessing efficacy and cost-effectiveness." ]

[ "Acid suppression therapy and surgical antireflux procedures have not consistently led to regression of Barrett's epithelium. We reasoned that laser photocoagulation in combination with powerful acid suppression might destroy the metaplastic columnar epithelium and allow the area to be replaced by normal squamous mucosa.\n Eight patients with endoscopic and histologically proven Barrett's oesophagus were recruited into the study. Four patients were randomized to receive omeprazole 40 mg daily and four patients received the same medical therapy plus repeated laser photocoagulation administered at 4-6 weekly intervals. Endoscopies were performed on entry and at 6 months. The extent of Barrett's epithelium was assessed and mapped on to a grid system and histological changes were assessed in blinded manner by a single histopathologist. One new quadrant of Barrett's segment was irradiated per treatment.\n Laser therapy was well tolerated and no complications occurred. After 6 months, the extent of Barrett's epithelium was unchanged in both groups. There was no appearance of squamous islands either endoscopically or microscopically in areas treated with laser.\n Nd-YAG laser is ineffective in ablating Barrett's epithelium.", "Barrett's oesophagus, columnar metaplasia of the epithelium, is a premalignant condition with a 50-100-fold increased risk of cancer. The condition is caused by chronic gastro-oesophageal reflux. Regression of metaplasia may decrease the cancer risk.\n To determine whether elimination of acid gastro-oesophageal reflux induces a regression of metaplastic epithelium.\n Sixty eight patients with acid reflux and proven Barrett's oesophagus were included in a prospective, randomised, double blind study with parallel groups, and were treated with profound acid secretion suppression with omeprazole 40 mg twice daily, or with mild acid secretion suppression with ranitidine 150 mg twice daily, for 24 months. Endoscopy was performed at 0, 3, 9, 15, and 24 months with measurement of length and surface area of Barrett's oesophagus; pH-metry was performed at 0 and 3 months. Per protocol analysis was performed on 26 patients treated with omeprazole, and 27 patients treated with ranitidine.\n Omeprazole reduced reflux to 0.1%, ranitidine to 9.4% per 24 hours. Symptoms were ameliorated in both groups. There was a small, but statistically significant regression of Barrett's oesophagus in the omeprazole group, both in length and in area. No change was observed in the ranitidine group. The difference between the regression in the omeprazole and ranitidine group was statistically significant for the area of Barrett's oesophagus (p=0. 02), and showed a trend in the same direction for the length of Barrett's oesophagus (p=0.06).\n Profound suppression of acid secretion, leading to elimination of acid reflux, induces partial regression of Barrett's oesophagus.", "Endoscopic ablation of Barrett's esophagus has been described in which various thermocoagulation modalities are used in combination with a high dose of a proton pump inhibitor. No randomized comparison of ablation strategies has been published.\n Referred patients were screened to identify those with Barrett's esophagus 2 to 7 cm in length, without high-grade dysplasia or cancer. Included patients received pantoprazole (40 mg twice a day), followed by randomization to treatment with argon plasma coagulation (APC) or multipolar electrocoagulation (MPEC). The primary outcome measure was the number of treatment sessions required for endoscopic ablation.\n Of 235 patients screened, 52 were randomized. The mean length of Barrett's esophagus was 3.1 cm in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the treatment groups were similar with regard to baseline characteristics. The mean number of treatment sessions required for endoscopic ablation was 2.9 for MPEC vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after adjustment for the difference in length of Barrett's esophagus). The proportion of patients in which ablation was endoscopically achieved proximal to the gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21). The mean time required for the first treatment session was 6 minutes with MPEC vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious adverse event, but transient moderate to severe upper-GI symptoms occurred after MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no statistically significant differences, ablation of Barrett's esophagus with pantoprazole and MPEC required numerically fewer treatment sessions, and endoscopic and histologic ablation was achieved in a greater proportion of patients compared with treatment with pantoprazole and APC.", "Photochemical and thermal methods are used for ablating Barrett's oesophagus (BO). The aim of this study was to compare 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) with argon plasma coagulation (APC) with respect to complete reversal of BO.\n Patients with BO (32 no dysplasia and eight low grade dysplasia) were randomised to one of three treatments: (a) ALA-PDT as a single dose of 100 J/cm(2) at four hours (PDT100; n = 13); (b) ALA-PDT as a fractionated dose of 20 and 100 J/cm(2) at one and four hours, respectively (PDT20+100; n = 13); or (c) APC at a power setting of 65 W in two sessions (APC; n = 14). If complete elimination of BO was not achieved by the designated treatment, the remaining BO was treated by a maximum of two sessions of APC.\n Mean endoscopic reduction of BO at six weeks was 51% (range 20-100%) in the PDT100 group, 86% (range 0-100%) in the PDT20+100 group, and 93% (range 40-100%) in the APC group (PDT100 v PDT20+100, p<0.005; PDT100 v APC, p<0.005; and PDT20+100 v APC, NS) with histologically complete ablation in 1/13 (8%) patients in the PDT100 group, 4/12 (33%) in the PDT20+100 group, and 5/14 (36%) in the APC group (NS). Remaining BO was additionally treated with APC in 23/40 (58%) patients. Histological examination at 12 months revealed complete ablation in 9/11 (82%) patients in the PDT100 group, in 9/10 (90%) patients in the PDT20+100 group, and in 8/12 (67%) patients in the APC group (NS). At 12 months, no dysplasia was detected. Side effects (that is, pain (p<0.01), and nausea and vomiting (p<0.05)) and elevated liver transaminases (p<0.01) were more common after PDT than APC therapy. One patient died three days after treatment with PDT, presumably from cardiac arrhythmia.\n APC alone or ALA-PDT in combination with APC can lead to complete reversal of Barrett's epithelium in at least two thirds of patients when administered in multiple treatment sessions. As the goal of treatment should be complete reversal of Barrett's epithelium, we do not recommend these techniques for the prophylactic ablation of BO.", "Photodynamic therapy (PDT) is a treatment in which cell damage is achieved by the action of light on a photosensitizing agent. We have assessed the potential use of PDT in the ablation of Barrett's oesophagus.\n Thirty six patients with dysplastic Barrett's oesophagus receiving acid suppression medication with omeprazole were randomised to receive oral 5-aminolaevulinic acid (ALA) 30 mg/kg or placebo, followed four hours later by laser endoscopy. Follow up endoscopy was performed at one, six, 12, and 24 months.\n Of 18 patients in the ALA group, a response was seen in 16 (median decrease in area in the treated region 30%; range 0-60%). In the placebo group, a decrease in area of 10% was observed in two patients with no change in 16 (median 0%; range 0-10%; treatment v placebo, p<0.001). No dysplasia was seen in the columnar epithelium within the treatment area of any patient in the PDT group. However, in the placebo group, persistent low grade dysplasia was found in 12 patients (p<0.001). There were no short or long term major side effects. The effects of treatment were maintained for up to 24 months.\n This is the first randomised controlled trial of PDT for Barrett's oesophagus. It demonstrates that ALA induced PDT can provide safe and effective ablation of low grade dysplastic epithelium.", "Barrett's esophagus (BE) may lead to high-grade dysplasia (HGD) and adenocarcinoma. The objective was to examine the impact of treating patients with BE and with HGD by using porfimer sodium (POR) and photodynamic therapy (PDT) for ablating HGD and reducing the incidence of esophageal adenocarcinoma.\n The design was a multicenter, partially blinded (pathology), randomized clinical trial conducted in patients with BE who have HGD. There were 30 contributing centers. A total of 485 patients were screened, with 208 in the intent-to-treat population and 202 in the safety population. Patients were randomized on a 2:1 basis to compare PDT with POR plus omeprazole (PORPDT) with omeprazole only (OM). The main outcome measurement was complete HGD ablation occurring at any time during the study period.\n There was a significant difference (p < 0.0001) in favor of PORPDT (106/138 [77%]) compared with OM (27/70 [39%]) in complete ablation of HGD at any time during the study period. The occurrence of adenocarcinoma in the PORPDT group (13%) (n=18) was significantly lower (p < 0.006) compared with the OM group (28%) [corrected] (n=20). The safety profile showed 94% of patients in the PORPDT group and 13% of patients in the OM group had treatment-related adverse effects. The limitations of the study were that PDT therapy may have had to be applied more than once and that patients spent more time in treatment. The patients and the physicians were not blinded to the treatment.\n PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma.", "Barrett's esophagus is a premalignant condition that is a risk factor for the development of esophageal adenocarcinoma, a disease whose incidence is rapidly increasing. Because aspirin and other nonsteroidal anti-inflammatory drugs, such as celecoxib, may decrease the risk of developing esophageal cancer, we investigated the effect of long-term administration of celecoxib in patients with Barrett's esophagus with dysplasia.\n Chemoprevention for Barrett's Esophagus Trial (CBET) is a phase IIb multicenter randomized placebo-controlled trial of celecoxib in patients with Barrett's esophagus and low- or high-grade dysplasia. Patients were randomly assigned to treatment with 200 mg of celecoxib or placebo, both administered orally twice daily, and then stratified by grade of dysplasia. The primary outcome was the change from baseline to 48 weeks of treatment in the proportion of biopsy samples with dysplasia between the celecoxib and placebo arms. Secondary and tertiary outcomes included evaluation of changes in histology and expression levels of relevant biomarkers. All statistical tests were two-sided.\n From April 1, 2000, through June 30, 2003, 222 patients were registered into CBET, and 100 of them with low- or high-grade Barrett's dysplasia were randomly assigned to treatment (49 to celecoxib and 51 to placebo). After 48 weeks of treatment, no difference was observed in the median change in the proportion of biopsy samples with dysplasia or cancer between treatment groups in either the low-grade (median change with celecoxib = -0.09, interquartile range [IQR] = -0.32 to 0.14 and with placebo = -0.07, IQR = -0.26 to 0.12; P = .64) or high-grade (median change with celecoxib = 0.12, IQR = -0.31 to 0.55, and with placebo = 0.02, IQR = -0.24 to 0.28; P = .88) stratum. No statistically significant differences in total surface area of the Barrett's esophagus; in prostaglandin levels; in cyclooxygenase-1/2 mRNA levels; or in methylation of tumor suppressor genes p16, adenomatous polyposis coli, and E-cadherin were found with celecoxib compared with placebo.\n Administration of 200 mg of celecoxib twice daily for 48 weeks of treatment does not appear to prevent progression of Barrett's dysplasia to cancer.", "Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression.\n In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barrett's esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia.\n In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture.\n In patients with dysplastic Barrett's esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)\n 2009 Massachusetts Medical Society", "Many modalities have been used to ablate Barrett's oesophagus (BO). However, long term results and comparative effectiveness are unknown.\n Our aim was to compare the long term efficacy of achieving complete reversal (endoscopic and histological) between multipolar electrocoagulation (MPEC) and argon plasma coagulation (APC) in BO patients and assess factors influencing successful ablation.\n Patients with BO, 2-6 cm long, underwent 24 hour pH testing on proton pump inhibitor (PPI) therapy. Patients were then randomised by BO length to undergo ablation with MPEC or APC every 4-8 weeks until endoscopic reversal or maximal of six treatment sessions.\n Thirty five BO patients have been followed for at least two years following endoscopic ablation, 16 treated with MPEC and 19 with APC. There was complete reversal of BO in 24 patients (69%); 75% with MPEC and 63% with APC (p = 0.49). There was no difference in the number of sessions required in the two groups. There was no difference in age, pH results, BO length, PPI dose, or hiatal hernia size between patients with and without complete reversal. One patient developed an oesophageal stricture but there were no major complications such as bleeding or perforation.\n In BO patients treated with MPEC or APC in combination with acid suppression, at long term follow up, complete reversal of BO can be maintained in approximately 70% of patients, irrespective of the technique. There are no predictors associated with achieving complete reversal of BO. Continued surveillance is still indicated in the post ablative setting. As yet, these techniques are not ready for clinical application (other than for high grade dysplasia or early oesophageal adenocarcinoma) and cannot be offered outside the research arena.", "To determine the efficacy of endoscopic argon plasma coagulation (APC) for ablation of Barrett esophagus.\n APC has been used to ablate Barrett esophagus. However, the long-term outcome of this treatment is unknown. This study reports 5-year results from a randomized trial of APC versus surveillance for Barrett esophagus in patients who had undergone a fundoplication for the treatment of gastroesophageal reflux.\n Fifty-eight patients with Barrett esophagus were randomized to undergo either ablation using APC or ongoing surveillance. At a mean 68 months after treatment, 40 patients underwent endoscopy follow-up. The efficacy of treatment, durability of the neosquamous re-epithelialization, and safety of the procedure were determined.\n Initially, at least 95% ablation of the metaplastic mucosa was achieved in all treated patients. At the 5-year follow-up, 14 of 20 APC patients continued to have at least 95% of their previous Barrett esophagus replaced by neosquamous mucosa, and 8 of these had complete microscopic regression of the Barrett esophagus. Five of the 20 surveillance patients had more than 95% regression of their Barrett esophagus, and 4 of these had complete microscopic regression (1 after subsequent APC treatment). The length of Barrett esophagus shortened significantly in both study groups, although the extent of regression was greater after APC treatment (mean 5.9-0.8 cm vs. 4.6-2.2 cm). Two patients who had undergone APC treatment developed a late esophageal stricture, which required endoscopic dilation, and 2 patients in the surveillance group developed high-grade dysplasia during follow-up.\n Regression of Barrett esophagus after fundoplication is more likely, and greater in extent, in patients who undergo ablation with APC. In most patients treated with APC the neosquamous mucosa remains stable at up to 5-year follow-up. The development of high-grade dysplasia only occurred in patients who were not treated with APC.", "To compare the results of medical treatment and antireflux surgery in patients with Barrett's esophagus (BE).\n The treatment of choice in BE is still controversial. Some clinical studies suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and adenocarcinoma. However, data from prospective comparative studies are necessary to answer this question.\n One hundred one patients were included in a randomized prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic, and histologic assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1-18) in the medical treatment group and 6 years (range 1-18) in the surgical treatment group.\n Satisfactory clinical results (excellent to good) were achieved in 39 of the 43 patients (91%) undergoing medical treatment and in 53 of the 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed a significant decrease in the median percentage of total time with pH below 4, although 9 of the 58 patients (15%) showed pathologic rates of acid reflux. High-grade dysplasia appeared in 2 of the 43 patients (5%) in the medical treatment group and in 2 of the 58 patients (3%) in the surgical treatment group. In the latter, both patients presented with clinical and pH-metric recurrence. There was no case of malignancy after successful antireflux surgery.\n These results show that there are no differences between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful antireflux surgery proved to be more efficient than medical treatment in this sense, perhaps because it completely controls acid and biliopancreatic reflux to the esophagus.", "Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. 5-Aminlevulinic acid-induced photodynamic therapy and argon plasma coagulation have been shown to be effective for ablating Barrett's oesophagus, but a comparative trial of these two modalities has not been reported.\n To compare photodynamic therapy and argon plasma coagulation for the ablation of Barrett's oesophagus.\n A total of 68 patients (54 male, 14 female; median age 61) with Barrett's oesophagus were randomized to photodynamic therapy (n = 34) or argon plasma coagulation (n = 34). Photodynamic therapy was performed using 5-aminlevulinic acid (30 mg/kg) and red light. Argon plasma coagulation was administered at a power setting of 65 W. Multiple treatment sessions were performed, with follow-up to 24 months.\n All patients showed a macroscopic reduction in the area of Barrett's oesophagus. This was greatest in the argon plasma coagulation group with 33 of 34 (97%) ablated, compared with 17 of 34 (50%) in the photodynamic therapy group; in the remainder, there was a reduction in the length of Barrett's oesophagus (median 50%, range: 5-90). Buried glands were found in 24% of photodynamic therapy patients, and in 21% of argon plasma coagulation patients. The median follow-up is 12 months (range: 6-24).\n Photodynamic therapy and argon plasma coagulation are both effective for ablating Barrett's oesophagus. Argon plasma coagulation appears more effective than photodynamic therapy, but the impact of both on carcinoma development requires larger studies with long-term follow-up.", "Endoscopic mucosal ablation is a promising technique that is used to treat dysplastic Barrett's oesophagus. The purpose of this study was to investigate the efficacy and cost-effectiveness of two promising techniques, argon plasma coagulation (APC) and photodynamic therapy (PDT), in the ablation of dysplastic Barrett's oesophagus.\n Twenty-six patients with dysplastic Barrett's oesophagus (21 M, median age 60 years, median length 4 cm, 23 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD)) were randomized to APC: 13 patients, PDT: 13 patients. APC was performed at a power setting of 65 W and argon gas flow at 1.8 l/min in 1-6 sessions (mean 5). PDT was performed 48 h after intravenous injection of Photofrin 2 mg/kg with a 630 nm red laser light, 200 J/cm through a PDT balloon in one session. All patients received treatment with high-dose proton pump inhibitors. Cost analysis was undertaken and the results were assessed by endoscopy and biopsies at 4 months and 12 months after therapy.\n All patients in both groups showed a reduction in the length of Barrett's oesophagus. The median length of Barrett's oesophagus eradicated at the 4-month follow-up: APC 65%, PDT 57% and at the 12-month follow-up: APC 56%, PDT 60%. Dysplasia eradication at 4 months: APC 62%, PDT 77%, p = 0.03 (95% CI 0.66-0.96) and at 12 months APC 67%, PDT 77%. Buried columnar glands with intestinal metaplasia were seen in both groups, with one patient in the PDT arm developing adenocarcioma under the neo-squamous epithelium. Severe adverse events included APC 2/13 (15%) stricture, 1/13 (8%) odynophagia, chest pain and fever; PDT 2/13 (15%) photosensitivity, 2/13 (15%) stricture. PDT would cost an additional 266 pounds sterling for every percentage reduction in Barrett's length and 146 pounds sterling per percentage reduction in dysplasia compared with APC treatment.\n APC and PDT are equally effective in eradicating Barrett's mucosa, with PDT being the more expensive treatment. However, PDT is more effective in eradicating dysplasia and the extra benefits of PDT are generated at an extra cost. The occurrence of buried columnar glands and carcinoma warrants caution. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium to justify these interventions." ]

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[ "Cefazolin and netilmycin versus vancomycin and ceftazidime in the treatment of CAPD peritonitis.", "Treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis with intraperitoneal urokinase: a double-blind clinical trial.", "Is initial (24 hours) lavage necessary in treatment of CAPD peritonitis?", "A comparison between oral ciprofloxacin and intraperitoneal vancomycin and netilmicin in CAPD peritonitis.", "A comparison between oral ciprofloxacin and intra-peritoneal vancomycin and gentamicin in the treatment of CAPD peritonitis.", "Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial.", "Cefepime versus vancomycin plus netilmicin therapy for continuous ambulatory peritoneal dialysis-associated peritonitis.", "A prospective, randomized study of the comparative safety and efficacy of intraperitoneal imipenem versus vancomycin and netilmicin in the treatment of peritonitis on CAPD.", "Netilmycin and vancomycin in the treatment of peritonitis in CAPD patients.", "Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin.", "Comparison of vancomycin versus cefazolin as initial therapy for peritonitis in peritoneal dialysis patients.", "Intravenous or intraperitoneal vancomycin for the treatment of continuous ambulatory peritoneal dialysis associated gram-positive peritonitis?", "Cefazolin plus netilmicin versus cefazolin plus ceftazidime for treating CAPD peritonitis: effect on residual renal function.", "CAPD peritonitis: a prospective randomized trial of oral versus intraperitoneal treatment with cephradine.", "A randomized prospective comparison of oral versus intraperitoneal ciprofloxacin as the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis.", "A randomized prospective trial of three different regimens of treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis.", "A randomised prospective comparison of oral ofloxacin and intraperitoneal vancomycin plus aztreonam in the treatment of bacterial peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD).", "Is monotherapy with cefazolin or ofloxacin an adequate treatment for peritonitis in CAPD patients?", "The value of low-dose intraperitoneal immunoglobulin administration in the treatment of peritoneal dialysis-related peritonitis.", "A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD.", "Intraperitoneal vancomycin/oral pefloxacin versus intraperitoneal vancomycin/gentamicin in the treatment of continuous ambulatory peritoneal dialysis peritonitis.", "Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. The Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS).", "Role of intraperitoneal urokinase in acute peritonitis and prevention of catheter loss in peritoneal dialysis patients.", "Intraperitoneal ciprofloxacin and rifampicin versus cephradine as initial treatment of (C)APD-related peritonitis: a prospective randomized multicenter comparison (CIPPER trial).", "A comparison between intraperitoneal ciprofloxacin and intraperitoneal vancomycin and gentamicin in the treatment of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD).", "Intraperitoneal teicoplanin in the treatment of peritonitis associated with continuous ambulatory peritoneal dialysis.", "Tenckhoff catheter replacement or intraperitoneal urokinase: a randomised trial in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis.", "A prospective randomized comparison of single versus multidose gentamicin in the treatment of CAPD peritonitis.", "Intraperitoneal (IP) vancomycin therapy for CAPD peritonitis--a prospective, randomized comparison of intermittent v continuous therapy.", "A prospective, randomized trial of two antibiotic regimens in the treatment of peritonitis in CAPD patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin.", "Use of intraperitoneal urokinase for resistant bacterial peritonitis in continuous ambulatory peritoneal dialysis." ]

[ "In spite of several recommendations, choosing the initial antibiotic to treat continuous ambulatory peritoneal dialysis (CAPD) peritonitis remains difficult. In our prospective randomized study we attempted to evaluate the efficacy and safety of less toxic combinations of cephalosporins with vancomycin or netilmycin. From November 1993 to September 1996 we treated 52 episodes of peritonitis in 34 patients. Peritonitis was diagnosed according to the valid criteria. Patients were treated for 14 - 28 days with a combination of either cefazolin plus netilmycin or vancomycin plus ceftazidime. The most frequent bacteria causing peritonitis in the two groups were comparable. The efficacy of the cefazolin/netilmycin combination was 91.6% (22/24) without yeasts and 84.0% (21/25) in the vancomycin/ceftazidime combination. There were no statistically significant differences between the two otherwise efficient combinations of antibiotics. No side effects were observed. We believe that the frequent use of vancomycin could be avoided thus reducing the risks of resistance and ototoxicity.", "Resistant peritonitis in continuous ambulatory peritoneal dialysis (CAPD) is an indication for catheter removal, followed by interim haemodialysis and subsequent catheter replacement. This involves two surgical procedures using general anaesthetic and the availability of adequate hospital haemodialysis facilities. Urokinase is an alternative therapy but evidence of its effect is anecdotal and it has not been studied in a double-blind manner. Patients with resistant peritonitis (either no resolution of peritonitis within 4 days of appropriate antibiotic therapy or a third episode of peritonitis within 6 months) were randomized to receive intraperitoneal urokinase or placebo (saline) followed by 14 days of antibiotics in this double-blind prospective study. Treatment success was resolution of peritonitis within 4 days of giving urokinase/placebo (persistent infection) and no recurrence with the same organism for 6 months (recurrent infection). Twelve patients received urokinase and 12 placebo. Treatment was successful in 8/12 in the urokinase group and 1/12 in the placebo group (Fisher's exact test; P = 0.0047). Urokinase was successful in 8/12 patients with resistant peritonitis and significantly better than placebo. Urokinase is an effective and simple treatment that may avoid the need for catheter removal and interim haemodialysis in patients with resistant CAPD peritonitis.", "A randomized trial was conducted to examine the influence of initial lavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty-six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including either initial 24 hours lavage before resumption of routine CAPD schedule (prior standard approach) or continued prolonged exchanges as in routine CAPD schedule. Median time to solved infection (normalization of white cell count in dialysis effluent) was identical (3 days) in the two groups. Treatment success rate was found to be 72% in the group with initial lavage and 89% in the group with prolonged exchanges. The difference in treatment success (17%) in favour of continued CAPD schedule was not found significant (95% confidence limits--1% to 35%). The results suggest lavage to be of no clinical benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock.", "This report describes a prospective, randomized comparison of oral ciprofloxacin and intraperitoneal vancomycin/netilmicin in the treatment of 50 consecutive episodes of CAPD peritonitis in 35 patients. Successful cure of peritonitis was achieved in 76% of subjects taking oral ciprofloxacin and 72% of those given intraperitoneal antibiotics. Satisfactory concentrations of ciprofloxacin in dialysate were achieved in all patients. Failure of ciprofloxacin was due to persistence of an isolate of intermediate sensitivity (1), to persistence with acquisition of resistance (1), and to relapse/reinfection in the remaining four cases (with resistant or moderately sensitive strains in three cases). Ciprofloxacin was well tolerated in the majority of cases. A significant rise in serum creatinine was noted in almost all patients taking oral ciprofloxacin. The advantages of oral drug administration indicate that oral ciprofloxacin is the preferred first-line treatment of CAPD-associated peritonitis.", "Fifty-one patients were included in a prospective, randomized comparison of oral ciprofloxacin and intraperitoneal vancomycin/gentamicin in the treatment of CAPD peritonitis. Staphylococcal species accounted for 40% of the isolates with an equal incidence of Staphylococcus aureus and coagulase negative staphylococci. Although, overall, there was no significant difference between the regimens in outcome, ciprofloxacin was significantly less effective when peritonitis was due to coagulase negative staphylococci.", "Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD-related peritonitis.\n We performed an open-label, randomized control study comparing imipenem/cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate.\n We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively (p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups (p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively (p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group (p = 0.90).\n We concluded that monotherapy of imipenem/cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis.", "Cefepime is a cephalosporin with a broad spectrum of activity against most gram-positive and gram-negative pathogens. In this study, we attempted to compare the safety and efficacy of cefepime monotherapy against the potentially more toxic combination of vancomycin and netilmicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated bacterial peritonitis. Eighty-one consecutive CAPD patients who presented with peritonitis from January 1, 1998, to June 30, 2000, were recruited for study. Patients were randomized to be administered either intraperitoneal (IP) cefepime, 1 g once daily (group A), or intravenous vancomycin and netilmicin at conventional doses (group B) for 10 days. Bacterial growth was obtained in 52 episodes (66%), and pathogens identified included gram-positive organisms (30 episodes; 38%), gram-negative organisms (14 episodes; 18%), mixed organisms (2 episodes; 2.5%), and fungus (6 episodes; 8%). Eight patients were excluded after randomization for various reasons (6 patients, fungal peritonitis; 2 patients, wrong diagnoses). Because of the relatively low peritonitis rate after the use of a disconnect system, the sample size of this study was relatively small, giving a power of 0.45. There were no significant differences in primary response rates and cure rates (no relapse >28 days after completion of antibiotic therapy) between both groups of patients (group A versus group B, 82% [32 of 39 patients] versus 85% [29 of 34 patients] and 72% [28 of 39 patients] versus 76% [26 of 34 patients], respectively; P = not significant). No significant side effect was encountered in either group. Total peritonitis-related hospitalizations were 84 patient-days (1, 7, 8, 11, 20, and 37 patient-days) and 115 patient-days (3, 6, 9, 14, 21, 21, and 41 patient-days), whereas total costs per patient cure were estimated to be US $1,039 and US $1,371 in groups A and B, respectively. We conclude that once-daily 1-g IP cefepime monotherapy is a simple, safe, and cost-effective alternative to vancomycin and netilmicin therapy in the treatment of CAPD-associated bacterial peritonitis.", "nan", "This study was undertaken to evaluate: 1. The efficacy of netilmycin and vancomycin as combined first line antimicrobial regime, compared to cefuroxime, in the treatment of peritonitis. 2. To measure the levels of netilmycin and vancomycin in the serum and dialysate. 3. To report on the use of this combination over a one year period and compare it with that of cefuroxime used during the previous one year.", "To determine if intraperitoneal administration of vancomycin (a slowly absorbed antibiotic) improves the management of dialysis-associated peritonitis over that obtained by using cefazolin, an equally potent, rapidly absorbed antibiotic.\n A university operated teaching hospital, with patient treatment initiated at home.\n One hundred thirty-one patients trained to perform peritoneal dialysis (CAPD and CCPD) and followed at the University of Iowa Hospitals and Clinics Home Dialysis Treatment Center.\n Patients were prospectively allocated into groups adding either vancomycin 25 mgm/L, or cefazolin 50 mgm/L to their dialysate when signs or symptoms of peritonitis developed. Treatment results were analysed using chi-square testing.\n Compared to cefazolin, initial peritonitis therapy with vancomycin improved the peritonitis resolution rate [67% vs 81%; p = 0.008], reduced the incidence of hospital admissions [68% vs 48%; p = 0.001], and decreased the risk of superinfection [4% vs 0%; p = 0.039].\n Vancomycin appeared to be superior to cefazolin in the treatment of peritoneal dialysis associated peritonitis.", "The incidence of peritonitis ranges from 1 episode every 24 patient treatment months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.]. Gram-positive organisms account for over 80% of continuous ambulatory peritoneal dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one episodes of peritonitis in 30 patients studied over 2 years were evaluated. Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of peritonitis and were confirmed by cell count and culture. Baseline cell count, Gram stain, and cultures were obtained, with periodic follow-up. Patients were randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading dose, repeated on day 5 or day 8, depending on residual renal function, for 2 weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every exchange for 2 or 3 weeks, depending on culture results. All patients also received gentamicin 40 mg IP every day until the culture results were available. A similar randomized trial comparing vancomycin and cefazolin in the past used a lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Perit Dial /nt 1991; 11:31-7.]. Peritoneal dialysate fluid cultures revealed 31(60.7%) gram-positive organisms, 7(13.7%) gram-negative organisms, and 2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of peritonitis at our center was 1 episode every 42 patient treatment months. No case of VRE was noted. There was no statistical difference in clinical response or relapse rate for the two protocols. It was the authors' and nurses' observation that patient compliance and satisfaction was better with vancomycin, and the cost per treatment was 23% less than cefazolin. Based on these data we believe vancomycin should still be considered for first-line treatment of PD-associated peritonitis.", "A clinical and pharmacokinetic study was carried out to determine whether an intraperitoneal (IP) loading dose of vancomycin was as effective as an intravenous (IV) load in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated gram-positive peritonitis. Each patient continued a 14-day treatment on IP maintenance doses. All cases of peritonitis (10 in each group) were eradicated. Side effects occurred in 3 patients following IV vancomycin and in none following IP vancomycin. Serum and peritoneal vancomycin concentrations equilibrated fully and rapidly with each route. It is concluded that an IP loading dose of vancomycin, followed by IP maintenance doses, is as effective as and produces fewer side effects than an IV loading dose in the treatment of CAPD peritonitis.", "BACKGROUND. The International Society for Peritoneal Dialysis (ISPD) treatment guidelines for continuous ambulatory peritoneal dialysis (CAPD) peritonitis 2000 recommended the use of cefazolin plus ceftazidime as the initial empirical therapy in patients with residual renal function (RRF). However, this treatment regimen has not been compared with the conventional regimen of cefazolin plus netilmicin in prospective, randomized controlled trials.\n Stable CAPD patients who developed clinical evidence of peritonitis were randomized to receive intraperitoneal (i.p.) cefazolin plus netilmicin or cefazolin plus ceftazidime once daily in the long dwell for 14 days. For patients with RRF (>1 mL/minute) before entry into the study (N= 50), RRF and 24-hour urine volume were measured at days 1, 14, and 42 after commencement of i.p. antibiotic treatment.\n One hundred and two patients were recruited into the study. The primary cure rates of i.p. cefazolin plus netilmicin and cefazolin plus ceftazidime were 66.7% and 64.7%, respectively. The overall cure rate for the 2 treatment regimens was 82.3% for both. Seven patients (14%) from each treatment group required removal of the dialysis catheters due to treatment failure. Relapse of peritonitis occurred in 2 patients (4%) in both treatment groups. Thirty-six patients with RRF at baseline achieved primary cure of their peritonitis by the assigned antibiotics. In this subgroup of patients, their RRF and daily urine volume showed significant reduction at day 14 and returned to near baseline values at day 42. The degree of reduction in RRF and urine volume did not differ significantly between the patients treated with cefazolin plus netilmicin and cefazolin plus ceftazidime.\n Intraperitoneal cefazolin plus netilmicin and cefazolin plus ceftazidime have similar efficacy as empirical treatment for CAPD peritonitis. In CAPD patients with RRF, significant but reversible reduction in RRF and 24-hour urine volume could occur after an episode of peritonitis, despite successful treatment by i.p. antibiotics. The effect of i.p. cefazolin plus netilmicin, or i.p. cefazolin plus ceftazidime on RRF in CAPD patients with peritonitis does not appear to be different. Our findings do not support the routine use of cefazolin and ceftazidime as the empirical treatment for CAPD peritonitis.", "In a prospective randomized clinical trial 84 peritonitis episodes were treated with cephradine, either orally or intraperitoneally. No difference in treatment outcome between both groups could be demonstrated. In episodes caused by susceptible micro-organisms a good response was seen in 82% in the oral and 82% in the intraperitoneal groups. These clinical findings were supported by the demonstration of adequate cephradine concentrations in serum and dialysate after oral as well as after intraperitoneal administration. Altogether cephradine was given orally or intraperitoneally in 88 episodes of peritonitis as drug of first choice. In 52 a complete cure was obtained, in 36 another antibiotic was subsequently needed as soon as bacterial susceptibility was known. No patient deteriorated appreciably during the delay between the start of cephradine and the switch to another antibiotic. Of the 36 episodes 14, caused by methicillin-resistant Staphylococcus epidermidis, responded well initially to cephradine but relapsed later. Change to another antibiotic effected a complete recovery in all 14 cases. Of the remaining 22 episodes, 14 were cured by the other antibiotic, in eight the catheter had to be removed. Aminoglycosides could be avoided except for ten of the episodes. During peritonitis CAPD was continued, in 71% of the cases on an outpatient basis. Mortality due to peritonitis was absent. We conclude that oral cephradine can be used as drug of first choice in the initial treatment of CAPD peritonitis, because a good initial response was obtained in 66 (52 + 14) i.e. 75% of 88 episodes. However, complete cure by cephradine alone was achieved in only 60%.(ABSTRACT TRUNCATED AT 250 WORDS)", "The present study compared oral versus intraperitoneal (ip) ciprofloxacin (ciproxin) as primary treatment of bacterial peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) in a randomized, prospective trial. A total of 54 episodes in 46 patients were recruited for study. After excluding nonbacterial episodes and those not treated according to protocol, 48 episodes evenly divided between the two treatment arms were eligible for analysis. The primary cure rate was 41.7% and 66.7%, respectively, in the oral and ip treatment group. Half of those who failed or relapsed were due to infection with resistant, mostly gram-positive bacteria, which accounted for 79% of culture-positive episodes. Of the gram-positive isolates 42.3% were either resistant or intermediately susceptible to ciproxin compared to 16.7% of gram-negative isolates. The high level of bacterial resistance to ciproxin and treatment failure rate were related to the previous exposure to fluoroquinolones. Inadequate trough peritoneal drug levels also accounted for the failures in the ip but not the oral treatment group. We conclude that oral ciproxin is ineffective as a primary treatment of CAPD peritonitis in patients previously exposed to fluoroquinolones and that when administered ip, a dose of 50 mg/L instead of 25 mg/L of ciproxin should be used as maintenance in order to achieve adequate trough peritoneal drug levels.", "A randomized prospective study was undertaken in patients on continuous ambulatory peritoneal dialysis (CAPD) to evaluate the efficacy of three different antibiotic regimens for the treatment of peritonitis. There were 39 episodes in each treatment group. Patients were treated with intraperitoneal (IP) cephalothin (250 mg/L) and tobramycin (8 mg/L) in group 1, oral ofloxacin (400 mg loading followed by 300 mg daily) in group 2, and a combination of ofloxacin (400 mg followed by 300 mg daily) and rifampicin (300 mg daily). Treatment duration was 10 days. The average culture-positive rate was 75%. The overall cure rate was 80.6% with IP antibiotics, 78.4% with oral ofloxacin, and 81.1% with ofloxacin and rifampicin. After the exclusion of tunnel infections and episodes of peritonitis due to Pseudomonas and resistant organisms, the corresponding figures were 100%, 90.6%, and 93.7%, respectively. Side effects were minimal with IP treatment and with oral ofloxacin, but severe nausea and vomiting occurred in some cases with the combination of ofloxacin and rifampicin. It was concluded that oral ofloxacin is an acceptable first-line therapy for peritonitis in CAPD patients.", "Forty six patients who developed 48 episodes of peritonitis while on CAPD were randomised to receive either oral ofloxacin or intraperitoneal (i.p.) vancomycin/aztreonam. Three patients were excluded from analysis: 2 were transferred to other hospitals and 1 was later found to have candida peritonitis. Of the remainder, 22 episodes were treated with oral ofloxacin and 23 with i.p. vancomycin/aztreonam. The primary cure rate in the oral ofloxacin and i.p. vancomycin/aztreonam group was 77.3% and 87.5% respectively. There were 3 primary failures and 2 relapses in the former and 1 failure and 2 relapses in the latter group. Two of the 4 primary failures were peritonitis episodes secondary to infection with pseudomonas species. The total number of days of hospital stay was 48 and 58 respectively in the two groups. Analysis of the cost of treatment revealed that i.p. vancomycin/aztreonam was 30 times more expensive than oral ofloxacin. Despite a slightly higher cure rate with i.p. vancomycin/aztreonam, oral ofloxacin is a more cost-effective primary treatment of bacterial peritonitis in patients on CAPD especially in countries with a limited health budget.", "This prospective randomized study is an evaluation of efficacy of cefazolin and ofloxacin in 23 end-stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD) who experienced 38 episodes of peritonitis (P). Cefazolin was administered intraperitoneally: 1000 mg as loading dose and 250 mg every exchange as maintenance dose for ten days. Ofloxacin was given orally: first 300 mg, followed by ten daily doses of 200 mg. Microbes most frequently isolated from peritoneal effluent were Staphylococci (coagulase-negative in 55.3%, aureus in 7.9%), Acinetobacter (in 5.3%), Klebsiella (in 5.5%), and Micrococcus (in 5.3%). Used as monotherapy, we found the efficacy of both cefazolin and ofloxacin inadequate for treatment of P in CAPD patients (cefazolin 65%, ofloxacin 67%) (NS).", "Peritonitis is a major complication of continuous ambulatory peritoneal dialysis (CAPD). The value of immunomodulatory therapeutic approaches and, especially, methods aimed at augmenting opsonization in the treatment of peritoneal dialysis (PD)-related peritonitis is unclear. In this study, the effect of intraperitoneal (IP) immunoglobulin (Ig) usage, as an approach for strengthening opsonization, was evaluated in CAPD peritonitis.\n The study included 24 patients with CAPD peritonitis. The patients were divided into two groups, A and B, each consisting of 12 patients. There were no significant differences between the groups in terms of age, gender, CAPD duration, and peritonitis rate. Empiric antibiotic treatment was a 2-week IP ampicillin+sulbactam/netilmycin combination. Group B was additionally given low-dose IP IgG (2 mL = 320 mg) with every exchange. The dialysate leucocyte counts were obtained in both groups until the number was <100 cells/microL to monitor the response to peritonitis treatment.\n In group A, the number of exchanges done until the dialysate leucocyte counts decreased to <100/mL was 13.9 +/- 1.4 and for group B 6.6 +/- 0.4 (p<0.001). The reduction in neutrophils was significantly faster in group B compared to group A (p<0.001). The number of exchanges until abdominal pain completely disappeared was 12.5 +/- 1.7 in group A and 5.6 +/- 0.7 in group B (p<0.001).\n The results of this study show that low-dose, continuous IP IgG administration in the treatment of PD-related peritonitis is safe and effective in shortening the treatment time.", "To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD).\n A randomized multicenter prospective open-label comparative clinical study.\n University and Hospital Authority hospitals in Hong Kong.\n All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial.\n A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones.\n Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones.", "Sixty patients were enrolled in a prospective, randomized study to evaluate the efficacy of two different regimens for the empirical treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. At presentation, Group I received intraperitoneal vancomycin (1 g) and oral pefloxacin (400 mg b.i.d.), and Group II intraperitoneal vancomycin (1 g) and gentamicin (80 mg loading dose, followed by 15 mg/2 L). Treatment duration was 14 days. Despite randomization, Group I had significantly more patients with primary Candida peritonitis. When fungal peritonitis was excluded from analysis, there were no significant differences in the treatment success rate (Group I, 73.3% vs Group II, 80.0%, p = NS), number of relapses (Group I, 0 vs Group II, 1), and Tenckhoff catheter removal rates (Group I, 26.6% vs Group II, 16.6%, p = NS) between the two groups. The patients treated with pefloxacin had an increased incidence of nausea and vomiting. In selected situations oral pefloxacin may be a suitable substitute for intraperitoneal gentamicin as out-patient therapy for CAPD peritonitis.", "Intermittent intraperitoneal antibiotic administration appears as a practical and economical therapeutic concept in continuous peritoneal dialysis (CPD)-related peritonitis, but the equivalence of this principle with standard continuous treatment awaits confirmation by prospective, randomized clinical trials. This study evaluates the efficacy, safety, and clinical acceptance of an initial combination treatment including a glycopeptide (vancomycin or teicoplanin) and ceftazidime, each applied either intermittently or continuously, in a cohort of pediatric patients with CPD-related peritonitis. Patients randomized for continuous treatment received an intraperitoneal loading dose of glycopeptide and ceftazidime followed by maintenance doses added to each dialysate bag. In the intermittent treatment groups, the glycopeptide was administered in two loading doses 7 d apart, and ceftazidime during one dialysis cycle per day. Initial treatment response was evaluated after 60 h by the change in a Disease Severity Score and by the clinical decision to continue initial treatment. Of 152 patients observed for a total of 234 patient years, 90 patients developed 195 episodes of peritonitis (including 27 relapses within 4 wk after end of treatment). Dialysate cultures were positive in 83% of the episodes. In gram-positive peritonitis (79% of culture-positive cases), the primary success (overall 95%) and relapse rates (21%) were not different between continuous and intermittent, or between vancomycin and teicoplanin treatment. Oversensitivity reactions occurred in three and ototoxicity in one vancomycin-treated patient, whereas no such side effects were observed with teicoplanin. Residual renal function declined during peritonitis episodes regardless of treatment modality. In gram-negative peritonitis (18% of cases), intermittent ceftazidime treatment was less successful than continuous treatment according to clinical judgment (3 of 11 versus 10 of 14, P < 0.05), but not when rated by Disease Severity Score (8 of 11 versus 12 of 14). In conclusion, intermittent and continuous intraperitoneal treatment of CPD-related peritonitis with glycopeptides and ceftazidime is equally efficacious and safe when measured by objective clinical criteria. This contrasts with a strong tendency of clinicians to move from intermittent to continuous treatment in severe peritonitis.", "Some studies have demonstrated the efficacy and safety of intraperitoneal (i.p.) urokinase in the resolution of recurrent or relapsing peritonitis, while others have not. Most studies were small, and they varied in methodology. Furthermore, the role of i.p. urokinase in shortening the duration of peritonitis or in preventing recurrence after initial peritonitis has not been examined. In addition, no previous studies have examined the role of i.p. urokinase in preventing, after first infection, catheter loss due to unresolving (resistant) peritonitis. Over a period of 3 years, we prospectively randomized into two groups all peritoneal dialysis (PD) patients who developed a first episode of peritonitis. Group I (n = 40) received i.p. urokinase on the first day of diagnosis (5000 IU intraluminally in the peritoneal catheter and left for 4 hours before next exchange). Group II (n = 40) received no urokinase. The duration of peritonitis was assessed by daily PD fluid white blood cell (WBC) count. Indications for catheter removal were: persistent peritonitis after four days from initiation of antibiotic therapy, or peritonitis with multiple organisms, suggesting bowel perforation. No statistically significant difference was seen between the two groups in regard to primary cause of end-stage renal disease (ESRD), age, sex, race, weight, type of dialysis [continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), continuous cycling peritoneal dialysis (CCPD)], or duration of dialysis prior to first peritonitis. No statistically significant difference was seen between the two groups in the duration of peritonitis or in the severity of symptoms and signs of peritonitis. Neither was any difference seen in the peritonitis recurrence or relapse rate (10% in the urokinase group vs 7.5% in the control group). Nine patients lost their catheters (3 in the urokinase group: 1 Pseudomonas aeruginosa and 2 Candida tropicalis; 6 in the control group: 1 Klebsiella pneumonia, 1 enterococcus, 2 Pseudomonas aeruginosa, and 2 Candida tropicalis). The difference in the rate of catheter loss between the two groups was not statistically significant; it appeared to relate to the type of organism rather than to the response to urokinase. In conclusion, i.p. urokinase plays no significant role in shortening the course of peritonitis or in preventing recurrence or loss of the PD catheter. Loss of PD catheters in patients having their first peritonitis appears to be related primarily to the type of organism causing the infection.", "The initial treatment of peritonitis has evolved from single-agent to combination regimens. The initial response rates improved with these newer regimens but relapsing peritonitis continues to occur. For biofilm-embedded or intracellularly sequestrated bacteria, a combination of intracellularly- and biofilm-active agents such as ciprofloxacin and rifampicin might be beneficial. Many Dutch centers continue to use cephradine as initial treatment, claiming clinically adequate responses with this regimen. We compared the impact of these two regimens on outcome in patients who developed a new episode of peritonitis.\n Prospective randomized open trial.\n Multicenter study including 14 Dutch dialysis units.\n From October 1996 to October 1999, 367 patients from 14 centers were randomized to be treated with ciprofloxacin + rifampicin (CR; each 50 mg/L) or cephradine (C; 250 mg/L) in case of peritonitis. Of these 367 patients, 98 developed peritonitis, 44 of whom were treated with CR and 54 with C.\n Clinical response, divided into early (during the 2 weeks of therapy) and late (including the following 4 weeks) response. Success was defined as disappearance of all signs and symptoms by days 4-6, through day 42. Bacteriological response was either success (eradication) or failure (persistence, superinfection, or eradication with relapse/reinfection).\n The groups were comparable for age, sex, duration of continuous ambulatory/automated peritoneal dialysis, and occurrence of diabetes. Bacteriological cultures in both groups revealed predominantly gram-positive micro-organisms. Initial and late clinical successes were obtained in 27/54 and 20/54 episodes (50% and 37%) in the C group, and 33/44 and 28/44 episodes (75% and 63.6%) in the CR group (p = 0.021 and p = 0.019). Bacteriological success occurred in 29.6% in the C group, and in 59.1% in the CR group (p= 0.026), with failure in 46.3% and 18.2%, respectively. Peritonitis episodes were bacteriologically not evaluable in 24.1% of episodes in the C group and 22.7% of episodes in the CR group, due mostly to no growth in the initial culture.\n The CIPPER Trial showed ciprofloxacin + rifampicin to be superior to cephradine as empiric treatment of peritonitis.", "In a prospective, randomized, controlled trial in 40 patients, intraperitoneal ciprofloxacin was shown to be as effective as the currently recommended regimen of intraperitoneal vancomycin and gentamicin for the treatment of CAPD peritonitis. There was one treatment failure in the ciprofloxacin arm and four in the comparative arm. A single drug regimen is preferred by patients. The intraperitoneal route of administration of ciprofloxacin therapy has advantages over the oral route.", "The efficacy of teicoplanin in the treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was evaluated in a randomised comparison with vancomycin. The dosage regimen used was 50 mg of vancomycin or teicoplanin per 2 1 bag of dialysate for 48 h followed by 25 mg per bag for a further five days. Twelve episodes of peritonitis were studied. There was no significant difference in the bacteriological or clinical cure rates of either antibiotic.", "A randomised trial, comparing Tenckhoff catheter replacement as a one-stage procedure and i.p. urokinase, was undertaken in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis. In addition to appropriate i.p. antibiotic treatment, 17 patients received i.p. urokinase (5000 i.u.) on the second and fourth days of antibiotic treatment, and 14 patients underwent CAPD catheter replacement. An additional six patients also underwent catheter replacement following the recurrence of peritonitis after urokinase treatment. The subsequent recurrence rate of peritonitis following CAPD catheter replacement (5%) was significantly less than after urokinase (41%) (p less than 0.001). Fourteen patients remained free of peritonitis for at least three months after catheter replacement, and five patients were peritonitis-free following urokinase for this period.", "There is an increasing trend towards the use of aminoglycosides in a once-daily dose administration for the treatment of severe infections in nonrenal failure patients. The use of once-daily dose aminoglycoside therapy may be associated with a reduction in toxicity. We performed a prospective randomized study comparing once-daily versus multiple-dose gentamicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Seventy-three patients with 100 new episodes of peritonitis were enrolled in the study. At presentation of peritonitis, the patients were alternately assigned to receive either intraperitoneal gentamicin at a dose of 40 mg/2 L dialysate administered as a once-daily dose or gentamicin at a dose of 10mg/2 L dialysate administered 4 times per day. All patients also received intraperitoneal vancomycin at a dose of 1 g per week. There were no significant differences in the treatment success (88% vs 82%, p = NS) and relapse (18% vs 20%, p = NS) rates between the once-daily dose and multiple-dose groups. The mean trough serum gentamicin level was higher in the once-daily dose group compared to the multiple-dose group (0.75 +/- 0.72 vs 1.50 +/- 1.40 mg/L). In conclusion, gentamicin administered in a once-daily dose is as effective as multiple-dose administration in the treatment of CAPD peritonitis. The lower gentamicin level with once-daily dose administration may be associated with a reduction in aminoglycoside toxicity.", "The use of intraperitoneal (IP) vancomycin as initial, single agent therapy for gram positive and \"no organism\" continuous ambulatory peritoneal dialysis (CAPD) peritonitis is described, comparing continuous and intermittent administration schedules. \"Continuous\" therapy consisted of an IP 1-g loading dose of vancomycin followed by 30 mg/L dialysate effluent. \"Intermittent\" therapy consisted of 2 IP doses of 30 mg vancomycin/kg body weight--the initial dose delivered at diagnosis and the second dose 1 week later. All patients presenting with peritonitis (n = 90) were randomized to receive either continuous or intermittent vancomycin therapy. Patients in whom gram negative organisms and fungi were identified by microscopy and culture were transferred to therapy with a more appropriate antibiotic (n = 39). In the remainder (n = 51), CAPD peritonitis was treated solely with vancomycin (continuous, n = 21; intermittent, n = 30). Clinical resolution was seen in all patients, requiring a mean of 3.2 days for macroscopic clearing of dialysate effluent. Recurrence of peritonitis within 1 month of cessation of therapy was unusual and did not vary between treatment protocols (4/21 v 3/30; P = NS). There were no differences in observed side effects. Thus, IP vancomycin proved to be a useful single agent therapy for gram positive and no organism CAPD peritonitis. Therapy with two IP doses was effective and as safe as continuous IP vancomycin therapy, and therefore should replace other vancomycin administration schedules in the treatment of CAPD peritonitis.", "A multicentre, comparative, randomized study was performed to compare the efficacy and tolerability of two antibiotic regimens in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. After informed consent had been obtained, 68 patients were randomized prospectively to receive either teicoplanin plus tobramycin or cephalothin plus tobramycin. Patients were followed throughout the study and for up to 4 weeks after the end of treatment, when clinical and microbiological parameters were assessed again. The incidence of clinical failure was 4.6 times higher in the cephalothin plus tobramycin group than in the teicoplanin plus tobramycin group (7/28 versus 2/37; P < 0.05). There was no significant difference in bacterial eradication between the two groups. Local and systemic tolerability were good for both regimens. The study shows that teicoplanin plus tobramycin is more effective than cephalothin plus tobramycin and might become a 'first-line' treatment for peritonitis in CAPD patients.", "Intraperitoneal (IP) urokinase is a fibrinolytic agent that has been used in the adjunctive treatment of continuous ambulatory peritoneal dialysis (CAPD) and resistant and relapsing peritonitis. However, its efficacy and role in treating resistant CAPD bacterial peritonitis remain unclear and results from previous prospective studies have been conflicting. We prospectively randomized 88 CAPD patients with bacterial peritonitis resistant to initial empirical IP antibiotics into two groups: IP urokinase 60,000 IU and a placebo group. Patients were treated concomitantly with susceptible antibiotics according to culture results. Peritoneal dialysate grew pseudomonas aeruginosa in 13 patients (14.8%), non-pseudomonas bacteria in 63 patients (71.6%) and negative cultures in 12 patients (13.6%). For the clinical outcomes, there were no significant differences in the primary response rates (61.4 vs. 50%), relapse rates (9.1 vs. 13.6%), Tenckhoff catheter removal rates (22.7 vs. 29.5%) and mortality rates (6.8 and 6.8%) between the urokinase group and the controls (p=ns). Subgroup analysis of culture negative patients (n=12) also demonstrated no sgnificant benefit for urokinase treatment. No significant adverse effects were encountered with the IP urokinase instillation. Total median peritonitis-related length of hospitalization for the urokinase group and controls were 7 and 11 days, respectively (p=0.32). We concluded that IP urokinse plays no significant role as an adjuvant therapy in the treatment of bacterial CAPD peritonitis resistant to initial IP antibiotic therapy." ]

[ "2647025", "10932665", "2185680" ]

[ "Clean up varicose vein surgery--use a tourniquet.", "A prospective randomised trial of tourniquet in varicose vein surgery.", "Varicose vein surgery using a pneumatic tourniquet: reduced blood loss and improved cosmesis." ]

[ "A controlled randomised trial has been carried out to ascertain if there are tangible benefits from using a tourniquet when avulsing varicose veins during routine varicose vein surgery. Twenty-six patients have been studied. Twenty limbs were operated on with a tourniquet and 20 limbs without a tourniquet. The mean weight of varices excised was 2.76 g (range 0.51-8.79 g) with a tourniquet and 2.68 g (0.77-11.27 g) without a tourniquet (NS, Wilcoxon's rank sum test). Mean blood loss was 16 ml (0-136 ml) with a tourniquet and 107 ml (16-581 ml) without a tourniquet (P less than 0.01, Wilcoxon's rank sum test). The mean time to complete avulsions was 38 min with a tourniquet and 35 min without a tourniquet (NS, Student's t test). The tangible benefits of a tourniquet are limited to the saving of blood which can amount to 500 ml per leg. Losses could amount to 1 litre in bilateral cases operated upon without tourniquet. The method is simple, provides a clean operating field and should be more widely used.", "A prospective randomised trial of 50 patients was carried out to assess the autoclavable Lofquist cuff (Boazal, Sweden) as a tourniquet in varicose vein surgery and determine the effect on bleeding, bruising, cosmesis and patient pain and activity. Patients undergoing unilateral long saphenous vein ligation, stripping and avulsions were randomised to tourniquet or no tourniquet. Lofquist cuffs were applied after inflation to 120 mmHg to the upper thigh for the duration of the surgery. Varicose vein grade, duration of surgery, blood loss, extent of bruising at 7 days, pain and activity scores over the first week, and wound complications and cosmetic result at 6 weeks were recorded. Patients' age, sex, and varicose vein grade were similar in the two groups. Peroperative blood loss (median, range) was significantly reduced in the tourniquet group (0 ml, 0-20 ml) compared to the no tourniquet group (125 ml, 20-300; P < 0.01). Operative time and thigh bruising (median, range) were also reduced in the tourniquet group (30 min, 11-47 min; 72 cm2, 30-429 cm2), respectively, compared to the no tourniquet group (37 min, 18-50 min; 179 cm2, 24-669 cm2) both (P < 0.01). There was no difference in pain and activity scores in the two groups and cosmetic results were also similar. The use of the Lofquist cuff tourniquet during varicose vein surgery reduces peroperative blood loss, operative time and postoperative bruising without any obvious drawbacks.", "A prospective controlled randomised study has been performed of 100 consecutive patients undergoing varicose vein surgery. One group underwent saphenofemoral flush ligation and multiple lower leg avulsions with the leg exsanguinated with a Rhys-Davies cuff, and ischaemia maintained with a pneumatic tourniquet. The other group underwent identical surgery but with a 30 degree head down tilt only. Blood loss was significantly less (13.5 +/- 12 ml vs 133 +/- 78 ml; P less than 0.01) and postoperative cosmesis was significantly improved in patients in the tourniquet group. Operating time was similar (27 +/- 11 min vs 30 +/- 13 min) in the two groups." ]

[ "11272970", "2706885" ]

[ "A comparison of continuous infusion and intermittent flushing methods in peripheral intravenous catheters in neonates.", "Heparin lock intravenous line. Use in newborn infants. A controlled trial." ]

[ "The purpose of this study was to compare two methods of maintaining peripheral intravenous devices in neonates: continuous infusion (CI) and intermittent flushing (IF). There was no significant difference in the mean duration of patency between the two groups, but there was a significant difference with respect to reasons for removal or loss of patency. The main reason for removal in the CI group was infiltration or phlebitis, and in the IF group the reason was occlusion.", "The heparin lock technique has been available for parenteral access in older children and adults but has not yet been described for use in newborns. We randomized 39 newborns who needed parenteral medication in the intermediate care nursery to receive a heparin lock catheter (17) or an intravenous line kept patent by continuous low infusion rate (22). There were no differences between study groups with regard to birthweight, gestational age, or distribution of diagnoses. Infants in the heparin lock group were enrolled in the study on average 1 day longer than the continuous intravenous group (p less than 0.05). Subcutaneous infiltration occurred twice as frequently with the continuous intravenous line (p = 0.0015), and the life span was significantly less than heparin lock (1.0 +/- 0.5 days versus 2.1 +/- 1.0 days, p = 0.0003). Infants with continuous intravenous lines received approximately 20 ml/kg/day greater quantity of fluid (p less than 0.0001). There was no difference between groups with regard to mean heparin activity level. None of the infants developed hemorrhagic complications, thrombophlebitis, or documented nosocomial infection. Nurses significantly favored heparin locks over continuous intravenous lines for ease of use. The heparin lock technique is a safe and reasonable alternative to a continuous low infusion intravenous line for administering parenteral medications to intermediate care newborns." ]

[ "2196353", "9469683", "6620024", "3889258", "6842336" ]

[ "Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia.", "Comparison of 6-hour infusion versus bolus furosemide in premature infants.", "Furosemide acutely decreases airways resistance in chronic bronchopulmonary dysplasia.", "Controlled trial of furosemide therapy in infants with chronic lung disease.", "Pulmonary effects of furosemide in preterm infants with lung disease." ]

[ "To test the hypothesis that alternate-day administration of furosemide will result in a sustained improvement in pulmonary function without causing alterations in electrolyte or mineral homeostasis, we conducted a randomized, double-blind, placebo-controlled study of 11 hospitalized, oxygen-dependent, spontaneously breathing infants with chronic bronchopulmonary dysplasia. Infants were randomly selected to receive either furosemide, 4 mg/kg in two divided doses on alternate days orally, or placebo for 8 days, followed by crossover to the alternate-therapy for an additional 8-day period. The two study periods were separated by a 48-hour washout period. Dynamic compliance, total pulmonary resistance, the concentration of electrolytes in serum, and the concentrations of calcium and creatinine in urine were measured on nontreatment days. Alternate-day furosemide therapy increased dynamic lung compliance by 76 +/- 112% and decreased total pulmonary resistance by 20 +/- 39%, compared with placebo (both variables p = 0.032). Alternate-day furosemide therapy did not result in increased urine output, electrolyte abnormalities, or increased urinary calcium excretion. We conclude that this simplified treatment regimen may be useful in the management of infants with chronic bronchopulmonary dysplasia. The results support our previous speculation that furosemide improves pulmonary function by mechanisms unrelated to its diuretic properties.", "To compare the renal, hemodynamic, and pulmonary effects of a 6-hour infusion of furosemide versus conventional bolus administration in premature infants.\n Prospective, blinded, placebo-controlled, randomized study.\n Two level III, university-based neonatal intensive care units.\n Thirty premature infants with significant lung disease, requiring furosemide after a red cell infusion.\n Infants received furosemide 1 mg/kg over 2 minutes, followed by a 6-hour placebo infusion, or a small loading dose of 0.1 mg/kg, followed by a slow infusion of 0.9 mg/kg over 6 hours. Serum and urine were collected to determine percentage fractional excretion of sodium (FENa).\n Urine output and blood pressure were measured every 2 hours after furosemide administration. Percentage FENa was measured immediately before furosemide and compared with pooled urine from an 8-hour collection after furosemide administration. Serum sodium, creatinine, and calcium were measured before and 24 hours after drug administration. Mean airway pressure and percentage inspired oxygen were compared before, 1-4 hours after, and 4-12 hours after drug administration. No significant differences were detected between the two methods of drug administration.\n Our data suggest that a 6-hour infusion of furosemide does not offer substantial clinical advantage over conventional bolus administration in premature infants when focusing on urine output, blood pressure, FENa, or pulmonary effect.", "We studied the effects of furosemide on pulmonary mechanics in 10 infants with bronchopulmonary dysplasia aged 41 +/- 1 (SE) weeks post-conception, gestational age at birth 30 +/- 1 wk, birth weight 1370 +/- 200 gm. Thoracic gas volume, airways resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured using an esophageal balloon. Infants with BPD had greater Raw, lower SGaw, and lower Cdyn than did 16 normal control infants. Within one hour after administration of furosemide 1 mg/kg IV to infants with BPD, Raw fell 36 +/- 13%, SGaw increased 84 +/- 22%, and Cdyn increased 54 +/- 13%; TGV did not change. Diuretic treatment of BPD in infants is associated with rapid, short-term improvement in Raw and Cdyn.", "To study the effects of furosemide therapy in infants with chronic lung disease (CLD), a double-blind controlled trial was designed. Seventeen infants with evidence of CLD (oxygen requirements greater than 30% at greater than 3 weeks of age and chest radiographic findings consistent with CLD) were studied. Pulmonary function was measured immediately before, and after 48 hours and 7 days of treatment with furosemide (1 mg/kg/12 hr intravenously or 2 mg/kg/12 hr orally) or placebo. Clinical status improved in six of seven infants who received furosemide and in two of 10 infants who received placebo (P less than 0.002). In the furosemide group, ventilator and oxygen requirements decreased (P less than 0.003); minute ventilation, alveolar ventilation, and dynamic compliance increased; and venous admixture decreased (P less than 0.05). There were no significant changes in the placebo group. Our findings suggest that furosemide significantly improves lung function during therapy in infants with CLD and allows earlier weaning from ventilatory support and supplemental oxygen.", "Twenty preterm infants recovering from respiratory distress syndrome at 1 week of age were randomized in this study either to a control or a treatment group. Those treated received a single daily dose of furosemide (1 mg/kg) intravenously. Pulmonary compliance was observed to improve significantly at two hours in the treated group, as compared with that in the controls. The calculated alveolar-arterial oxygen gradient was noted to decrease two hours after furosemide and to remain decreased over the four-day period in the treated group. This improvement in lung function was not secondary to diuresis in the infants treated with furosemide. We conclude that furosemide may have a direct pulmonary effect and improve lung function acutely as well as with chronic administration." ]

[ "2563465", "15231974", "10969126", "12897272", "11309632", "17229952", "16093466" ]

[ "Screening for otitis media with effusion in preschool children.", "Tympanic membrane abnormalities and hearing levels at the ages of 5 and 6 years in relation to persistent otitis media and tympanostomy tube insertion in the first 3 years of life: a prospective study incorporating a randomized clinical trial.", "The effect of ventilation tubes on language development in infants with otitis media with effusion: A randomized trial.", "Otitis media and tympanostomy tube insertion during the first three years of life: developmental outcomes at the age of four years.", "Effect of early or delayed insertion of tympanostomy tubes for persistent otitis media on developmental outcomes at the age of three years.", "Tympanostomy tubes and developmental outcomes at 9 to 11 years of age.", "Developmental outcomes after early or delayed insertion of tympanostomy tubes." ]

[ "1439 Dutch children were included in a randomised trial to evaluate the efficacy of preschool screening for otitis media with effusion (OME) by 3-monthly tympanometry. Children with bilateral OME on two consecutive occasions were referred for further investigation and then, if parents gave their consent, allocated at random to treatment or non-treatment groups. The effect of childhood screening for OME and subsequent treatment was evaluated by assessment of language performance; no benefit was found, mainly because of the large degree of spontaneous recovery.", "One current practice guideline recommends myringotomy with tympanostomy tube insertion (M&T) for young children in whom middle-ear effusion (MEE) has persisted for 3 months, and another recommends the procedure after MEE has persisted for 4 to 6 months provided that a bilateral hearing loss of > or=20 dB is present. Sequelae of M&T are not uncommon, but the extent to which these sequelae are attributable to M&T itself or to the middle-ear disease that prompted the procedure or to both has not been clear. Our objective in the present study was to examine the prevalence of various tympanic membrane (TM) abnormalities in otherwise healthy children at the age of 5 years and hearing levels at the age of 6 years in relation to persistent MEE and M&T in the children's first 3 years of life.\n In a prospective study of child development in relation to early-life otitis media, we randomly assigned 429 children who met specified criteria regarding the persistence of MEE in their first 3 years of life to undergo M&T either promptly (the \"early-treatment\" group) or after a defined extended period if MEE remained present (the \"late-treatment\" group). We also followed a representative sample of 241 children who ranged from having no MEE to having MEE whose cumulative duration fell just short of meeting randomization criteria for the clinical trial (the \"nontrial\" group). Most of the children in each group underwent both otomicroscopic examination at the age of 5 years and audiometric testing at the age of 6 years, at times when they were free of MEE. Among these children, M&T had been performed in 82.3% of those in the early-treatment group, 38.1% of those in the late-treatment group, and 3.0% of those in the nontrial group.\n At the age of 5 years, we found 1 or more types of TM abnormality in 1 or both ears in 70.7%, 42.5%, and 9.5% of the children in the early-treatment, late-treatment, and nontrial groups, respectively. Within the 3 groups, however, among children who received tubes, the proportions who had an abnormality of some type were similar, namely, 82.6%, 80.4%, and 83.3%, respectively. The corresponding proportions among children who had not received tubes were 15.4%, 19.3%, and 7.2%, respectively. Segmental atrophy and tympanosclerosis were the most common abnormalities found. At the age of 6 years, mean pure-tone average audiometric thresholds in the early-treatment, late-treatment, and nontrial groups, respectively, were 6.18 dB, 5.49 dB, and 4.63 dB in left ears and 6.17 dB, 6.02 dB, and 4.32 dB in right ears. The thresholds in the early- and late-treatment groups did not differ significantly, but the thresholds in the early- and late-treatment groups were each significantly higher than in the nontrial group. Within the early- and late-treatment groups, we found no significant relation between hearing levels and the presence or type of TM abnormalities.\n In otherwise healthy children who have persistent MEE during their first 3 years of life, ready resort to M&T results in far more TM abnormalities at age 5 than does selective management in which most children do not receive the procedure. With these differing approaches, however, hearing levels at age 6 do not differ. Regardless of whether children with persistent early-life MEE receive M&T, they have more TM abnormalities at age 5 and negligibly poorer hearing at age 6 than do children who had less or no otitis media. Longer term otologic and audiologic outcomes of persistent early-life MEE and of M&T remain to be determined. In view of 1) the present findings and the remaining uncertainties concerning sequelae, 2) the fact that M&T involves certain immediate risks--albeit minimal--and substantial cost, and 3) previously reported findings in the study's randomized clinical trial that show no developmental advantage at ages 3 and 4 years accruing from children's having received prompt M&T, a prolonged period of watchful waiting seems desirable in otherwise healthy children who are younger than 3 years and have persistent, asymptomatic MEE that is not complicated by sensorineural or severe conductive hearing loss, balance dysfunction, or severe TM retraction.", "To study the effectiveness of ventilation tubes on the language development in infants with persistent otitis media with effusion (OME). All existing studies addressed children 3 years of age or older. Currently, OME is detected and treated with ventilation tubes at a younger age. Because of the critical relationship between age, hearing, and language development, we conducted a study of the effects of ventilation tubes on language development in infants 1 to 2 years old with persistent OME.\n A multicenter, randomized, controlled trial (embedded in a cohort) with 2 treatment arms: 1) treatment with ventilation tubes (VT group; n = 93); or 2) with a period of watchful waiting (WW group; n = 94). Hearing loss and expressive and comprehensive language were assessed every 6 months, while tympanometry and otoscopy were performed every 3 months. Other factors with potential influence on language development were also included: adenoidectomy, hospital, attending day care, sex, age at randomization, educational level of the mother, upper respiratory infections, and the native country of the parents and older siblings. The trial was designed to allow for the detection of a mean difference in language development of 3 months or more between children allocated to the VT and WW groups.\n No relevant differences were found in expressive or comprehensive language between the 2 groups after adjustment for educational level of the mother, IQ of the child, and differences at baseline. A principal component analysis showed that in the VT group, the children with frequent complaints improved 1.6 months more in comprehensive language than those with no or some complaints. The children with favorable language stimulation, however, did not improve more than the children with less favorable stimulation. No differences were found for expressive language among the various clusters. The probability to improve >3 months in comprehensive language was.48 (95% confidence interval [CI]:.29-.68) for children with highly educated mothers versus.09 (95% CI:.02-.30) for children whose mothers had a low educational level. In the WW group, these changes were.30 (95% CI:.14-.53) and.14 (95% CI:.04-.35), respectively. The probability to improve >4 months in expressive language was.52 (95% CI:.32-.71) for children with highly educated mothers versus.06 (95% CI:.01-.31) for children whose mothers had a low educational level. In the WW group these changes were.42 (95% CI:.23-.64) and.11 (95% CI:.03-.35), respectively. In addition, there were delays in expressive language in both groups compared with their age expected values. The comprehensive language of the children who were effusion-free during the follow-up (n = 54) improved 1.5 months (95% CI: -.2-3.2) more than that of the children who had persistent effusion during the entire follow-up (n = 28). No differences were found for expressive language development. Disregarding the intervention contrast, improvements in hearing seemed to be related to improvements in language development, especially in verbal comprehension.\n In this study, we used the Reynell, Schlichting, and Lexi tests to study the relation between early persistent OME and language development. These tests are directly related to normal language, widely accepted, and validated. It cannot be ruled out that more specific measures such as auditory perception tests would have produced more differences between groups, but the focus was on general language development. A total of 10 children in the WW group received treatment with ventilation tubes during follow-up. A further 11 children dropped out during the trial. A sensitivity analysis with the 10 children who received ventilation tubes did not change the results, and baseline differences were not found between the 11 children who dropped out and those who completed the trial.\n In the total group of infants with persistent OME, ventilation tubes did not h", "In a long-term, prospective study, we set out to determine whether otitis media in the first 3 years of life persisting for periods currently considered developmentally threatening actually results in later impairments of children's cognitive, language, speech, or psychosocial development; whether prompt insertion of tympanostomy tubes prevents or lessens any such impairments; and whether, irrespective of causality, associations exist between persistent early-life otitis media and later developmental impairments. This report describes findings in study participants at the age of 4 years.\n We enrolled 6350 healthy infants from 2 to 61 days of age at urban hospitals and 2 small-town/rural and 4 suburban private pediatric practices. We regularly evaluated the children for the presence of middle-ear effusion (MEE) throughout their first 3 years of life by pneumatic otoscopy, supplemented by tympanometry; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated children for otitis media according to specified guidelines. In the clinical trial component of the study, we randomly assigned 429 children who met specified minimum criteria regarding the persistence of MEE to undergo tympanostomy tube insertion either promptly or after a defined extended period if MEE remained present. In the associational component of the study, we selected a representative sample of 241 children who ranged from having no MEE to having MEE the cumulative duration of which fell just short of meeting randomization criteria for the clinical trial. In 397 (92.5%) of the children in the clinical trial and in 234 (97.1%) of the children in the representative sample, we assessed cognitive, language, speech, and psychosocial development at the age of 4 years, using formal tests, conversational samples, and parent questionnaires.\n In children in the randomized clinical trial, there were no statistically significant differences in mean (+/-standard deviation) scores (higher denotes more favorable) favoring the early-treatment group over the late-treatment group on the General Cognitive Index of the McCarthy Scales of Children's Abilities (97 +/- 14 and 98 +/- 14, respectively); the Peabody Picture Vocabulary Test-Revised, a measure of receptive language (90 +/- 15 vs 92 +/- 16); the Nonword Repetition Test, a measure of phonological memory (66 +/- 12 vs 70 +/- 12); the Number of Different Words, a measure of word diversity (150 +/- 34 vs 150 +/- 31); the Mean Length of Utterance in Morphemes, a measure of sentence length and grammatical complexity (3.4 +/- 0.8 vs 3.4 +/- 0.7); or the Percentage of Consonants Correct-Revised, a measure of speech-sound production (92 +/- 5 vs 93 +/- 5). There were also no significant differences in ratings (higher denotes less favorable) on the Parenting Stress Index-Short Form (Total Stress scores: 68 +/- 18 vs 65 +/- 17) or the Child Behavior Checklist (Total Problem T scores: 50 +/- 10 vs 49 +/- 10). In the associational component of the study, correlations between the children's durations of MEE and their developmental outcomes were generally weak and, in most instances, nonsignificant. Exceptions, after adjustment for sociodemographic variables and for hearing thresholds at the time of developmental testing, consisted of a significant negative correlation between children's cumulative durations of MEE in their first 3 years of life and scores on the McCarthy Verbal subscale, and significant positive correlations between durations of MEE and scores on 2 measures of parent-child stress. The percentage of variance in these scores explained by time with MEE beyond that explained by sociodemographic variables ranged from 1.6% to 3.3%. In both the randomized clinical trial and the associational component, sociodemographic variables seemed to be the most important factors influencing developmental outcomes, and in both components, the results at 4 years of age were consistent with the results that had been obtained at 3 years of age.\n In otherwise healthy children who are younger than 3 years and have persistent MEE within the duration limits that we studied, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at 4 years of age. In such children, persistent MEE within the duration limits that we studied is negligibly associated with and probably does not affect developmental outcomes at 4 years of age.", "A main indication for the insertion of tympanostomy tubes in infants and young children is persistent otitis media with effusion, reflecting concern that this condition may cause lasting impairments of speech, language, cognitive, and psychosocial development. However, evidence of such relations is inconclusive, and evidence is lacking that the insertion of tympanostomy tubes prevents developmental impairment.\n We enrolled 6350 healthy infants from 2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before the age of three years 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted either as soon as possible or up to nine months later if effusion persisted. In 402 of these children we assessed speech, language, cognition, and psychosocial development at the age of three years.\n By the age of three years, 169 children in the early-treatment group (82 percent) and 66 children in the late-treatment group (34 percent) had received tympanostomy tubes. There were no significant differences between the early-treatment group and the late-treatment group at the age of three years in the mean (+/-SD) scores on the Number of Different Words test, a measure of word diversity (124+/-32 and 126+/-30, respectively); the Percentage of Consonants Correct-Revised test, a measure of speech-sound production (85+/-7 vs. 86+/-7); the General Cognitive Index of McCarthy Scales of Children's Abilities (99+/-14 vs. 101+/-13); or on measures of receptive language, sentence length, grammatical complexity, parent-child stress, and behavior.\n In children younger than three years of age who have persistent otitis media, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at the age of three years.", "Developmental impairments in children have been attributed to persistent middle-ear effusion in their early years of life. Previously, we reported that among children younger than 3 years of age with persistent middle-ear effusion, prompt as compared with delayed insertion of tympanostomy tubes did not result in improved cognitive, language, speech, or psychosocial development at 3, 4, or 6 years of age. However, other important components of development could not be assessed until the children were older.\n We enrolled 6350 infants soon after birth and evaluated them regularly for middle-ear effusion. Before 3 years of age, 429 children with persistent effusion were randomly assigned to undergo the insertion of tympanostomy tubes either promptly or up to 9 months later if effusion persisted. We assessed literacy, attention, social skills, and academic achievement in 391 of these children at 9 to 11 years of age.\n Mean (+/-SD) scores on 48 developmental measures in the group of children who were assigned to undergo early insertion of tympanostomy tubes did not differ significantly from the scores in the group that was assigned to undergo delayed insertion. These measures included the Passage Comprehension subtest of the Woodcock Reading Mastery Tests (mean score, 98+/-12 in the early-treatment group and 99+/-12 in the delayed-treatment group); the Spelling, Writing Samples, and Calculation subtests of the Woodcock-Johnson III Tests of Achievement (96+/-13 and 97+/-16; 104+/-14 and 105+/-15; and 99+/-13 and 99+/-13, respectively); and inattention ratings on visual and auditory continuous performance tests.\n In otherwise healthy young children who have persistent middle-ear effusion, as defined in our study, prompt insertion of tympanostomy tubes does not improve developmental outcomes up to 9 to 11 years of age. (ClinicalTrials.gov number, NCT00365092 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "To prevent later developmental impairments, myringotomy with the insertion of tympanostomy tubes has often been undertaken in young children who have persistent otitis media with effusion. We previously reported that prompt as compared with delayed insertion of tympanostomy tubes in children with persistent effusion who were younger than three years of age did not result in improved developmental outcomes at three or four years of age. However, the effect on the outcomes of school-age children is unknown.\n We enrolled 6350 healthy infants younger than 62 days of age and evaluated them regularly for middle-ear effusion. Before three years of age, 429 children with persistent middle-ear effusion were randomly assigned to have tympanostomy tubes inserted either promptly or up to nine months later if effusion persisted. We assessed developmental outcomes in 395 of these children at six years of age.\n At six years of age, 85 percent of children in the early-treatment group and 41 percent in the delayed-treatment group had received tympanostomy tubes. There were no significant differences in mean (+/-SD) scores favoring early versus delayed treatment on any of 30 measures, including the Wechsler Full-Scale Intelligence Quotient (98+/-13 vs. 98+/-14); Number of Different Words test, a measure of word diversity (183+/-36 vs. 175+/-36); Percentage of Consonants Correct-Revised test, a measure of speech-sound production (96+/-2 vs. 96+/-3); the SCAN test, a measure of central auditory processing (95+/-15 vs. 96+/-14); and several measures of behavior and emotion.\n In otherwise healthy children younger than three years of age who have persistent middle-ear effusion within the duration of effusion that we studied, prompt insertion of tympanostomy tubes does not improve developmental outcomes at six years of age.\n Copyright 2005 Massachusetts Medical Society." ]

[ "7752296", "14504022", "9313020", "7616334", "17315407", "11341854", "10716102", "10891632", "10529020" ]

[ "Clonidine and opiate receptor antagonists in the treatment of heroin addiction.", "The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial.", "Three methods of opioid detoxification in a primary care setting. A randomized trial.", "Primary care-based ambulatory opioid detoxification: the results of a clinical trial.", "A comparison of rapid (opioid) detoxification with clonidine-assisted detoxification for heroin-dependent persons.", "The impact of naloxone/lofexidine combination treatment on the opiate withdrawal syndrome.", "Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance.", "Naltrexone and lofexidine combination treatment compared with conventional lofexidine treatment for in-patient opiate detoxification.", "Naltrexone shortened opioid detoxification with buprenorphine." ]

[ "Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists. One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with (a) clonidine only, (b) clonidine and naltrexone, (c) clonidine and naloxone, and (d) placebos. Treatment results, emotional and behavioral changes, and involvement in psychosocial programs were evaluated after a 6-month follow-up. Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms, there was, in the group of patients treated with clonidine and naltrexone together, a low percentage of catabolites in urine and an improvement in mood and family relationships. Furthermore, the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs, and even their relatives demonstrated more interest in the recovery program. A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone.", "The efficacy of lofexidine/naloxone was compared with lofexidine/placebo in a double-blind, randomized, placebo-controlled trial in 89 opiate-dependent patients. There were no significant differences between the two groups in the proportion of patients completing detoxification or in the length of stay. Patients in the active naloxone group demonstrated gradual reductions in levels of withdrawal and craving over the detoxification period. At completion of detoxification, patients who received naloxone maintained a level of withdrawal consistently lower than that in the placebo group; however, naloxone did not substantially accelerate the resolution of the withdrawal syndrome. Implications for future research are discussed.", "Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients.\n To compare three pharmacologic protocols for opioid detoxification in a primary care setting.\n Randomized, double-blind clinical trial with random assignment to treatment protocols.\n A free-standing primary care clinic affiliated with drug treatment programs.\n 162 heroin-dependent patients.\n Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine.\n Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms.\n Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone.\n Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.", "To determine the feasibility of primary care-based ambulatory opioid detoxification (AOD) using two protocols: clonidine and clonidine plus naltrexone.\n The Central Medical Unit (CMU)--a freestanding primary care medical clinic staffed by physicians and nurse practitioners.\n Injection drug users (IDUs) seeking substance abuse treatment between the ages of 18 and 50 years who were addicted to opioids (e.g., heroin) and not currently in drug treatment.\n In the clonidine protocol, clonidine was administered every 4 hours \"as needed\" for up to 12 days. In the clonidine plus naltrexone protocol, clonidine was administered and naltrexone was administered in increasing doses over five days. Both protocols included \"adjuvant\" medications for muscle cramps, insomnia, and vomiting. Successfully detoxified patients were referred to ongoing drug treatment.\n A prospective nonrandomized clinical trial.\n One hundred forty opioid-addicted IDUs were referred to the medical clinic for AOD. Among the 125 patients who enrolled in the study, 57 selected clonidine and 68 selected clonidine/naltrexone. The treatment groups (clonidine vs clonidine/naltrexone) were similar at baseline with respect to: age at first heroin use (21 years vs 23 years), mean admission opioid craving score (45/100 vs 49/100), and withdrawal symptom score (19/72 vs 18/72). Overall, 70% (88/125) of the AODs were successful, including 42% (24/57) for clonidine and 94% (64/68) for clonidine/naltrexone (p < 0.001).\n This study suggests that primary care-based AOD can be safely and effectively carried out by primary care providers and that clonidine/naltrexone may be more effective in this setting than is clonidine alone. Ambulatory opioid detoxification can give internists a larger role in initiating drug treatment for IDUs who are addicted to opioids.", "This study compares two methods of detoxification available to heroin users in Western Australia: clonidine-assisted detoxification (CD) or clonidine-naloxone precipitated withdrawal under sedation (rapid opioid detoxification [ROD]). Oral naltrexone was made available to all participants following detoxification. Eighty heroin-dependent persons were randomly assigned to either ROD or CD. Most undertaking ROD commenced and completed this treatment. Less than one-third undertaking CD completed this treatment. There was no significant difference in those treated by CD or ROD in subjective assessment of degree or duration of pain, severity of withdrawal and craving, nor was there an increase in the withdrawal sequelae after treatment. Induction of oral naltrexone following ROD was greater, but oral naltrexone compliance levels and abstinence from heroin four weeks following detoxification were similar between ROD and CD groups. The level of patient satisfaction between the two treatments was also similar. The authors discuss why ROD is considered more effective than CD.", "Clinical studies in opiate-dependent patients suggest that detoxification treatment with opiate antagonists may accelerate the resolution of the opiate withdrawal syndrome, permitting early induction onto naltrexone maintenance treatment. The present open study compared the clinical efficacy of daily naloxone injections in conjunction with lofexidine, with conventional lofexidine monotherapy, in 49 polysubstance-misusing opiate-dependent patients. Overall, the addition of naloxone did not confer substantial benefit over lofexidine monotherapy, although area-under-the-curve analysis showed that withdrawal severity in the naloxone/lofexidine combination group was significantly less than in the lofexidine monotherapy group, who experienced more severe withdrawal symptoms on days 4, 7, 9 and 13 of treatment. There were no significant differences in rates of completion of detoxification. Blood pressure remained within normal limits in both groups. Naltrexone maintenance treatment acceptability was low; only four patients continued with treatment for 5 or more days. The modest benefit of adding naloxone to lofexidine compared to the findings of previous opiate antagonist detoxification treatment studies is discussed in the context of the hypothesis that a critical level of opiate receptor occupancy is required to accelerate resolution of opiate withdrawal; the neurochemical mechanisms which may promote this are discussed.", "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.", "This study compares a naltrexone/lofexidine combination treatment with a 7-day course of lofexidine alone in the treatment of opiate withdrawal in 22 opiate-dependent patients. Withdrawal symptoms were significantly less severe on days 4-7, and 9-13, in the naltrexone/lofexidine combination group. There were no significant differences in the percentage of patients completing detoxification or in the mean length of stay for the two groups. Both treatments had similar, minimal effects on blood pressure. The naltrexone/lofexidine combination was associated with a more rapid resolution of the opiate withdrawal syndrome than a 7-day lofexidine-only treatment schedule, without substantial increases in withdrawal symptoms or hypotensive side-effects.", "This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NB group, 59% experienced clinically relevant withdrawal (defined as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance." ]

[ "11836309", "15760966", "17074344", "16439507", "15979994", "16556673", "16895629", "19200959", "19165664", "12970285" ]

[ "Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization.", "GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study.", "Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates.", "Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial.", "A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.", "GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study.", "Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study.", "1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study.", "Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.", "Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment." ]

[ "In a randomized multicenter study, the efficacies of two different GnRH agonists were compared with that of hCG for triggering final stages of oocyte maturation after ovarian hyperstimulation for in vitro fertilization. Ovarian stimulation was conducted by recombinant FSH (Puregon), and the GnRH antagonist ganirelix (Orgalutran) was coadministered for the prevention of a premature LH rise. Luteal support was provided by daily progestin administration. Frequent blood sampling was performed at midcycle in the first 47 eligible subjects included in the current study, who were randomized for a single dose of 0.2 mg triptorelin (n = 17), 0.5 mg leuprorelin (n = 15), or 10,000 IU hCG (n = 15). Serum concentrations of LH, FSH, E2, and progesterone (P) were assessed at variable intervals. LH peaked at 4 h after both triptorelin and leuprorelin administration, with median LH levels of 130 and 107 IU/liter (P < 0.001), respectively. LH levels returned to baseline after 24 h. Subjects receiving hCG showed peak levels of 240 IU/liter hCG 24 h after administration. A rise in FSH to 19 IU/liter (P < 0.001) was noted in both GnRH agonist groups 8 h after injection. Within 24 h the areas under the curve for LH and FSH were significantly higher (P < 0.001) in both GnRH agonist groups compared with that for hCG. E2 and P levels were similar for all groups up to the day of oocyte retrieval. Luteal phase areas under the curve for P and E2 were significantly elevated (P < 0.001) in the hCG group. The mean (+/-SD) numbers of oocytes retrieved were 9.8 +/- 5.4, 8.7 +/- 4.5, and 8.3 +/- 3.3; the percentages of metaphase II oocytes were 72%, 85%, and 86%; and fertilization rates were 61%, 62%, and 56% in the triptorelin, leuprorelin, and hCG group, respectively (P = NS for all three comparisons). These findings support the effective induction of final oocyte maturation in both GnRH agonist groups. In summary, after treatment with the GnRH antagonist ganirelix for the prevention of premature LH surges, triggering of final stages of oocyte maturation can be induced effectively by a single bolus injection of GnRH agonist, as demonstrated by the induced endogenous LH and FSH surge and the quality and fertilization rate of recovered oocytes. Moreover, corpus luteum formation is induced by GnRH agonists with luteal phase steroid levels closer to the physiological range compared with hCG. This more physiological approach for inducing oocyte maturation may represent a successful and safer alternative for in vitro fertilization patients undergoing ovarian hyperstimulation.", "We aimed to determine the efficacy of ovarian hyperstimulation protocols employing a GnRH antagonist to prevent a premature LH rise allowing final oocyte maturation and ovulation to be induced by a single bolus of either a GnRH agonist or hCG.\n A total of 122 normogonadotrophic patients following a flexible antagonist protocol was stimulated with recombinant human FSH and prospectively randomized (sealed envelopes) to ovulation induction with a single bolus of either 0.5 mg buserelin s.c. (n = 55) or 10,000 IU of hCG (n = 67). A maximum of two embryos was transferred. Luteal support consisted of micronized progesterone vaginally, 90 mg a day, and estradiol, 4 mg a day per os.\n Ovulation was induced with GnRH agonist in 55 patients and hCG in 67 patients. Significantly more metaphase II (MII) oocytes were retrieved in the GnRH agonist group (P < 0.02). Significantly higher levels of LH and FSH (P < 0.001) and significantly lower levels of progesterone and estradiol (P < 0.001) were seen in the GnRH agonist group during the luteal phase. The implantation rate, 33/97 versus 3/89 (P < 0.001), clinical pregnancy rate, 36 versus 6% (P = 0.002), and rate of early pregnancy loss, 4% versus 79% (P = 0.005), were significantly in favour of hCG.\n Ovulation induction with a GnRH agonist resulted in significantly more MII oocytes. However, a significantly lower implantation rate and clinical pregnancy rate in addition to a significantly higher rate of early pregnancy loss was seen in the GnRH agonist group, most probably due to a luteal phase deficiency.", "To evaluate the implant capacity of embryos derived from oocytes matured with a bolus of GnRH agonist.\n Donors were randomly assigned to a protocol using either GnRH agonist or recombinant (r) hCG to trigger ovulation. Analysis of variance, Student t test, and Fisher exact test were used where appropriate.\n Private clinical setting.\n Young voluntary donors receiving GnRH agonist (n = 30) or rhCG (n = 30). Eighty-nine patients received oocytes.\n Controlled ovarian stimulation was carried out with GnRH antagonist and FSH/LH in a step-down protocol. Donors received a single bolus of GnRH agonist (0.2 mg) or rhCG (250 microg). The endometrial tissue of recipient patients was prepared with oral E(2) and P.\n Pregnancy and implantation rates and ovarian hyperstimulation syndrome (OHSS) in an IVF donor program.\n No significant differences in the number of retrieved oocytes (327 vs. 288), MII oocytes (70% vs. 76%), fertilization (80% vs. 65%,), pregnancy/transfer (55% vs. 59%), and implantation rates (29% vs. 32%) were found between recipients whose embryos originated from donors in whom final oocyte maturation was triggered with GnRH agonist and those whose donors received hCG. Significant differences in luteal phase length (4.16 + 0.70 days vs. 13.63 + 2.12 days) and in OHSS (0/30 vs. 5/30) were seen between donors ovulated with the agonist and the donors in whom ovulation was triggered with hCG.\n In controlled ovarian stimulation IVF donor cycles, GnRH agonists trigger ovulation and induce luteolysis but do not compromise embryo implantation capacity.", "We aimed to examine the serum levels of inhibin A, vascular endothelial growth factor (VEGF), tumour necrosis factor alpha (TNFalpha), estradiol (E2) and progesterone levels after triggering of final oocyte maturation with GnRH agonist compared with HCG in patients with polycystic ovaries (PCO) and to investigate the relationship between these markers and ovarian hyperstimulation syndrome (OHSS).\n Twenty-eight patients with PCO, undergoing controlled ovarian hyperstimulation with FSH and GnRH antagonist for IVF-embryo transfer treatment, were randomized for triggering of final oocyte maturation with GnRH agonist (GnRH agonist group, n = 15) or HCG (HCG group, n = 13). Blood samples were obtained on the day of randomization and thereafter every 2-7 days. Serum levels of inhibin A, VEGF, TNFalpha, E2 and progesterone, the incidence of OHSS, ovarian size and pelvic fluid accumulation were evaluated.\n Serum inhibin A, E2 and progesterone levels were significantly lower in the GnRH agonist group compared with the HCG group, particularly on the day of embryo transfer (P < 0.0001). Serum VEGF and TNFalpha levels were similar between the two groups. Four patients in the HCG group developed severe OHSS, whereas no patient had any symptoms or signs of OHSS in the GnRH-agonist group (P < 0.05).\n In patients with PCO treated with FSH/GnRH antagonist, final oocyte maturation with GnRH agonist instead of HCG reduces significantly inhibin A, E2 and progesterone levels during the luteal phase. This phenomenon reflects the inhibition of the corpus luteum function and may explain, at least in part, the mechanism of OHSS prevention in high-risk patients. Our results do not support a crucial role for VEGF or TNFalpha in OHSS.", "Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed.\n 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established.\n No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52).\n Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.", "The aim of the study was to investigate whether intranasal (IN) administration of a GnRH agonist could provide luteal support in IVF/ICSI patients.\n Controlled ovarian hyperstimulation (COH) was performed using hMG/FSH and a GnRH antagonist. Patients were then randomly allocated to either 10,000 IU hCG, followed by vaginal administration of micronized progesterone (3x 200 mg/day) (group A), or 200 microg IN buserelin followed by either 100 microg every 2 days (group B), or 100 microg every day (group C), or 100 microg twice a day (group D), or 100 microg three times a day (group E). Luteal support was continued for 15 days.\n Twenty-three patients were randomized. Groups B and C were discontinued prematurely in view of the short luteal phase. The luteal phase was significantly shorter in groups B, C and D, whereas group E was comparable with group A, 13.5 and 13.0 days, respectively. In the mid-luteal phase, median progesterone levels were significantly lower in groups B, C and D, whereas group E was comparable with group A, 68.9 and 98.0 ng/ml, respectively. Estradiol (E2) was significantly reduced in groups B and D but sustained in group E. In the hCG group, LH levels were undetectable (<0.1 IU/l), whereas LH was detectable and significantly higher in groups C, D and E. Two pregnancies were obtained in the hCG group (two of five), one ectopic and one ongoing. Three pregnancies were obtained in group E, one miscarriage and two ongoing twin pregnancies (three of five).\n IN administration of buserelin may be effective in triggering follicular maturation and providing luteal phase support in patients undergoing assisted reproduction techniques (ART).", "Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to determine the clinical and endocrine effects as well the optimal timing of HCG supplementation. Forty-five normogonadotrophic IVF/ICSI patients following a flexible antagonist protocol were prospectively randomized (sealed envelopes) to triggering of ovulation with a single bolus of either 10,000 IU of HCG (group 1, n = 15) or 0.5 mg buserelin s.c. In addition, the GnRHa triggered group was randomized into two groups: group 2 (n = 17) was supplemented with HCG 1500 IU, 12 h after ovulation induction and group 3 (n = 13) was supplemented with HCG 1500 IU 35 h after ovulation induction. Group 1 and group 3 had significantly higher luteal phase concentrations of progesterone (P < 0.001) as compared with group 2. Moreover, the clinical pregnancy rate of groups 1 and 3 was similar and significantly higher (P < 0.02) than that of group 2. A larger study, however, is required to substantiate these differences. No differences were seen regarding mid-luteal inhibin A concentrations between the three groups. Triggering of ovulation with GnRHa supplemented with 1500 IU HCG 35 h later (group 3) seems to secure a normal luteal phase and a normal clinical pregnancy outcome.", "To prospectively assess the reproductive outcome with a small bolus of hCG administered on the day of oocyte retrieval after ovulation induction with a GnRH agonist (GnRHa).\n Prospective, randomized trial.\n Three hospital-based IVF clinics.\n Three hundred five IVF/intracytoplasmic sperm injection patients after a GnRH antagonist protocol.\n Ovulation induction was performed with either 10,000 IU hCG or 0.5 mg GnRHa (buserelin) supplemented with 1,500 IU hCG on the day of oocyte retrieval.\n Reproductive outcome in the two groups.\n No significant differences were seen regarding positive hCG/ET rate (48% and 48%), ongoing pregnancy rate (26% and 33%), delivery rate (24% and 31%), and rate of early pregnancy loss (21% and 17%) between the GnRHa and 10,000 IU hCG groups, respectively.\n A small bolus of hCG in the GnRHa group secured the luteal phase, resulting in a comparable reproductive outcome in the two groups. However, a nonsignificant difference of 7% in delivery rates justifies further studies to refine the use of GnRHa for ovulation induction.\n Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "To compare donor and recipient outcome after inducing the final oocyte maturation with hCG or GnRH agonist in GnRH-antagonist treated oocyte donation (OD) cycles.\n Two-hundred fifty-seven oocyte donors were enrolled to participate in a clinical trial in a private fertility centre. After stimulation with 225 IU rFSH and Cetrorelix 0.25 mg/day, 212 oocyte donors were randomised with sealed envelopes for triggering with recombinant hCG (Ovitrelle 250 microgr, n = 106) or a GnRH agonist (triptorelin 0.2 mg, n = 106).\n The number of retrieved COCs (12 +/- 6.3 vs 11.4 +/- 6.4), mature oocytes (8 +/- 4.6 vs 7.5 +/- 4.1), the proportion of mature oocytes (67.2 +/- 20.4% vs 67.1 +/- 20.9%) and fertilisation rates (67.8 +/- 23.5% vs 71.1 +/- 22.1%) were comparable. Clinical, ongoing pregnancy and live birth rates were not statistically different in the corresponding recipient groups. Nine cases of mild and one case of severe OHSS occurred in hCG group, whereas no cases were detected in GnRH agonist group.\n The findings of our RCT suggest that donor and recipient outcome are comparable in OD cycles triggered with hCG or a GnRH agonist. Furthermore, the risk of OHSS seems to be reduced considerably, therefore the combination of a GnRH antagonist protocol with GnRH agonist triggering constitutes a safe treatment option for egg-donors.", "Replacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because of the known rapid recovery of pituitary function after antagonist cessation. This randomized two-center study was performed to compare nonsupplemented luteal phase characteristics after three different strategies for inducing final oocyte maturation. Forty patients underwent ovarian stimulation using recombinant (r-)FSH (150 IU/d, fixed) combined with a GnRH antagonist (antide; 1 mg/d) during the late follicular phase. When at least one follicle above 18 mm was observed, patients were randomized to induce oocyte maturation by a single injection of either r-human (h)CG (250 microg) (n = 11), r-LH (1 mg) (n = 13), or GnRH agonist (triptorelin; 0.2 mg) (n = 15). Retrieved oocytes were fertilized by either IVF or intracytoplasmatic sperm injection, depending on sperm quality. Embryo transfer was performed 3-4 d after oocyte retrieval. No luteal support was provided. Serum concentrations of FSH, LH, estradiol (E(2)), progesterone (P), and hCG were assessed at fixed intervals during the follicular and luteal phase. The median duration of the luteal phase was 13, 10, and 9 d for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.005). The median area under the curve per day (from 4 d post randomization until the onset of menses) for LH was 0.50, 2.34, and 1.07 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.001). The median area under the curve per day for P was 269 vs. 41 and 16 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P < 0.001). Low pregnancy rates (overall, 7.5%; range, 0-18% per started cycle) were observed in all groups. In conclusion, the nonsupplemented luteal phase was insufficient in all three groups. In the patients receiving r-hCG, the luteal phase was less disturbed, compared with both other groups, presumably because of prolonged clearance of hCG from the circulation and the resulting extended support of the corpus luteum. Despite high P and E(2) concentrations during the early luteal phase in all three groups, luteolysis started prematurely, presumably because of excessive negative steroid feedback resulting in suppressed pituitary LH release. Hence, support of corpus luteum function remains mandatory after ovarian stimulation for IVF with GnRH antagonist cotreatment." ]

[ "15808033" ]

[ "Managing nocturnal leg cramps--calf-stretching exercises and cessation of quinine treatment: a factorial randomised controlled trial." ]

[ "Quinine is a common treatment for nocturnal leg cramps but has potential side effects. An uncontrolled study suggested that calf-stretching exercises could prevent nocturnal leg cramps (night cramps) but these findings have never been confirmed.\n To assess the effect of calf-stretching exercises and cessation of quinine treatment for patients with night cramps taking quinine.\n Randomised controlled trial.\n Twenty-eight general practices in southern England.\n One hundred and ninety-one patients prescribed quinine for night cramps were randomised to one of four groups defined by two \"advice\" factors: undertake exercises and stop quinine. After 6 weeks they were advised that they could take quinine and undertake the exercises freely. Documentation of cramp at 12 weeks was achieved in 181 (95%) patients. Main outcome measures were: symptom burden score, and frequency of night cramps and quinine usage.\n At 12 weeks there was no significant difference in number of cramps in the previous 4 weeks (exercise = 1.95, 95% confidence interval [CI] = -3.01 to 6.90; quinine cessation = 3.45, 95% CI = -1.52 to 8.41) nor symptom burden or severity of cramps. However, after 12 weeks 26.5% (95% CI = 13.3% to 39.7%) more patients who had been advised to stop quinine treatment reported taking no quinine tablets in the previous week (odds ratio [OR] = 3.32, 95% CI = 1.37 to 8.06), whereas advice to do stretching exercises had no effect (OR = 0.73, 95% CI = 0.27 to 1.98).\n Calf-stretching exercises are not effective in reducing the frequency or severity of night cramps. Advising those on long-term repeat prescriptions to try stopping quinine temporarily will result in no major problems for patients, and allow a significant number to stop medication." ]

[ "812666" ]

[ "A double-blind comparative study of the analgesic effects of fenbufen, codeine, aspirin, propoxyphene and placebo." ]

[ "nan" ]

[ "14586625", "11579852", "3875776" ]

[ "Should hyperbaric oxygen be added to treatment in idiopathic sudden sensorineural hearing loss?", "Sudden hypoacusis treated with hyperbaric oxygen therapy: a controlled study.", "[Hyperbaric oxygen therapy in sudden deafness]." ]

[ "At present, there is still no agreement about the therapy of idiopathic sudden sensorineural hearing loss (ISSHL). Hyperbaric oxygen (HBO) is used in the therapy of ISSHL to increase the partial oxygen pressure and the oxygen concentration in the inner ear and also to improve the blood profile and the microcirculation. In our prospective randomized study, we aimed to investigate the therapeutic effects of HBO therapy in the 1st 2 weeks of the onset of ISSHL. Fifty-one hospitalized patients with confirmed ISSHL who had received therapy were grouped randomly into two groups. Twenty-one patients (group I) received steroids, plasma expander dextrans (rheomacrodex), diazepam, pentoxiphylline and salt restriction, and 30 patients (group II) received the same basic treatment with the addition of HBO therapy. Audiological assessments of the patients were performed before and after the treatment. The hearing gains at frequencies of 250, 500, 1,000, 2,000 and 4,000 Hz were calculated separately. The level of hearing loss at the five frequencies was assessed in three groups at the first visit: equal or below 60 dB, between 61-80 dB and equal or above 81 dB. The average of the mean hearing gains at the five frequencies of the patients according to the age groups in group II was compared. The mean hearing gains at the five frequencies were compared between the two groups, and statistically significant improvement was detected in all the frequencies except at 2,000 Hz in group II. The mean hearing gains in group II were found to be significantly high in patients with initial hearing levels up to 60 dB in comparison to patients with initial hearing levels below 60 dB. When age groups and mean hearing gains were compared, there was no statistically significant difference in group I. In group II, the mean hearing gains were 39.1+/-18.3 dB in patients younger than 50 years and 22.7+/-11.3 dB in patients older than 50 years ( P=0.044). In conclusion, the addition of HBO therapy to conventional treatment modalities significantly improves the outcome of ISSHL, especially at the frequencies of 250, 500, 1,000 and 4,000 Hz and in hearing loss of above 61 dB. Furthermore, HBO therapy was found to be more effective in patients younger than 50 years.", "The term sudden hypoacusis describes a hearing loss of rapid onset and unknown origin that can progress to severe deafness. Of the many therapeutic protocols that have been proposed for treating sudden hypoacusis, hyperbaric oxygen therapy (HOT) plays a leading role. We studied 50 patients who had been referred to our ENT unit within 48 hours of the onset of sudden hypoacusis. We randomly assigned 30 of these patients to undergo once-daily administration of HOT for 10 days; the other 20 patients were treated for 10 days with an intravenous vasodilator. Response to therapy in all patients was evaluated by calculating the mean hearing threshold at frequencies between 500 and 4,000 Hz and by assessing liminal tonal audiometry results recorded at baseline and 10 days after the cessation of treatment. These results, plus the findings of other audiologic and otoneurologic examinations, revealed that the patients in the HOT group experienced a significantly greater response to treatment than did those in the vasodilator group, regardless of age and sex variables. Significantly more patients in the HOT group experienced a good or significant response. In both groups, patients with pantonal hypoacusis responded significantly better than did those with a milder condition. Based on our findings, coupled with the fact that oxygen therapy is well tolerated and produces no side effects, we conclude that HOT should be considered the preferred treatment for patients with sudden hypoacusis.", "Based on two independent studies, an attempt is made in this paper to demonstrate the effect of hyperbaric oxygen therapy used as a supportive measure to accompany standard treatment in recent acute loss of hearing and in acute loss of hearing where preoperative treatment has proved unsatisfactory. Whereas hyperbaric oxygen therapy is superior to the standard treatment alone as far as the cochlear perception dysacousis and tinnitus in recent acute loss of hearing are concerned, these results could not be reproduced in existing, preoperatively treated acute loss of hearing. As such, hyperbaric oxygen therapy under the strict supervision of a specialist physician has proved an effective supportive measure in the treatment of recent acute loss of hearing." ]

[ "4914579", "18378519", "6794796", "7012398", "1682683", "3624815", "14654762", "7944835", "1764497" ]

[ "Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg.", "Treatment of hypertension in patients 80 years of age or older.", "Blood pressure reduction in elderly: a randomised controlled trial of methyldopa.", "Prospective study on the treatment of mild hypertension in the aged.", "Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension)", "Compliance to treatment for hypertension in elderly patients: the SHEP pilot study. Systolic Hypertension in the Elderly Program.", "Results of the pilot study for the Hypertension in the Very Elderly Trial.", "Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program.", "Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization." ]

[ "nan", "Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.\n We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.\n The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).\n The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.", "A total of 123 out of 549 elderly residents of local authority welfare homes in Nottinghamshire were found at screening to have a standing or lying diastolic blood pressure of 100 mm Hg or more. These 123 subjects were randomly allocated to simple observation or to treatment with methyldopa. The cumulative mortality was similar in the observed and treated groups and in the normotensive group from which the subjects had been separated. Thus moderate hypertension, whether treated or not, was not a major risk predictor in the elderly population studied.", "The 4 year prospective trial on the effectiveness of the antihypertensive treatment was performed in 100 mild hypertensive patients of the aged, the average age being 76.1 years. Dropouts during the drug-off control period were 9 cases. The matched pair group was selected by the age, sex, and blood pressure. Forty-four drug treated cases and 47 placebo treated cases were comparable in blood pressure as well as in laboratory data. Cerebrovascular and cardiac complications were observed in 4 cases or 10.5% in the drug group, and in 9 cases or 22.0% in the placebo group. When 8 cases of blood pressure elevation over 200/110 mmHg in the placebo group were added to the cardiovascular complications, dropouts in placebo group reached 41.5%, and this showed the significant difference. Other complications were observed in 12 cases or 31.6% in the drug group and in 17 cases or 41.5% in the placebo group. Major complications were cancers, infections, and bone or joint diseases. Blood pressure was decreased from 171/87 to 151/80 in the drug group, and the average decrease was 20/7 mmHg in 4 year period. No significant changes in hematocrit, serum protein, urea nitrogen, uric acid, sodium, and potassium were observed during the trial period. The present study suggested that antihypertensive treatment was effective in the aged with mild hypertension, and that careful follow up was needed not only for cardiovascular complications but also for general health condition.", "Although the benefits of antihypertensive treatment in \"young\" elderly (under 70 years) hypertensive patients are well established, the value of treatment in older patients (70-84 years) is less clear. The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomised, double-blind, intervention study set up to compare the effects of active antihypertensive therapy (three beta-blockers and one diuretic) and placebo on the frequency of fatal and non-fatal stroke and myocardial infarction and other cardiovascular death in hypertensive Swedish men and women aged 70-84 years. We recruited 1627 patients at 116 health centres throughout Sweden, who were willing to participate, and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg, or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure. The total duration of the study was 65 months and the average time in the study was 25 months. 812 patients were randomly allocated active treatment and 815 placebo. The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint, death, or study termination was 19.5/8.1 mm Hg. Compared with placebo, active treatment significantly reduced the number of primary endpoints (94 vs 58; p = 0.0031) and stroke morbidity and mortality (53 vs 29; p = 0.0081). Although we did not set out to study an effect on total mortality, we also noted a significantly reduced number of deaths in the active treatment group (63 vs 36; p = 0.0079). The benefits of treatment were discernible up to age 84 years. We conclude that antihypertensive treatment in hypertensive men and women aged 70-84 confers highly significant and clinically relevant reductions in cardiovascular morbidity and mortality as well as in total mortality.", "Assessing the compliance of people over 60 years of age and older with an antihypertensive treatment regimen was a major objective of the Systolic Hypertension in the Elderly Program (SHEP) pilot study. The study randomized 551 men and women over the age of 60 (mean age = 72 years) to a stepped care treatment that included chlorthalidone or placebo in a double-blind trial. Three measures of compliance to treatment protocol--pill count, self-report, and a urine chlorthalidone assay--all indicated high levels of compliance in 80 to 90% of participants at 3 months and 1 year after randomization. Pill-taking compliance was similar in the active and placebo groups, although the rate of discontinuance from study medications at 1 year was higher in the placebo than in the active group. Compliance was high in all age categories, including those over age 80. These data suggest that elderly patients can achieve high levels of compliance with antihypertensive medications.", "The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality.\n To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues.\n The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months.\n In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01).\n The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.", "Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities.\n A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447,921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed.\n Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period.\n The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities.", "The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. This article describes the objectives and the protocol of Syst-Eur, a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups. A one-year pilot trial (1989) showed that the protocol is practicable. The Ethics Committee therefore decided to start the definite study (1990), in which randomized patients will be followed for 5 years. Recruitment of new centres and of the required 3,000 patients will last 3 years (until 1993)." ]

[ "11451839", "17356094" ]

[ "Efficacy of recombinant human deoxyribonuclease I in the hospital management of respiratory syncytial virus bronchiolitis.", "Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis." ]

[ "To evaluate the effect of recombinant human deoxyribonuclease I (rhDNase) in shortening the length of the hospitalization and improving the chest radiographs (CXRs) in hospitalized infants with respiratory syncytial virus (RSV) infection as a result of its mucolytic properties.\n Randomized, double-blind, placebo-controlled investigation of 75 patients with RSV bronchiolitis. The study was conducted at the University of Michigan Medical Center and St. Joseph Mercy Hospital, both in Ann Arbor, MI.\n The respiratory rate, wheezing, and retraction difference scores, obtained by subtracting the hospital discharge score from the corresponding hospital admission score, show no difference between the two groups, but the CXR difference scores show that the rhDNase group improved by 0.46 while the placebo group worsened by 0.60 (p < 0.001). Analysis of covariance for the hospital discharge CXR score after adjusting for the hospital admission score for both groups was done. There was a difference in scores between the two groups, with adjusted mean for the study group of 2.03, and 2.76 for the placebo group (p < 0.001). Paired t test statistics in each of the two groups were computed. For the placebo group, the mean increase of 0.60 was significant (p = 0.02), and the mean decrease of 0.46 for the rhDNase group was also significant (p = 0.02). A one-way analysis of covariance with the hospital discharge CXR scores as the dependent variable and the hospital admission score as the covariate showed that there was a significant difference between the groups (p = 0.01).\n In patients with RSV bronchiolitis, there was significant improvement in the CXRs with the use of rhDNase compared to significant worsening in the placebo group. To our knowledge, this is the first report of the use of rhDNase to treat RSV bronchiolitis.", "Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase).\n In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions.\n There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95% confidence interval, 0.96 to 1.33); for the duration of supplemental oxygen, the ratio was 1.28 (95% confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions.\n Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis." ]

[ "15572276", "12562742", "9617509", "15169694", "12091192" ]

[ "Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol.", "Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial.", "Risperidone compared with both lithium and haloperidol in mania: a double-blind randomized controlled trial.", "Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial.", "Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety." ]

[ "In a randomized, double-blind trial, patients with acute bipolar mania received 1-6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks, followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients, 154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal disorder and hyperkinesias, the most commonly reported adverse events with antipsychotic use, occurred less frequently with risperidone than haloperidol. We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term.", "Few double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic in acute mania.\n To determine the efficacy of risperidone in combination with a mood stabiliser in acute mania.\n Patients taking a mood stabiliser were randomised to 3 weeks' treatment with risperidone (n=75) or placebo (n=76).\n Young Mania Rating Scale (YMRS) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group. At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups, respectively. Significant improvements v. placebo (P<0.05) were noted in the risperidone group on several other clinically meaningful measures. Additionally, a post hoc analysis excluding carbamazepine-treated patients (plasma concentrations of risperidone active moiety were 40% lower in this group) revealed significantly greater reductions (P=0.047) in YMRS scores in the risperidone group than in the placebo group. Incidence of adverse events was similar in both groups.\n Risperidone is superior to placebo when used in combination with lithium or divalproex in acute mania.", "Case reports and studies of other neuroleptics suggest the efficacy of risperidone in the treatment of mania. Forty-five inpatients with DSM-IV mania were studied in a 28-day randomized, controlled, double-blind trial of either 6 mg daily of risperidone, 10 mg daily of haloperidol, or 800 to 1200 mg daily of lithium. The patients in all three groups showed a similar improvement on the total score for all rating scales at day 28 (Brief Psychiatric rating scale; lithium 9.1, haloperidol 4.9, risperidone 6.5, F = 1.01, df = 2, p = 0.37; Mania rating scale; lithium 15.7, haloperidol 10.2, risperidone 12.4, F = 1.07, df = 2, p = 0.35 [analysis of variance]). The Global Assessment of Functioning and Clinical Global Impression data showed a similar pattern of improvement. This study suggests that risperidone is of equivalent efficacy to lithium and haloperidol in the management of acute mania. The extrapyramidal side effects of risperidone and haloperidol were not significantly different.", "This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania.\n Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score >/==\" BORDER=\"0\">20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1-6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale.\n Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low.\n Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study.", "The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania.\n This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures.\n The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively.\n Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated." ]

[ "11368733", "10712354", "10492263", "10653047", "9358137" ]

[ "Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial.", "A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma.", "Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.", "Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics.", "Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group." ]

[ "Inhaled long-acting beta(2)-agonists improve asthma control when added to inhaled corticosteroid (ICS) therapy.\n To determine whether ICS therapy can be reduced or eliminated in patients with persistent asthma after adding a long-acting beta(2)-agonist to their treatment regimen.\n A 24-week randomized, controlled, blinded, double-dummy, parallel-group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 through January 1999.\n One hundred seventy-five patients aged 12 through 65 years with persistent asthma that was suboptimally controlled during a 6-week run-in period of treatment with inhaled triamcinolone acetonide (400 microg twice per day).\n Patients continued triamcinolone therapy and were randomly assigned to receive add-on therapy with either placebo (placebo-minus group, n = 21) or salmeterol xinafoate, 42 microg twice per day (n = 154) for 2 weeks. The entire placebo-minus group was assigned and half of the salmeterol group (salmeterol-minus group) was randomly assigned to reduce by 50% (for 8 weeks) then eliminate (for 8 weeks) triamcinolone treatment. The other half of the salmeterol group (salmeterol-plus group) was randomly assigned to continue both salmeterol and triamcinolone for the remaining 16 weeks (active control group).\n Time to asthma treatment failure in patients receiving salmeterol.\n Treatment failure occurred in 8.3% (95% confidence interval [CI], 2%-15%) of the salmeterol-minus group 8 weeks after triamcinolone treatment was reduced compared with 2.8% (95% CI, 0%-7%) of the salmeterol-plus group during the same period. Treatment failure occurred in 46.3% (95% CI, 34%-59%) of the salmeterol-minus group 8 weeks after triamcinolone therapy was eliminated compared with 13.7% (95% CI, 5%-22%) of the salmeterol-plus group. The relative risk (95% CI) of treatment failure at the end of the triamcinolone elimination phase in the salmeterol-minus group was 4.3 (2.0-9.2) compared with the salmeterol-plus group (P<.001).\n Our results indicate that in patients with persistent asthma suboptimally controlled by triamcinolone therapy alone but whose asthma symptoms improve after addition of salmeterol, a substantial reduction (50%) in triamcinolone dose can occur without a significant loss of asthma control. However, total elimination of triamcinolone therapy results in a significant deterioration in asthma control and, therefore, cannot be recommended.", "Adding inhaled long-acting beta(2)-agonists to a low dose of inhaled corticosteroids (ICS), results in better clinical asthma control than increasing the dose of ICS. However, this approach may mask underlying airway inflammation. In a double-blind parallel-group study, we evaluated the effect of adding formoterol to a low dose of budesonide, compared with a higher dose of budesonide, on the composition of induced sputum. After a 4-wk run-in period of treatment with budesonide (800 microg, twice daily), 60 patients with moderate asthma were randomly assigned to a 1-yr treatment with 400 microg of budesonide plus placebo, twice daily (BUD800), or 100 microg of budesonide plus 12 microg of formoterol, twice daily (BUD200+F). All drugs were administered via Turbuhaler. Budesonide (800 microg, twice daily) during run-in significantly reduced median sputum eosinophils from 4.5 to 0.68%. No significant changes in the proportion of eosinophils, EG2(+) cells, other inflammatory cells, or ECP levels in sputum were observed over the ensuing 1-yr treatment with BUD200+F or BUD800. Clinical asthma control was not significantly different between both groups. In conclusion, no significant differences in sputum markers of airway inflammation were observed during a 1-yr treatment with a low dose of inhaled budesonide plus formoterol compared with a higher dose of budesonide.", "To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL).\n Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial.\n Allergy/respiratory care clinics.\n Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids.\n FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid.\n Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid.\n In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.", "Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.", "The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.\n After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.\n The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.\n In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma." ]

[ "831502", "6434973", "18694901", "6416059", "15210660", "15607839", "6829517", "3762845" ]

[ "Observation and treatment of neonatal narcotic withdrawal.", "An evaluation of neonatal abstinence treatment modalities.", "Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial.", "Neonatal methadone withdrawal. Effect of two treatment regimens.", "A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome.", "Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops.", "Opiate v CNS depressant therapy in neonatal drug abstinence syndrome.", "Neonatal abstinence syndrome, pharmacotherapy and developmental outcome." ]

[ "A total of 110 infants born to mothers who were either in a methadone maintenance program, using heroin, or recently detoxified, were studied during the neonatal period. Of these infants, 93.6 per cent developed withdrawal symptoms. No significant differences were determined in therapeutic response among those infants treated with methadone, phenobarbital, and diazepam. There was a significant reduction in the frequency of withdrawal symptoms among infants born to mothers whose methadone dose at time of delivery was less than 20 mg (17.9 per cent). It is suggested that reduction of methadone dosage in late pregnancy results in reduced incidence of withdrawal but must be carefully carried out.", "nan", "In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered.\n We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 mug/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system.\n Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated.\n Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.", "Thirty-one infants exposed to methadone in utero who required pharmacologic treatment for withdrawal symptoms were randomly assigned to a paregoric or phenobarbital treatment group. Seven infants had symptoms too mild to require treatment. Respiratory rate, blood pH, PCO2, systolic BP, and serum thyroxine concentrations were measured on the 4th, 7th, and 14th days of life. Platelet counts were performed on the seventh and 14th days of life, and urinary catecholamine excretion was measured on the sixth day of life. Rates of weight gain were recorded during the second and third weeks of life. With the exception of a slightly higher blood PCO2 level in the phenobarbital-treated infants on day 7, no significant intergroup differences were observed in the treated infants. Paregoric-treated infants required a significantly longer period of treatment than phenobarbital-treated infants (22 v 17 days). This may have been due, at least in part, to the prolonged half-life and relatively high blood levels of phenobarbital present after cessation of therapy.", "The incidence of neonatal abstinence syndrome (NAS) has increased 10-fold over the last decade in Glasgow. In the Princess Royal Maternity Hospital, it now accounts for 17% of special care baby unit (SCBU) admissions.\n To compare opiate replacement therapy (morphine sulphate) with the present standard treatment (phenobarbitone) for management of NAS. The primary study end point was duration of pharmaceutical treatment. Secondary end points were the requirement for additional drugs and the requirement for SCBU admission.\n Double blind, randomised controlled clinical trial.\n Differential diagnoses were excluded, and two consecutive Lipsitz scores > 4 defined NAS requiring treatment. Infants were randomised to receive morphine sulphate or phenobarbitone. Treatments were identical in appearance, odour, and volume. Increments, decrements, and discontinuation of treatments were protocol driven.\n Seventy five infants participated. All mothers received opiate replacement therapy (methadone) during pregnancy and most used other drugs (n = 62, 83%). No significant difference in maternal drug use patterns was observed between treatment groups. Median treatment duration was four days shorter with opiate replacement (8 v 12 days, Mann-Whitney U test, p = 0.02). Phenobarbitone treated infants tended to require second line treatment (47% v 35%, chi(2) test, p = 0.11) and SCBU admission (62% v 30%, chi(2) test, p = 0.04) more often.\n Opiate replacement therapy appears to be superior for management of symptomatic NAS when maternal opiate use is prevalent. The shorter treatment duration and lower requirement for higher intensity nursing may have significant cost implications. Tailoring NAS treatment to local maternal drug use may result in similar benefits.", "Treating opioid-addicted women with methadone in pregnancy increased the number of newborns suffering from neonatal abstinence syndrome (NAS). High-pitch crying, insomnia, tremor, myoclonic jerks, vomiting, diarrhoea and poor weight gain were reported symptoms, which were evaluated using the Finnegan (F)-score. Earlier phenobarbital or paregoric had been used to suppress symptoms. We surveyed the administration of pure mu-agonist morphine (MO) in comparison to the alcoholic opioid mixture in tincture of opium (TO). Thirty-three newborns were included in the survey, after informed consent by their parents.\n NAS started 3-5 days after delivery and lasted for 27 or 30 days (mean) in the TO and MO groups, respectively. In either of the tested parameters, we found no significant differences between the two groups (2P < 0.05). The maximum F-score was similar in both groups, but the dose to suppress NAS was higher in the MO group (0.6-0.5 mg/day; total dose 61.6-42.7 mg of morphine). The duration of the therapy was longer in the MO than in the TO group (37.5-32.4 days). On the other hand the weight gain was better in the MO group than in the TO group (25-19 g/day), but was reduced in both groups compared with healthy newborns.\n Morphine is suitable to treat NAS in a similar manner as tincture of opium, but avoids unwanted effects of the alcoholic extracts with various alkaloids in the tincture of opium and allows better weight gain of the newborns.", "Paregoric and phenobarbital, administered randomly in 153 passively addicted neonates, initially appeared to control neonatal abstinence signs equally well. However, seven of the 62 phenobarbital-treated newborns had abstinence-associated seizures within the first month of life, while none of 49 paregoric-treated neonates had seizures. Forty-two neonates initially requiring no specific pharmacotherapy for abstinence signs were born to mothers taking less methadone hydrochloride just before delivery. Five of those 42 neonates, however, had seizures within the first 14 days of life. Seizure occurrence could not be predicted from analysis of early abstinence patterns. We consider paregoric to be the treatment of choice for the neonatal abstinence syndrome. Phenobarbital use should be monitored with serum drug levels and modification of recommended dosage regimens considered.", "The majority of infants born to drug-dependent women undergo neonatal abstinence syndrome (NAS) and often require pharmacotherapy for the treatment of withdrawal symptoms. Phenobarbital, paregoric, and diazepam have been recommended for the treatment of the syndrome. While some investigators have examined the efficacy of these agents in treating NAS, there are no data regarding the use of specific pharmacologic agents and developmental outcome. This study evaluated 85 infants born to drug-dependent women who were maintained on methadone during pregnancy. Severity of infant withdrawal was assessed with the neonatal abstinence scoring system. Infants who required pharmacotherapy were randomly assigned to one of four treatment regimens: paragoric, phenobarbital (titration), phenobarbital (loading), and diazepam. When treatment was not successful with the assigned agent, one of the other agent(s) was used. At 6 months of age, the developmental status of infants was assessed with the Bayley Scales of Mental Development. Based on NAS treatment, four groups were defined: paregoric (n = 21); phenobarbital (n = 17); more than one agent (n = 31); and no treatment (n = 16). Data for the phenobarbital loading and titration groups were combined since analysis revealed no differences between groups. All infants who initially received diazepam were included in group III since diazepam as a single agent was not successful. Results of one way analysis of variance revealed no differences in developmental status between groups (p greater than 0.10, F = 0.25). Scores for all groups were well within the normal range of development.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "16503464", "21214940", "21304925", "19098989", "21159081", "21304923", "18611271" ]

[ "Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial.", "A trial of intermittent preventive treatment and home-based management of malaria in a rural area of The Gambia.", "Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial.", "Seasonal intermittent preventive treatment for the prevention of anaemia and malaria in Ghanaian children: a randomized, placebo controlled trial.", "The clinical impact of combining intermittent preventive treatment with home management of malaria in children aged below 5 years: cluster randomised trial.", "Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Mali: a randomised, double-blind, placebo-controlled trial.", "Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine targeting the transmission season on the incidence of clinical malaria in children in Mali." ]

[ "In the Sahel and sub-Sahelian regions of Africa, malaria transmission is highly seasonal. During a short period of high malaria transmission, mortality and morbidity are high in children under age 5 years. We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection.\n We did a randomised, placebo-controlled, double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar, a rural area of Senegal. 1136 children aged 2-59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season. The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection. Primary analysis was by intention-to-treat. This study is registered with , number NCT00132561.\n During 13 weeks of follow-up, the intervention led to an 86% (95% CI 80-90) reduction in the occurrence of clinical episodes of malaria. With passive case detection, protective efficacy against malaria was 86% (77-92), and when detected actively was 86% (78-91). The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk, whereas in those on placebo it was 2250 episodes per 1000 person-years at risk. 13 children were not included in the intention-to-treat analysis, which was restricted to children who received a first dose of antimalarial or placebo. There was an increase in vomiting in children who received the active drugs, but generally the intervention was well tolerated.\n Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection.", "Individual malaria interventions provide only partial protection in most epidemiological situations. Thus, there is a need to investigate whether combining interventions provides added benefit in reducing mortality and morbidity from malaria. The potential benefits of combining IPT in children (IPTc) with home management of malaria (HMM) was investigated.\n During the 2008 malaria transmission season, 1,277 children under five years of age resident in villages within the rural Farafenni demographic surveillance system (DSS) in North Bank Region, The Gambia were randomized to receive monthly IPTc with a single dose of sulphadoxine/pyrimethamine (SP) plus three doses of amodiaquine (AQ) or SP and AQ placebos given by village health workers (VHWs) on three occasions during the months of September, October and November, in a double-blind trial. Children in all study villages who developed an acute febrile illness suggestive of malaria were treated by VHWs who had been taught how to manage malaria with artemether-lumefantrine (Coartem™). The primary aims of the project were to determine whether IPTc added significant benefit to HMM and whether VHWs could effectively combine the delivery of both interventions.\n The incidence of clinical attacks of malaria was very low in both study groups. The incidence rate of malaria in children who received IPTc was 0.44 clinical attacks per 1,000 child months at risk while that for control children was 1.32 per 1,000 child months at risk, a protective efficacy of 66% (95% CI -23% to 96%; p = 0.35). The mean (standard deviation) haemoglobin concentration at the end of the malaria transmission season was similar in the two treatment groups: 10.2 (1.6) g/dL in the IPTc group compared to 10.3 (1.5) g/dL in the placebo group. Coverage with IPTc was high, with 94% of children receiving all three treatments during the study period.\n Due to the very low incidence of malaria, no firm conclusion can be drawn on the added benefit of IPTc in preventing clinical episodes of malaria among children who had access to HMM in The Gambia. However, the study showed that VHWs can successfully combine provision of HMM with provision of IPTc.", "Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN).\n An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥ 5,000/µl, was 2.88 (95% confidence interval [CI] 2.70-3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78-0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%-74%) (p<0.001). There was a 69% (95% CI 6%-90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%-69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%-77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%-70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65-1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72-0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3-3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded.\n IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission.\n ClinicalTrials.govNCT00738946. Please see later in the article for the Editors' Summary.", "Malaria and anaemia are the leading causes of morbidity and mortality in children in sub-Saharan Africa. We have investigated the effect of intermittent preventive treatment with sulphadoxine-pyrimethamine or artesunate plus amodiaquine on anaemia and malaria in children in an area of intense, prolonged, seasonal malaria transmission in Ghana.\n 2451 children aged 3-59 months from 30 villages were individually randomised to receive placebo or artesunate plus amodiaquine (AS+AQ) monthly or bimonthly, or sulphadoxine-pyrimethamine (SP) bimonthly over a period of six months. The primary outcome measures were episodes of anaemia (Hb<8.0 g/dl) or malaria detected through passive surveillance.\n Monthly artesunate plus amodiaquine reduced the incidence of malaria by 69% (95% CI: 63%, 74%) and anaemia by 45% (95% CI: 25%,60%), bimonthly sulphadoxine-pyrimethamine reduced the incidence of malaria by 24% (95% CI: 14%,33%) and anaemia by 30% (95% CI: 6%, 49%) and bimonthly artesunate plus amodiaquine reduced the incidence of malaria by 17% (95% CI: 6%, 27%) and anaemia by 32% (95% CI: 7%, 50%) compared to placebo. There were no statistically significant reductions in the episodes of all cause or malaria specific hospital admissions in any of the intervention groups compared to the placebo group. There was no significant increase in the incidence of clinical malaria in the post intervention period in children who were >1 year old when they received IPTc compared to the placebo group. However the incidence of malaria in the post intervention period was higher in children who were <1 year old when they received AS+AQ monthly compared to the placebo group.\n IPTc is safe and efficacious in reducing the burden of malaria in an area of Ghana with a prolonged, intense malaria transmission season.\n ClinicalTrials.gov NCT00119132.", "To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malaria-related morbidity in children <5 years of age who already had access to home-based management of malaria (HMM) for presumptive treatment of fevers.\n Thirty community-based drug distributors (CDDs) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunate-amodiaquine (AS+AQ) to all children under 5 years of age. Six communities were randomised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May, July and September of 2007. The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group. Cross-sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children.\n During the 6 months in which IPTc was delivered, incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone, but this difference was not statistically significant (protective efficacy: 37.0%(95% CI: -9.7 to 63.8; P = 0.14). However, incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis: protective efficacy 61.5% (95% CI:31.2-78.5; P = 0.018). Protection with IPTc was not followed by rebound morbidity in the following year. At the end of the intervention period, prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc, but there were no differences in anaemia or haemoglobin concentration.\n In this study area, incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM. However, high levels of coverage for IPTc will be necessary for maximum impact.\n © 2010 Blackwell Publishing Ltd.", "Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established.\n To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3-59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p = 0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76-2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29-0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%-85%) (p<0.001) on the primary endpoint. There were 15 episodes of severe malaria in children in the control arm compared to two in children in the intervention group giving a PE of 87% (95% CI 42%-99%) (p = 0.001). IPTc reduced the prevalence of malaria infection by 85% (95% CI 73%-92%) (p<0.001) during the intervention period and by 46% (95% CI 31%-68%) (p<0.001) at the end of the intervention period. The prevalence of moderate anaemia (haemoglobin [Hb] <8 g/dl) was reduced by 47% (95% CI 15%-67%) (p<0.007) at the end of intervention period. The frequencies of adverse events were similar between the two arms. There was no drug-related serious adverse event.\n IPTc given during the malaria transmission season provided substantial protection against clinical episodes of malaria, malaria infection, and anaemia in children using an LLIN. SP+AQ was safe and well tolerated. These findings indicate that IPTc could make a valuable contribution to malaria control in areas of seasonal malaria transmission alongside other interventions.\n ClinicalTrials.gov NCT00738946. Please see later in the article for the Editors' Summary.", "Recent studies have shown that intermittent preventive malaria treatment (IPT) in infants in areas of stable malaria transmission reduces malaria and severe anaemia incidence. However in most areas malaria morbidity and mortality remain high in older children.\n To evaluate the effect of seasonal IPT with sulphadoxine pyrimethamine (SP) on incidence of malaria disease in area of seasonal transmission, 262 children 6 months-10 years in Kambila, Mali were randomized to receive either IPT with SP twice at eight weeks interval or no IPT during the transmission season of 2002 and were followed up for 12 months. Subjects were also followed during the subsequent transmission season in 2003 to assess possible rebound effect. Clinical malaria cases were treated with SP and followed to assess the in vivo response during both periods.\n The incidence rate of malaria disease per 1,000 person-months during the first 12 months was 3.2 episodes in the treatment group vs. 5.8 episodes in the control group with age-adjusted Protective Efficacy (PE) of 42.5%; [95% CI 28.6%-53.8%]. When the first 16 weeks of follow up is considered age-adjusted PE was 67.5% [95% CI 55.3% - 76.6%]. During the subsequent transmission season, the incidence of clinical malaria per 1000 persons-days was similar between the two groups (23.0 vs 21.5 episodes, age-adjusted IRR = 1.07 [95% CI, 0.90-1.27]). No significant difference was detected in in vivo response between the groups during both periods.\n Two malaria intermittent treatments targeting the peak transmission season reduced the annual incidence rate of clinical malaria by 42.5% in an area with intense seasonal transmission. This simple strategy is likely to be one of the most effectives in reducing malaria burden in such areas.\n Clinicaltrials.gov NCT00623155." ]

[ "6695009", "517465", "8326055" ]

[ "Effects of physical conditioning on self-concept of adult obese males.", "Helping police officers to cope with stress: a cognitive--behavioral approach.", "Psychological and physical benefits of circuit weight training in law enforcement personnel." ]

[ "The purpose of the study was to investigate possible psychological changes in obese men after participating in an eight-week nutrition and physical conditioning program. The subjects, 45 male, metropolitan policemen who were considered at least 20 percent over their optimum body weights, were placed on diets and received weekly instruction on topics of nutrition and exercise. The subjects were randomly divided into two groups, one that participated in aerobic conditioning and one that did not. The amount of oxygen consumption, as an index of physical fitness, and performance on selected subscales of the Tennessee Self-concept Scale (TSCS) were measured before and after the training and conditioning programs. Both groups displayed significant increases in oxygen consumption and on the Physical Self and Self-satisfaction subscales, but on all these measures, the Conditioning Group increased significantly (2 to 3 times) more. For both groups, the Total Variability measure from the TSCS showed significant reductions, which have been associated with personality integration. These results demonstrate that physical conditioning and dietary educational sessions or educational sessions alone are associated with positive changes in self-concept in obese individuals and also corroborate other studies that show links between physical and psychological fitness.", "Police Academy trainees participated in a stress management program which focused on developing skills for coping with anxiety and anger. Stress management training took place in six 2-hour sessions and included instruction and practice in the self-monitoring of reactions to stressful situations, muscular relaxation, and the development of adaptive self-statements. Self-report measures of anxiety and anger were obtained before and after the stress management program. In addition, self and observer ratings of trainees' performance in stressful simulated police activities were utilized as posttreatment dependent measures. In comparison to a control group of trainees, the performance of the treatment group was rated, by academy personnel, as superior in several of the simulated police activities. The results of the present study suggest that stress management with law enforcement officers may be most effective when the program focuses on the specific situations which are likely to be encountered by trainees. Limitations of the present program are examined and suggestions for future efforts with law enforcement personnel are discussed.", "The effects of circuit weight training on mood, perceived stress, job satisfaction, and physical symptoms were investigated in a sample of state law enforcement officers. Forty-three male officers who were not regularly exercising were assigned to either 4 months of circuit weight training or a wait-list control condition. Four months of circuit weight training led to a significant increase in strength on cardiovascular fitness. Subjects also demonstrated significant improvements in mood, including decreases in somatization, anxiety, depression, and hostility. Circuit weight training also resulted in a decrease in reports of physical symptoms and in improvements in job satisfaction. Results indicated that subjects who dropped out of the exercise training program evidenced significantly greater anxiety, depression, and hostility at pretreatment than subjects who completed the program. These findings suggest that circuit weight training programs may contribute to important psychological benefits." ]

[ "3962941", "12732859", "9313829", "18305069" ]

[ "Partially ventilated endotracheal suction. Use in newborns with respiratory distress syndrome.", "Closed suctioning of intubated neonates maintains better physiologic stability: a randomized trial.", "Closed versus open endotracheal suctioning in preterm infants: effects on cerebral oxygenation and blood volume.", "Lung volume and cardiorespiratory changes during open and closed endotracheal suction in ventilated newborn infants." ]

[ "Ventilator adapters that permit endotracheal suction without disconnection from mechanical ventilation may overcome several of the theoretical contributors to the hypoxia and bradycardia associated with neonatal endotracheal suction. Such an adapter allows for partially ventilated endotracheal suction (PVETS) as opposed to traditional, nonventilated endotracheal suction. To test the clinical value of PVETS using an endhole adapter, changes in transcutaneous partial pressure of oxygen and heart rate were compared during paired PVETS and nonventilated endotracheal suction events on 32 occasions in 11 premature neonates with respiratory distress syndrome. Partially ventilated endotracheal suction was associated with a significant decrease in the incidence and severity of hypoxic events. Partially ventilated endotracheal suction, however, did not affect the incidence of bradycardic events; PVETS had a small but statistically significant effect on reducing the severity of bradycardia. No clear relationship between bradycardic and hypoxic events was evident.", "To evaluate the physiological variance in a closed (CS) vs an open suction (OS) protocol in intubated infants.\n Infants were stratified into three weight groups in a randomized crossover trial. Heart rate, respiratory rate, blood pressure, oxygen saturation, transcutaneous oxygen and carbon dioxide, and end-tidal carbon dioxide were recorded prior to suctioning, during suctioning, and recovery to baseline. Following the procedures, recovery time to baseline parameters was measured. Data were analyzed using repeated measures ANOVA.\n Overall, there was significantly less deviation from baseline physiological parameters with CS. Infants <1000 g had clinically significant decreases in heart rate with the OS method (-18% OS vs -6% CS; p=0.016). Recovery time in the OS group was twice that of the CS cohort (4 vs 2 minutes; p<0.001).\n CS maintains better physiologic stability in intubated infants.", "The aim of our study was to compare, using near-infrared spectroscopy (NIRS), the effects on cerebral intracellular oxygenation and cerebral blood volume (CBV) of closed endotracheal suctioning (CS), which permits continuous ventilation of the patient, with open endotracheal suctioning (OS), which requires disconnection from the ventilator. Eleven preterm infants were studied. Each patient underwent one CS, followed, after 60 min, by one OS, or vice versa, three times during the same day. Modifications in CBV and oxidized cytochrome oxidase (CytO2) were continuously detected by NIRS; arterial oxygen saturation (SaO2) heart rate (HR), transcutaneous carbon dioxide tension and mean arterial blood pressure were simultaneously recorded. Significant reductions in HR and SaO2 were observed following OS; the magnitude and duration of these negative effects of suctioning were significantly reduced with CS. In addition, the decrease in CBV was more pronounced than following CS. No changes in CytO2 concentration were seen.", "To compare change in lung volume (DeltaV(L)), using respiratory inductive plethysmography, time to recover pre-suction lung volume (t(rec)) and the cardiorespiratory disturbances associated with open suction (OS) and closed suction (CS) in ventilated infants.\n Randomised blinded crossover trial.\n Neonatal intensive care unit.\n Thirty neonates, 20 receiving synchronised intermittent mandatory ventilation (SIMV) and 10 high-frequency oscillatory ventilation (HFOV, four receiving muscle relaxant).\n OS and CS were performed, in random order, on each infant using a 6FG catheter at -19 kPa for 6 seconds and repeated after 1 minute.\n DeltaV(L), oxygen saturation (Spo(2)) and heart rate were continuously recorded from 2 minutes before until 5 minutes after suction. Lowest values were identified during the 60 seconds after suction.\n Variations in all measures were seen during CS and OS. During SIMV no differences were found between OS and CS for maximum DeltaV(L) or t(rec); mean (95% CI) difference of 3.5 ml/kg (-2.8 to 9.7) and 4 seconds (-5 to 13), respectively. During HFOV t(rec) was longer during OS by 13 seconds (0 to 27) but there was no difference in the maximum DeltaV(L) of 0.1 mV (-0.02 to 0.22). A small reduction in SpO(2) with CS in the SIMV group mean difference 6% (2.1 to 9.8) was the only significant difference in physiological measurements.\n Both OS and CS produced transient variable reductions in heart rate and Spo(2). During SIMV there was no difference between OS and CS in DeltaV(L) or t(rec). During HFOV there was no difference in DeltaV(L) but a slightly longer t(rec) after OS." ]

[ "11109156", "9747366", "3139019", "16965415", "788768", "3903779", "11590398", "16684435", "15927814", "14433742", "1619073", "12807340", "7698835", "1026547" ]

[ "The effect of antibacterial soap with 1.5% triclocarban on Staphylococcus aureus in patients with atopic dermatitis.", "Flucloxacillin in the treatment of atopic dermatitis.", "Staphylococcal colonization in atopic dermatitis and the effect of topical mupirocin therapy.", "Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial.", "Co-operative double-blind trial of an antibiotic/corticoid combination in impetiginized atopic dermatitis.", "Fusidic acid plus betamethasone in infected or potentially infected eczema.", "Effects of cefuroxime axetil on Staphylococcus aureus colonization and superantigen production in atopic dermatitis.", "Efficacy and safety of silver textile in the treatment of atopic dermatitis (AD).", "A novel method to control the balance of skin microflora Part 2. A study to assess the effect of a cream containing farnesol and xylitol on atopic dry skin.", "Analysis of the results obtained in the treatment of atopic dermatitis with corticosteroid and neomycin containing ointments.", "Topical corticosteroids and Staphylococcus aureus in atopic dermatitis.", "Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison.", "Modern topical glucocorticoids and anti-infectives for superinfected atopic eczema: do prednicarbate and didecyldimethylammoniumchloride form a rational combination?", "A comparative clinical evaluation of a new topical steroid 'halcinonide' and hydrocortisone in steroid-responsive dermatoses." ]

[ "This double-blind study determined whether daily bathing with an antibacterial soap would reduce the number of Staphylococcus aureus on the skin and result in clinical improvement of atopic dermatitis. For 9 weeks, 50 patients with moderately severe atopic dermatitis bathed daily with either an antimicrobial soap containing 1.5% triclocarban or the placebo soap. They also used a nonmedicated moisturizer and 0.025% triamcinolone acetonide cream as needed, but the availability of the corticosteroid cream was discontinued after 6 weeks. The antimicrobial soap regimen caused significantly greater improvement in the severity and extent of skin lesions than the placebo soap regimen, which correlated with reductions both in S aureus in patients with positive cultures at baseline and in total aerobic organisms. Outcome measures included reductions in S aureus, total aerobic organisms, and dermatologic assessments. Overall, daily bathing with an antibacterial soap was well tolerated, provided clinical improvement, and reduced levels of skin microorganisms.", "Although colonization of atopic dermatitis by Staphylococcus aureus is universal and bacterial infection is common, it is not known whether antibiotic therapy is helpful in eczematous children who do not have any signs suggestive of bacterial infection. Fifty children aged 1-16 years with atopic dermatitis took part in a randomized double-blind placebo-controlled study of 4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. The change in the mean of the log10 of the counts/cm2 of S. aureus after 4 weeks of treatment was significantly different for patients receiving treatment, compared with the change for those receiving the placebo (P = 0.008). However, the difference in the change at 14 days after stopping treatment was not significant (P = 0.32). Methicillin-resistant strains of S. aureus were cultured from five children during or after treatment. Flucloxacillin did not improve the symptoms or clinical appearance of atopic dermatitis and only temporarily changed skin colonization by S. aureus.", "Forty-nine patients with atopic dermatitis entered a double blind placebo controlled cross-over study of mupirocin, a new topical antistaphylococcal antibiotic. Forty-five patients were evaluable. Quantitative bacteriological assessment before treatment showed that heavy colonization of the skin with Staphylococcus aureus was present in nearly all patients even in the absence of overt infection. However, the bacterial count was significantly reduced by 2 weeks' treatment with topical mupirocin, but not by the placebo. Moreover, a significant reduction of clinical severity was also observed after treatment with mupirocin, which was maintained over the following 4 weeks, although recolonization occurred during this period, with bacterial counts rising to pre-treatment levels. Despite recolonization, clinical deterioration was not observed during the trial period. No serious side-effects were observed. Phage typing showed that 50% of patients carried more than one bacterial phage type. Recolonization in eight patients (17%) was with a 'new' strain that had not previously been isolated.", "Staphylococcus aureus has a peculiar ability to colonize the skin of patients with eczema and atopic dermatitis (AD), and is consistently found in eczematous skin lesions in these patients. A correlation between the severity of the eczema and colonization with S. aureus has been demonstrated, and it has been determined that bacterial colonization is an important factor aggravating skin lesions. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results.\n To investigate the colonizing features of S. aureus in the lesional and nonlesional skin of patients with eczema and AD in China and to compare the therapeutic effect of mupirocin plus hydrocortisone butyrate with vehicle ointment plus hydrocortisone butyrate.\n A multicentre, double-blind randomized trial was conducted. Eczema Area and Severity Index (EASI) scores were evaluated before the start of the trial and on the 7th, 14th and 28th day of treatment. Swabs for bacterial isolation were taken from lesional skin before the start of the trial and on the 7th, 14th and 28th day of treatment, and from nonlesional skin only before the start of the trial. A combination topical therapy with mupirocin plus hydrocortisone butyrate ointment was used in the experimental group, with vehicle ointment plus hydrocortisone butyrate ointment as a control.\n Of 327 patients enrolled in the study, 208 had eczema and 119 had AD. Bacteria were isolated from 70.2% of lesional and 32.7% of nonlesional skin samples from patients with eczema, of which S. aureus accounted for 47.3% and 27.9%, respectively. Bacteria were isolated from 74.8% of lesional and 34.5% of nonlesional skin samples from patients with AD, of which S. aureus accounted for 79.8% and 80.5%, respectively. The colonization density of S. aureus was markedly higher in lesional than in nonlesional skin, both in patients with eczema and with AD (P < 0.01, P < 0.05), and was positively correlated with lesion severity. Considering the EASI scores before and after treatment and the final effective rate, good therapeutic effects were obtained in both the combination experimental groups and the control groups (P < 0.01), and there were no differences in the global therapeutic effect between the two groups in patients with eczema and with AD (P > 0.05). However, in patients with eczema with a clinical score of > 8 or in patients with AD with a clinical score of > 7, the therapeutic effect in the experimental groups was superior to that in the control groups (P < 0.05) on the 7th day of treatment. There were no differences between the two groups on the 14th and 28th days of treatment (P > 0.05). Following the improvement of symptoms and signs of eczema and AD, the positive rates of bacteria and S. aureus were reduced on the 7th day of treatment.\n This study confirmed that lesional skin of patients with eczema and AD was more frequently colonized with S. aureus than was nonlesional skin. The more severe the eczema, the higher the colonization rate of S. aureus, and S. aureus was also more often present in lesional and nonlesional skin in patients with AD than in those with eczema. Staphylococcus aureus infection is related to the pathogenesis of eczema and AD. An antibiotic-corticosteroid combination and corticosteroid alone both gave good therapeutic effect in eczema and in AD, and both reduced colonization by S. aureus. Early combined topical therapy is beneficial to patients with moderate to severe eczema and AD, and it is unnecessary to use antibiotics at later stages of disease or in mild eczema or AD.", "This double-blind study of an antibiotic coritcosteroid combination, the antibiotic alone and the corticosteroid alone, compared their clinical and microbiological effect in infected atopic dermatitis. Combination therapy reduced the mean scores for infection, inflammation and overall severity to a greater extent than the antibiotic or corticosteroid alone. The clinical and microbiological date are discussed in terms of relevance to clinical use.", "Eighty-one patients with atopic dermatitis and contact dermatitis received a 1-week treatment with 0.1% betamethasone alone on one side and 0.1% betamethasone plus 2% fusidic acid on the other side. Clinically, the combination was marginally superior and in patient preference a significant difference in favour of the combination was recorded. Bacteriologically, the combination eliminated 67% of bacteria originally present in the skin lesions compared with 51% with steroid alone.", "nan", "Patients with atopic dermatitis (AD) have an increased tendency to develop bacterial skin infections. Colonization with Staphylococcus aureus is known to be a major trigger and might also play a pathophysiological role. Because of their antiseptic action, silver-coated textiles suppress S. aureus colonization and toxin formation, thus damping the inflammatory reaction.\n To evaluate the clinical effectiveness and safety of a special silver textile in the treatment of patients suffering from acute AD.\n In a randomized phase II monocenter parallel-group comparative study 30 patients were recruited (average age 25.5 years, min. 4 years, max. 70 years) who were affected by AD in an acute phase. During the first study phase from Day 1 to Day 14, 10 patients received a silver textile (Group 1), 10 a silver-free textile (Group 2), and 10 prednicarbate ointment (Group 3). In the second phase from Day 15 to Day 28 all patients wore the silver textile, and during the follow-up period from Day 28 to Day 56 no textiles were used. Prednicarbate ointment was allowed as emergency medication, but ointment consumption was measured. The overall severity of the disease was evaluated using the SCORAD index as the primary efficacy parameter. Secondary parameters included severity of pruritus and the patients' assessment of their disease control (uncontrolled, limited, good or complete). Safety tests included hematology, blood chemistry, urinalysis for silver, and physical examination for silver deposits in the skin and mucous membranes.\n The initial SCORAD was 61.6 (IQR 26.6, min. 30.6, max. 99.9). At the end of the Study Phase 1 the SCORAD had improved significantly in the patients of Groups 1 (74.6-29.9, p = 0.005) and 3 (57.8-24.0, p = 0.009). During Study Phase 2 healing of eczema continued in Group 1 (SCORAD 29.9-18.1, p = 0.037), was observed in Group 2 (48.2-24.1, p = 0.015), and remained at an improved level in Group 3 (SCORAD 24-23.5). Consumption of prednicarbate ointment (Phase 1, Phase 2, follow-up period, medians are given): Group 1: 135 g, 10 g, 45 g; Group 2: 13 g, 0 g, 0 g; Group 3: 145 g, 30 g, 90 g. Silver textiles reduced the severity of the pruritus (p = 0.031); silver-free textiles (n.s.) and prednicarbate (n.s.) were less effective. No undesired events were observed.\n The elastic silver textile worn directly against the skin led to an impressive improvement of AD and a reduction in the use of prednicarbate ointment.", "It is recognized that colonization by Staphylococcus aureus (SA) on the skin is one of the factors that can worsen atopic dermatitis (AD). Antibiotics and germicides are not the best choice to remove bacteria from the skin of AD patients, because of problems of irritation to the skin and bacterial resistance. We therefore turned our attention to the biofilm of SA with the aim of removing only SA from the skin surface of AD patients. We found that xylitol (X) and farnesol (F) synergistically inhibited biofilm formation by SA and dissolved biofilm formed in vivo (Part 1).\n To test whether application of AD for 1 week with FX cream can reduce SA without affecting Staphylococcus epidermidis.\n A randomized, double-blind, placebo-controlled right-and-left comparison study was performed. The arms of 17 patients with dry-type AD were applied with skin-care cream including/or not including a 0.02% F and 5% X combination for 1 week. The clinical response, biophysical assessment of the skin surface and counts of skin microflora were recorded before and after 1 week of therapy.\n The ratio of SA in total bacteria at sites to which FX cream had been applied was significantly decreased after 1 week (P = 0.007), compared with before application and with placebo sites (P = 0.045). The mean skin conductance (a parameter indicating the state of hydration of the skin surface) of FX cream sites was increased significantly compared with the conductance before application (P = 0.0001) and at placebo sites (P = 0.002).\n This study provides evidence supporting the idea that cream containing F and X is a useful skin-care agent for atopic dry skin colonized by SA.", "nan", "Atopic dermatitis is commonly colonized with Staphylococcus aureus in high densities.\n Our purpose was to study the effect of topical corticosteroids on the colonization of S. aureus in atopic dermatitis.\n Sixty-six patients were treated with moderately potent, or very potent corticosteroids. Quantification of S. aureus and evaluation of the severity of the eczema was performed before, after 1 week, and after 2 weeks of treatment.\n Fifty-three patients carried S. aureus in the most pronounced lesion before treatment. The colonization was significantly correlated with the severity of the eczema. The density of S. aureus was reduced by topical corticosteroids. The reduction increased with the potency of the corticosteroid and was most pronounced during the first week. S. aureus was eliminated after a successful 2-week treatment with a very potent corticosteroid. Propylene glycol 25% added to a moderately potent corticosteroid did not significantly increase the reduction of S. aureus.\n Topical corticosteroids of sufficient potency reduce the density of S. aureus in atopic dermatitis.", "Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum L. (Saint John's wort).\n In the present half-side comparison study we assessed the efficacy of a cream containing Hypericum: extract standardised to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute Atopic Dermatitis. The study design was a prospective randomised placebo-controlled double-blind monocentric study.\n In twenty one patients suffering from mild to moderate Atopic Dermatitis (mean SCORAD 44.5) the treatment with verum or placebo was randomly allocated to the left or right site of the body, respectively. The patients were treated twice daily over a period of four weeks. Eighteen patients completed the study. The severity of the skin lesions on the left and right site was determined by means of a modified SCORAD-index (primary endpoint).\n The intensity of the eczematous lesions improved on both sites of treatment. However, the hypericum-cream was significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p < 0.05). Skin colonisation with Staphylococcus aureus was reduced by both verum and placebo, showing a trend to better antibacterial activity of the hypericum-cream (p = 0.064). Skin tolerance and cosmetic acceptability was good or excellent with both the hypericum-cream and the vehicle (secondary endpoints).\n Taken together, the present study shows a significant superiority of the hypericum-cream compared to the vehicle in the topical treatment of mild to moderate Atopic Dermatitis. The therapeutic efficacy of the hypericum-cream, however, has to be evaluated in further studies with larger patient cohorts, in comparison to therapeutic standards (i.e. glucocorticoids).", "The addition of an anti-infective to a topical glucocorticoid preparation for superinfected atopic eczema is still controversial. To address this question in the context of the topical glucocorticoids of the non-halogenated double-ester type 0.25% prednicarbate cream was compared to the identical preparation incorporating the same amount of the disinfectant didecyldimethylammoniumchloride in patients suffering from atopic eczema carrying Staphylococcus aureus at a density of more than 10(6) colony-forming units per cm2. One of the preparations was used twice daily over 5 days according to a random plan in a blind fashion. Thereafter treatment was based on either prednicarbate cream or the corresponding vehicle according to clinical needs. Clinical and microbiological evaluation were scheduled for days 0, 6 and 34. Various clinical parameters were addressed individually as well as over all improvement using scores. A total of 143 patients was recruited. The patients of both groups improved rapidly with respect to clinical and microbiological findings. Essentially, there was no difference between the groups. Hence, the addition of an anti-infective to a topical prednicarbate preparation is not to be generally recommended.", "Fifty patients with symmetrical, bilateral lesions of psoriasis, eczematous dermatitis, atopic dermatitis, or neurodermatitis participated in a double-blind paired comparison study in which 0-1% halcinonide (in a cream formulation containing also neomycin and nystatin) was applied to the lesions on one side of the body and 1% hydrocortisone cream to those on the opposite side for two to three weeks. The number of excellent responses to therapy showed the halcinonide combination to be significantly superior (p less than 0-01) to the control cream in all diagnostic categories if considered collectively, and in psoriasis if the responses were grouped according to diagnosis. No adverse reactions occurred during the trial." ]

[ "3799768" ]

[ "Randomized management of the second nonvertex twin: vaginal delivery or cesarean section." ]

[ "Sixty twin deliveries after the thirty-fifth gestational week with vertex-breech and vertex-transverse presentations were managed according to a randomization protocol. Thirty-three parturient women (21 vertex-breech and 12 vertex-transverse presentations) were allocated for vaginal delivery and 27 for cesarean section (18 vertex-breech and nine vertex-transverse). Six pairs of twins in the vaginal delivery group were delivered in a different mode than requested by the protocol (two women underwent cesarean section; in four cases the second twin spontaneously changed to vertex presentation). There were no significant differences between 1- and 5-minute Apgar scores and incidence of neonatal morbidity between the second-born twins in both study groups. Firstborn twins had higher 1-minute Apgar scores than the second-born infants irrespective of route of delivery (p less than 0.05). No case of birth trauma or neonatal death was recorded. Maternal febrile morbidity was significantly higher in the cesarean section group than in the vaginal delivery group (40.7% versus 11.1%, p less than 0.05). These results suggest that in twins with vertex-breech or vertex-transverse presentations after the thirty-fifth week of gestational age the neonatal outcome of the second twin was not significantly influenced by the route of delivery." ]

[ "4603278", "9111457", "9256868", "3511478", "2712613", "2009043", "10332014", "10334751", "6742895" ]

[ "Periarthritis of the shoulder: a controlled trial of physiotherapy.", "Acetic acid iontophoresis and ultrasound for the treatment of calcifying tendinitis of the shoulder: a randomized control trial.", "A randomized, controlled clinical trial of a treatment for shoulder pain.", "Ultrasound therapy of subacromial bursitis. A double blind trial.", "Injections and physiotherapy for the painful stiff shoulder.", "Electromagnetic treatment of shoulder periarthritis: a randomized controlled trial of the efficiency and tolerance of magnetotherapy.", "Ultrasound therapy for calcific tendinitis of the shoulder.", "Treatment of shoulder complaints in general practice: long term results of a randomised, single blind study comparing physiotherapy, manipulation, and corticosteroid injection.", "Frozen shoulder: prospective clinical study with an evaluation of three treatment regimens." ]

[ "nan", "To assess the effects of acetic acid iontophoresis (AAI) and ultrasound on calcifying tendinitis of the shoulder, and to determine the relation between changes in the radiological measures of calcium deposit (CD) and shoulder function.\n Randomized control trial.\n General community, private practice.\n Twenty-two adults (7 men, 15 women) with a calcifying tendinitis of the shoulder, without associated conditions, stratified according to the type of lesions (X-ray: type I, fleecy appearance: type II, homogeneous), were randomly allocated to an experimental (EXP, n = 11) or to a control (CTL, n = 10) group.\n CTL group, no treatment; EXP group, nine treatments including AAI (5% acetic acid solution via the negative electrode, 5mA galvanic current, 20 minutes) followed by continuous ultrasound (0.8w/cm2, 1MHz, 5 minutes).\n Area and density of the CD, passive shoulder abduction (range of motion [ROM]), pain intensity.\n Significant reduction in the area and density of CD (ANCOVA, p = .01 and .03) over time in the EXP and CTL groups, but no significant difference between groups for any of the variables measured. The decrease in the area of CD in type I lesions (n = 5) was larger (Mann-Whitney U test, p < .01) than in type II (n = 16) lesions. The relation was stronger (rs = .90) between changes in area and density of CD than between ROM and pain (rs = -.67). Correlations were weak (rs = .21 to .41) between radiological and functional changes.\n The reduction in CD area and density likely results from a natural process rather than treatment (AAI and ultrasound); type I lesions (resorptive phase) are more likely to display resorption of the CD than type II lesions (formative phase). Reduction of the CD area does not necessary result in a functional improvement.", "The aim of this study was to evaluate the efficacy of a physical therapy approach to the treatment of shoulder pain. Subjects. Sixty-six volunteers with shoulder pain believed to be of local mechanical origin were randomly allocated to either a treatment group or a control group.\n Subjects in the treatment group received 1 month of physical therapy aimed at restoring function of their shoulder muscles. Subjects in the control group received no treatment. Outcome measurements of pain intensity, range of motion (ROM), isometric muscle force, functional impairment, and self-perception of improvement were obtained by blinded assessment.\n Subjects in the treatment group showed improvement in pain-free abduction and flexion ROM, functional impairment, and self-perception of improvement. The control group deteriorated slightly over the experimental period in ROM and functional impairment measures.\n These results suggest that the physical therapy approach used in this study is effective in improving shoulder function in subjects experiencing pain of mechanical origin. The results also provide little evidence of spontaneous recovery over a 1-month period.", "Ultrasound (US) is used widely to treat patients with supraspinatus tendinitis, subacromial bursitis, or adhesive capsulitis (SSA). No double blind studies of US in the treatment of SSA, however, have been conducted. This study was designed to determine whether the addition of US can further decrease pain and increase range of motion in those receiving the usual courses of ROM exercises and nonsteroidal anti-inflammatory drugs (NSAIDs) or ROM exercises in patients with SSA. Twenty patients with SSA were randomized to receive true or sham US three times a week for four weeks. All other aspects of treatment remained constant (ROM exercises and NSAIDs or ROM exercises). The physician, the physical therapist, and the patients were blinded throughout the study regarding the delivery of the true or sham US. Of the multiple variables analyzed (pain, ROM, and function), no significant difference was found between the sham or true US groups. Although the study group was small, the results suggest that US is of little or no benefit when combined with ROM exercises and NSAIDs or ROM exercises in the treatment of SSA.", "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.", "The potential benefit of magnetotherapy was investigated in 47 consecutive outpatients with periarthritis of the shoulder. Using a controlled triple-blind study design, one group of patients received hot pack applications and passive manual stretching and pulley exercises; the other group received the same therapy plus magnetotherapy. Treatment was administered three times a week. For a maximum of three months, a standardized treatment protocol was used. There was no significant improvement in pain reduction or in range of motion with electromagnetic field therapy. After 12 weeks of therapy, the patients who received magnetotherapy showed mean pain scores of 1.5 (+/- .61 SD) at rest, 2.2 (+/- .76 SD) on movement, and 1.9 (+/- .94 SD), on lying, compared to scores for the control group of 1.4 (+/- .65 SD), 2.2 (+/- .7 SD), and 1.9 (+/- .95 SD), respectively. Linear pain scale scores improved from 71 to 21 for both groups. At 12 weeks the gain in range of motion was mean 109 degrees +/- 46.8 in patients receiving electromagnetic field therapy, compared to 122 degrees +/- 33.4 for the controls (not significant). At entry, the functional handicap score was 53.5 for both groups. At 12 weeks, it was 24 for the magnetotherapy group and 17 for the control group (difference not significant). In conclusion, this study showed no benefit from magnetotherapy in the pain score, range of motion, or improvement of functional status in patients with periarthritis of the shoulder.", "Although ultrasound therapy is used to treat calcific tendinitis of the shoulder, its efficacy has not been rigorously evaluated. We conducted a randomized, double-blind comparison of ultrasonography and sham insonation in patients with symptomatic calcific tendinitis verified by radiography. Patients were assigned to receive 24 15-minute sessions of either pulsed ultrasound (frequency, 0.89 MHz; intensity, 2.5 W per square centimeter; pulsed mode, 1:4) or an indistinguishable sham treatment to the area over the calcification. The first 15 treatments were given daily (five times per week), and the remainder were given three times a week for three weeks. Randomization was conducted according to shoulders rather than patients, so a patient with bilateral tendinitis might receive either or both therapies.\n We enrolled 63 consecutive patients (70 shoulders). Fifty-four patients (61 shoulders) completed the study. There were 32 shoulders in the ultrasound-treatment group and 29 in the sham-treatment group. After six weeks of treatment, calcium deposits had resolved in six shoulders (19 percent) in the ultrasound-treatment group and decreased by at least 50 percent in nine shoulders (28 percent), as compared with respective values of zero and three (10 percent) in the sham-treatment group (P=0.003). At the nine-month follow-up visit, calcium deposits had resolved in 13 shoulders (42 percent) in the ultrasound-treatment group and improved in 7 shoulders (23 percent), as compared with respective values of 2 (8 percent) and 3 (12 percent) in the sham-treatment group (P=0.002). At the end of treatment, patients who had received ultrasound treatment had greater decreases in pain and greater improvements in the quality of life than those who had received sham treatment; at nine months, the differences between the groups were no longer significant.\n In patients with symptomatic calcific tendinitis of the shoulder, ultrasound treatment helps resolve calcifications and is associated with short-term clinical improvement.", "nan", "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." ]

[ "15930418" ]

[ "A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults." ]

[ "The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults.\n We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine (\"zoster vaccine\"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia.\n More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild.\n The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.\n Copyright 2005 Massachusetts Medical Society." ]

[ "6753769" ]

[ "Apnoea of immaturity. 1. A controlled trial of theophylline and face mask continuous positive airways pressure." ]

[ "A randomised controlled trial of theophylline versus face-mask continuous positive airways pressure (CPAP) treatment for recurrent apnoea of immaturity was carried out in 32 infants of 25 to 32 weeks' gestation. Continuous recording of electrocardiogram and impedence pneumogram added objective assessment to the nurses' observations for 11 courses of treatment. The CPAP group had more adverse perinatal factors but the frequency of apnoeic attacks before treatment was comparable. Infants given theophylline had a greater reduction in the incidence of prolonged apnoeic attacks, and this difference persisted after allowing for the effect of perinatal complications. Continuous recordings showed a greater reduction in episodes of bradycardia of less than or equal to 80/minute with theophylline. Five of 18 infants given theophylline needed intermittent positive pressure ventilation for apnoea compared with 12 of 14 given CPAP. The poor response in 17 of 32 infants suggests a need for a more effective method of preventing or treating apnoea in very immature babies, in whom adverse perinatal factors often coexist." ]

[ "15821191", "16304304", "10911005", "12759479", "8583804", "10588623", "12728160", "11156078" ]

[ "Lung volume reduction surgery vs medical treatment: for patients with advanced emphysema.", "Comparison of lung volume reduction surgery and physical training on health status and physiologic outcomes: a randomized controlled clinical trial.", "Effect of lung-volume-reduction surgery in patients with severe emphysema.", "A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.", "A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema.", "Prospective randomized trial comparing bilateral lung volume reduction surgery to pulmonary rehabilitation in severe chronic obstructive pulmonary disease.", "Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease.", "Buttressing the staple line in lung volume reduction surgery: a randomized three-center study." ]

[ "To contribute to the knowledge on the therapeutic value of lung volume reduction surgery (LVRS).\n Two similar, independently conceived and conducted, multicenter, randomized clinical trials.\n The Canadian Lung Volume Reduction (CLVR) study and the Overholt-Blue Cross Emphysema Surgery Trial (OBEST).\n Using a fixed-effects meta-analysis, the 6-month results produced by the addition of LVRS to optimal medical therapy were compared to those obtained from optimal medical therapy alone. Patients were required to have severe emphysema, marked airflow limitation (ie, FEV(1), 15 to 40% predicted), hyperinflation (total lung capacity [TLC], > 120% predicted), CO(2), < 55 mm Hg, and measurable dyspnea (chronic respiratory disease questionnaire [CRDQ] scores </= 4 for the CLVR study, or Medical Research Council dyspnea scale >/= 1 for the OBEST). Optimal medical therapy included pulmonary rehabilitation in both arms of both studies.\n The CLVR study randomized 58 patients and the OBEST randomized 35 patients for a total of 93 patients. Of these, 54 patients were randomized to undergo surgery, and 39 patients were randomized to receive medical treatment. The 6-month mortality rate (including operative mortality) in the surgical and medical cohorts was similar (5.6% vs 5.1%, respectively). A comparison of the medical and surgical arms of the combined CLVR study/OBEST population showed that LVRS was associated with a higher FEV(1) (167 mL or 24% predicted; 95% confidence interval [CI], 29 to 304; p = 0.017), lower residual volume (-1,342 mL or 24.5% predicted; 95% CI, -1,844 to -840; p < 0.001), lower TLC (-1,044 mL or 13% predicted; 95% CI, -1483 to -605; p < 0.001), and higher 6-min walk distance (148.8 feet; 95% CI, 24.3 to 273.2; p = 0.019). Each domain of the CRDQ showed statistically significant improvement in the surgical arm of the study, but not in the medical arm. The summary physical component scale of the Medical Outcomes Study 36-item short form (SF-36) was also more favorable in the LVRS cohort (6.9; 95% CI, 2.86 to 10.90; p < 0.001). The summary mental component scale of the SF-36 did not show a statistically significant difference between the two groups.\n Six months after randomization, LVRS produced better palliation than optimal medical therapy in patients with advanced emphysema.", "In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements.\n After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year.\n All seven thoracic surgery centers in Sweden.\n All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS.\n Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively.\n Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months.\n In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.", "Although many patients with severe emphysema have undergone lung-volume-reduction surgery, the benefits are uncertain. We conducted a randomized, controlled trial of the surgery in patients with emphysema. Patients with isolated bullae were excluded because such patients are known to improve after bullectomy.\n Potentially eligible patients were given intensive medical treatment and completed a smoking-cessation program and a six-week outpatient rehabilitation program before random assignment to surgery or continued medical treatment. After 15 patients had been randomized, the entry criteria were modified to exclude patients with a carbon monoxide gas-transfer value less than 30 percent of the predicted value or a shuttle-walking distance of less than 150 m, because of the deaths of 5 such patients (3 treated surgically and 2 treated medically).\n Of the 174 subjects who were initially assessed, 24 were randomly assigned to continued medical treatment and 24 to surgery. At base line in both groups, the median forced expiratory volume in one second (FEV1) was 0.75 liter, and the median shuttle-walking distance was 215 m. Five patients in the surgical group (21 percent) and three patients in the medical group (12 percent) died (P=0.43). After six months, the median FEV1 had increased by 70 ml in the surgical group and decreased by 80 ml in the medical group (P=0.02). The median shuttle-walking distance increased by 50 m in the surgical group and decreased by 20 m in the medical group (P=0.02). There were similar changes on a quality-of-life scale and similar changes at 12 months of follow-up. Five of the 19 surviving patients in the surgical group had no benefit from the treatment.\n In selected patients with severe emphysema, lung-volume-reduction surgery can improve FEV1, walking distance, and quality of life. Whether it reduces mortality is uncertain.", "Lung-volume-reduction surgery has been proposed as a palliative treatment for severe emphysema. Effects on mortality, the magnitude and durability of benefits, and criteria for the selection of patients have not been established.\n A total of 1218 patients with severe emphysema underwent pulmonary rehabilitation and were randomly assigned to undergo lung-volume-reduction surgery or to receive continued medical treatment.\n Overall mortality was 0.11 death per person-year in both treatment groups (risk ratio for death in the surgery group, 1.01; P=0.90). After 24 months, exercise capacity had improved by more than 10 W in 15 percent of the patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P<0.001). With the exclusion of a subgroup of 140 patients at high risk for death from surgery according to an interim analysis, overall mortality in the surgery group was 0.09 death per person-year, as compared with 0.10 death per person-year in the medical-therapy group (risk ratio, 0.89; P=0.31); exercise capacity after 24 months had improved by more than 10 W in 16 percent of patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P<0.001). Among patients with predominantly upper-lobe emphysema and low exercise capacity, mortality was lower in the surgery group than in the medical-therapy group (risk ratio for death, 0.47; P=0.005). Among patients with non-upper-lobe emphysema and high exercise capacity, mortality was higher in the surgery group than in the medical-therapy group (risk ratio, 2.06; P=0.02).\n Overall, lung-volume-reduction surgery increases the chance of improved exercise capacity but does not confer a survival advantage over medical therapy. It does yield a survival advantage for patients with both predominantly upper-lobe emphysema and low base-line exercise capacity. Patients previously reported to be at high risk and those with non-upper-lobe emphysema and high base-line exercise capacity are poor candidates for lung-volume-reduction surgery, because of increased mortality and negligible functional gain.\n Copyright 2003 Massachusetts Medical Society", "Two procedures (laser bullectomy and lung reduction surgery with staples) are currently available for the surgical treatment of patients with diffuse emphysema. We compared the efficacy of these two surgical approaches in 72 patients, aged 67 +/- 7 years (mean +/- standard deviation), who had diffuse emphysema scored as severe on computed tomography and severe fixed expiratory airflow obstruction. The patients were prospectively randomized to undergo either neodymium:yttrium aluminum garnet contact laser surgery (n = 33) or stapled lung reduction surgery (n = 39) by unilateral thoracoscopy. The operative mortalities were 0% and 2.5%, respectively. No significant differences were noted between the groups (p < 0.05) with respect to operating time, hospital days, or air leakage for more than 7 days. However, a delayed pneumothorax developed in six patients (18%) who had laser treatment (p = 0.005). The operations eliminated dependency on supplemental oxygen in 52% of the laser group and 87.5% of the stapled lung reduction group (p = 0.02). The mean postoperative improvement in the forced expiratory volume in 1 second at 6 months was significantly greater for the patients undergoing the staple technique (32.9% vs 13.4%, p = 0.01) than for the laser treatment group.", "Several uncontrolled studies report improvement in lung function, gas exchange, and exercise capacity after bilateral lung volume reduction surgery (LVRS). We recruited 200 patients with severe chronic obstructive pulmonary disease (COPD) for a prospective randomized trial of pulmonary rehabilitation versus bilateral LVRS with stapling resection of 20 to 40% of each lung. Pulmonary function tests, gas exchange, 6-min walk distance, and symptom-limited maximal exercise testing were done in all patients at baseline and after 8 wk of rehabilitation. Patients were then randomized to either 3 additional months of rehabilitation or LVRS. Thirty-seven patients met study criteria and were enrolled into the trial. Eighteen patients were in the medical arm; 15 of 18 patients completed 3 mo of additional pulmonary rehabilitation. Thirty-two patients underwent LVRS (19 in the surgical arm, 13 crossover from the medical arm). After 8 wk of pulmonary rehabilitation, pulmonary function tests remained unchanged compared with baseline data. However, there was a trend toward a higher 6-min walk distance (285 +/- 96 versus 269 +/- 91 m, p = 0.14) and total exercise time on maximal exercise test was significantly longer compared with baseline values (7.4 +/- 2.1 versus 5.8 +/- 1.7 min, p < 0.001). In 15 patients who completed 3 mo of additional rehabilitation, there was a trend to a higher maximal oxygen consumption (V O(2)max) (13.3 +/- 3.0 versus 12.6 +/- 3.3, p < 0.08). In contrast, at 3 mo post-LVRS, FVC (2.79 +/- 0.59 versus 2.36 +/- 0.55 L, p < 0.001) and FEV(1) (0.85 +/- 0.3 versus 0.65 +/- 0.16 L, p < 0.005) increased whereas TLC (6.53 +/- 1.3 versus 7.65 +/- 2.1 L, p < 0.001) and residual volume (RV) (3.7 +/- 1.2 versus 4.9 +/- 1.1 L, p < 0.001) decreased when compared with 8 wk postrehabilitation data. In addition, Pa(CO(2)) decreased significantly 3 mo post-LVRS compared with 8 wk postrehabilitation. Six-minute walk distance (6MWD), total exercise time, and V O(2)max were higher after LVRS but did not reach statistical significance. However, when 13 patients who crossed over from the medical to the surgical arm were included in the analysis, the increases in 6MWD (337 +/- 99 versus 282 +/- 100 m, p < 0.001) and V O(2)max (13.8 +/- 4 versus 12.0 +/- 3 ml/kg/min, p < 0.01) 3 mo post-LVRS were highly significant when compared with postrehabilitation data. The Sickness Impact Profile (SIP), a generalized measure of quality of life (QOL), was significantly improved after 8 wk of rehabilitation and was maintained after 3 mo of additional rehabilitation. A further improvement in QOL was observed 3 mo after LVRS compared with the initial improvement gained after 8 wk of rehabilitation. There were 3 (9.4%) postoperative deaths, and one patient died before surgery (2.7%). We conclude that bilateral LVRS, in addition to pulmonary rehabilitation, improves static lung function, gas exchange, and QOL compared with pulmonary rehabilitation alone. Further studies need to evaluate the risks, benefits, and durability of LVRS over time.", "The clinical value of LVRS has been questioned in the absence of trials comparing it with pulmonary rehabilitation, the prevailing standard of care in COPD. Patients with heterogeneous emphysema are more likely to benefit from volume reduction than those with homogeneous disease. Disease specific quality of life is a responsive interpretable outcome that enables health professionals to identify the magnitude of the effect of an intervention across several domains.\n Non-smoking patients aged <75 years with severe COPD (FEV(1) <40% predicted, FEV(1)/FVC <0.7), hyperinflation, and evidence of heterogeneity were randomised to surgical or control groups after pulmonary rehabilitation and monitored at 3 month intervals for 12 months with no crossover between the groups. The primary outcome was disease specific quality of life as measured by the Chronic Respiratory Questionnaire (CRQ). Treatment failure was defined as death or functional decline (fall of 1 unit in any two domains of the CRQ). Secondary outcomes included pulmonary function and exercise capacity.\n LVRS resulted in significant between group differences in each domain of the CRQ at 12 months (change of 0.5 represents a small but important difference): dyspnoea 1.9 (95% confidence interval (CI) 1.3 to 2.6; p<0.0001); emotional function 1.5 (95% CI 0.9 to 2.1; p<0.0001); fatigue 2.0 (95% CI 1.4 to 2.6; p<0.0001); mastery 1.8 (95% CI 1.2 to 2.5; p<0.0001). In the control group one of 27 patients died and 16 experienced functional decline over 12 months. In the surgical group four of 28 patients died and three experienced functional decline (hazard ratio = 3.1 (95% CI 1.3 to 7.6; p=0.01). Between group improvements (p<0.05) in lung volumes, flow rates, and exercise were sustained at 12 months (RV -47% predicted (95% CI -71 to -23; p=0.0002); FEV(1) 0.3 l (95% CI 0.1 to 0. 5; p=0.0003); submaximal exercise 7.3 min (95% CI 3.9 to 10.8; p<0.0001); 6 minute walk 66 metres (95% CI 32 to 101; p=0.0002).\n In COPD patients with heterogeneous emphysema, LVRS resulted in important benefits in disease specific quality of life compared with medical management, which were sustained at 12 months after treatment.", "The intention of buttressing the staple line in lung volume reduction surgery is to reduce air leaks and to shorten the hospital stay. A randomized three-center study was carried out to test this hypothesis.\n Sixty-five patients with a mean age of 59.2 +/- 1.2 years underwent bilateral lung volume reduction surgery by video-assisted thoracoscopy using endoscopic staplers (ET 45B; Ethicon Endo-Surgery, Cincinnati, OH) either without or with bovine pericardium for buttressing (Peri-Strips Dry; Bio-Vascular, Inc, Saint Paul, MN). There were no differences between the control and treatment groups in lung function, degree of dyspnea, and arterial blood gases before and 3 months after LVRS.\n Seven patients (3 in the treatment group) needed a reoperation because of persistent air leak. The median duration of air leaks was shorter in the treatment group (0.0 day [range, 0 to 28 days versus 4 days [range, 0 to 27 days); p < 0.001), confirmed by a shorter median drainage time in this group (5 days [range, 1 to 35 days] versus 7.5 days [range, 2 to 29 days); p = 0.045). Hospital stay was comparable between the two groups (9.5 days [range, 6 to 44 days] versus 12.0 days [range, 5 to 46 days]; p = 0.14).\n Buttressing the staple line significantly shortens the duration of air leaks and the drainage time. As hospital stay did not differ significantly between the two groups, cost-effectiveness may depend on the local situation." ]

[ "6829635", "2372330", "3966507" ]

[ "External physical stimulation of the human fetus during episodes of low heart rate variation.", "Effect of vibratory acoustic stimulation on the duration of fetal heart rate monitoring tests.", "Antepartum fetal heart rate testing. XII. The effect of manual manipulation of the fetus on the nonstress test." ]

[ "The effect of shaking the fetus through the maternal abdomen during episodes of low (nonreactive) fetal heart rate variation was studied in 10 healthy nulliparous women near term. Heart rate monitoring from an abdominal electrocardiogram was combined with real-time scanning for body movements and fetal breathing. In each fetus two episodes of low variation were examined, one during which external stimulation was performed and one as a control without stimulation. There were no differences between the groups, with or without stimulation, in the duration of the nonreactive trace or heart rate variation or in the incidence of breathing or body movements. Therefore, shaking the fetus during a nonreactive heart rate episode has no useful purpose. The results are comprehensible in the light of fetal and neonatal behavioral states.", "The ability of vibratory acoustic stimulation to shorten the duration of antepartum fetal heart rate monitoring was investigated by a randomized controlled trial. Vibratory acoustic stimulation did not shorten the overall duration of testing. This failure to improve the performance of antepartum monitoring appeared to result from prolonged accelerations, which complicated one third of the tests in which vibratory acoustic stimulation was employed. Further investigation is warranted using less profound methods of fetal stimulation.", "A prospective study of 790 patients was performed in order to examine the role of manual manipulation of the fetus in the nonstress test. The patients were assigned randomly to two groups based on the last two digits of their hospital number. The odd-numbered patients underwent manual manipulation of the fetus prior to the onset of the nonstress test; the even-numbered patients did not. There was no significant difference between the two groups with respect to the indications for testing and the total number of tests. There was no statistically significant difference between the two groups with respect to the ratio of reactive to nonreactive nonstress tests and the mean duration of testing. Simple manual manipulation of the fetus does not seem to change the outcome in antepartum fetal heart rate testing when the nonstress test is the primary one." ]

[ "2195013", "6370980", "2491140", "6370981", "3624611", "7380822", "7714303", "6760217", "6387360", "6406442", "9283926", "3700932", "8018452", "8277144" ]

[ "Pharmacologic treatment of major depression for elderly patients in residential care settings.", "A two-center double-blind study of nomifensine, imipramine, and placebo in depressed geriatric outpatients.", "The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.", "A double-blind comparative evaluation of the efficacy and safety of nomifensine, imipramine, and placebo in depressed geriatric outpatients.", "Group cognitive therapy and alprazolam in the treatment of depression in older adults.", "Treatment of geriatric depression with trazodone, imipramine, and placebo: a double-blind study.", "Moclobemide and nortriptyline in elderly depressed patients. A randomized, multicentre trial against placebo.", "[Clinical double blind comparison of diclofensine and placebo in geriatric patients with depressive syndromes].", "[Viloxazine in the treatment of depression in the aged. Double-blind placebo study].", "Safety and efficacy of bupropion in elderly patients: preliminary observations.", "Placebo-controlled treatment trial of depression in elderly physically ill patients.", "Effective low dose tricyclic antidepressant treatment for depressed geriatric rehabilitation patients. A double-blind study.", "The effect of low dose lofepramine in depressed elderly patients in general medical wards.", "Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression." ]

[ "A significant drug-placebo difference was found in a double-blind, placebo-controlled study of nortriptyline for treatment of major depression among frail elderly patients living in an institutional setting. This finding confirms the validity of the DSM-III-R diagnosis of major depression and establishes the need for specific psychiatric services for the chronically ill elderly living in nursing homes and congregate housing facilities. The incidence of adverse events requiring early termination of treatment was 34%, demonstrating the vulnerability of these patients and their need for careful monitoring during treatment. High levels of self-care disability and low levels of serum albumin were both associated with decreased therapeutic responses, demonstrating the need for further research on psychopathology in these settings.", "Both nomifensine and imipramine were superior to placebo in a 4-week double-blind study involving 63 geriatric patients (greater than 60 years) with primary affective disorder-depression. Significant improvement in the active drug groups was demonstrated on the Hamilton Depression Rating Scale, Clinical Global Impressions, Brief Psychiatric Rating Scale, and Hopkins Symptom Check List. Analysis of laboratory and physical examination data, including ECGs, revealed no clinically significant changes associated with either drug. Compared to the imipramine group, nomifensine-treated patients showed a more rapid rate of improvement and a lower incidence of discomforting side effects.", "Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.", "Nomifensine, imipramine, and placebo were compared in 61 depressed geriatric outpatients over a 35-day period. At average daily doses of 150 mg, nomifensine and imipramine were significantly more effective than placebo in reducing symptoms of depression in this sample of elderly depressed patients. Nomifensine and imipramine were generally comparable in clinical effect; 78% of the nomifensine-treated patients were rated as improved at the end of treatment as compared with 64% of imipramine and 20% of placebo patients. The findings suggest a more favorable side effect profile for nomifensine, which was associated with a lower frequency of sedating and anticholinergic effects than was seen in the imipramine group.", "nan", "Sixty unipolar depressed geriatric outpatients were subjects in a double-blind study of a new antidepressant, trazodone, versus imipramine and placebo. Over the four week study, patients in the two active medication groups improved significantly compared to placebo on both observer and self-ratings. Although imipramine and trazodone had similar therapeutic efficacy, trazodone was judged to have fewer side effects than imipramine, suggesting that trazodone may have particular clinical utility in the geriatric population which is especially vulnerable to cardiovascular and anticholinergic side effects.", "Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either moclobemide or placebo.", "The objective of this double-blind trial was to assess the effect of diclofensine on geriatric patients with depressive syndromes in comparison to placebo. 40 patients (age 60-75 years) were treated for 3 weeks with a mean daily dose of 57.5 mg diclofensine or placebo. Diclofensine was found effective in 18 (= 90%) cases (placebo 60%) after 2.9 days on an average (placebo, 4.2 days), mostly having a mood elevating effect and in only 2 cases (placebo 1) having a stimulatory effect. The results of the global assessments, the Hamilton depression scale, the d2-test, the block design test and the mood scale (Befindlichkeitsskala) demonstrated a statistically significant superiority of diclofensine over placebo. The critical flicker frequency, on the other hand, was not able to differentiate significantly between the two drugs. The tolerance was considered as very good in all cases. Unwanted effects were observed in 13 patients (= 65%) of the diclofensine group and in 9 patients (= 45%) of the placebo group. They disappeared in most cases within one week after their appearance. According to this trial diclofensine can be described as a well tolerated drug without pronounced anticholinergic side effects, capable of improving depressive states faster and more effectively than placebo.", "nan", "The efficacy and safety of bupropion, an atypical antidepressant, were assessed in depressed patients aged 55 and above. Data were analyzed for 38 patients who completed 4 weeks of double-blind treatment with bupropion in maximum doses of 150 or 450 mg/day; imipramine, up to 200 mg/day; or placebo. Preliminary results suggest that bupropion does have antidepressant activity and is well tolerated in this population. A particular advantage is suggested in terms of cardiovascular side effects.", "To determine the response of physically ill elderly depressed patients to treatment.\n Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine.\n Response rate as defined by the 17-item Hamilton Depression Rating Scale.\n Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02).\n The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important.", "The efficacy of low doses (10 to 20 mg daily) of doxepin in the treatment of depressive disorders in elderly inpatients was assessed by a double-blind study in 24 patients. The patients were treated for a three-week period to test for an early response. The Hamilton Depression Scale and the Geriatric Depression Scale were used to quantify symptoms of depression. The patients treated with doxepin had a significantly greater reduction in depressive symptoms than did those who received a placebo. No side effects were found and there were no major differences in the degree of physical dependency between the doxepin and placebo groups. A depressive disorder is a common occurrence among elderly inpatients and the effectiveness of low dose doxepin therapy without demonstrable side effects argues for the active treatment for this condition.", "A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.", "Major depression during later life represents a clinical challenge. Conventional antidepressant pharmacotherapy is relatively less well tolerated in geriatric patients compared with younger patients. Despite the striking impairments associated with this disorder, clinical investigations into the relative risk-benefit ratio of various depression treatment strategies have been limited. In this multicentre, placebo-controlled, double-blind trial with fluoxetine, 671 major depressed (DSM-III-R-compatible) outpatients aged 60 years or older were evaluated. The 21-item Hamilton Depression Rating Scale (HAMD21) response (p = 0.014) and remission (p = 0.008) criteria favoured fluoxetine over placebo. Analysis of the treatment effect on change in the HAMD21 factors (anxiety/somatization, cognitive disturbance, psychomotor retardation, and sleep disturbance) revealed advantages for fluoxetine within the cognitive disturbance and psychomotor retardation factors. Overall, the rate of discontinuation for an adverse event between fluoxetine (11.6%) and placebo (8.6%) was not statistically significant. Baseline HAMD21 factor scores were not predictive of adverse events leading to premature treatment discontinuation. Fluoxetine, 20 mg/day, is a well-tolerated and effective treatment option in the management of geriatric major depression." ]

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[ "Randomized trial of 3 different regimens of combination chemotherapy in patients receiving simultaneously a hormonal treatment for advanced breast cancer.", "A new six-drug antiblastic regimen (R 14) at low doses (micropolychemotherapy) compared to CMF in the treatment of metastatic breast cancer: phase III study.", "Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193).", "A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project.", "Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.", "Combination chemotherapy with cmf (cyclophosphamide, methotrexate, 5-Fluorouracil) versus cnf (mitoxantrone, 5-Fluorouracil, cyclophosphamide) in advanced breast-cancer - a multicenter randomized study.", "Chemotherapy of advanced breast cancer: a randomized trial of vincristine, Adriamycin, and cyclophosphamide (VAC) versus cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP).", "Chemotherapy of advanced breast cancer. Results of a controlled trial comparing two three-drug regimens.", "A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study.", "Combination or mild single agent chemotherapy for advanced breast cancer? CMF vs epirubicin measuring quality of life.", "Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer.", "A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.", "Low dose chemotherapy of metastatic breast cancer with cyclophosphamide, adriamycin, methotrexate, 5-fluorouracil (CAMF) versus sequential cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and adriamycin.", "Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. Cancer and Leukemia Group B.", "Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors.", "A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer.", "Response and survival in advanced breast cancer after two non-cross-resistant combinations.", "Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer--a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group. Danish Breast Cancer Cooperative Group (DBCG).", "Comparison of induction chemotherapies for metastatic breast cancer. An Eastern Cooperative Oncology Group Trial.", "Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies.", "Cyclophosphamide, adriamycin and platinum (CAP) combination chemotherapy, a new effective approach in the treatment of disseminated breast cancer. Preliminary report.", "Controlled evaluation of adriamycin (NSC-123127) in patients with disseminated breast cancer.", "Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial.", "Mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) versus intravenous cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in first-line chemotherapy for patients with metastatic breast carcinoma: a randomized phase II trial.", "Combination chemotherapy for metastatic breast cancer: comparison of multiple drug therapy with 5-fluorouracil, cytoxan and prednisone with adriamycin or adrenalectomy.", "Comparison of four-combination chemotherapy programs in metastatic breast cancer: comparison of multiple drug therapy with cytoxan, 5-FU and prednisone versus cytoxan and adriamycin, versus cytoxan, 5-FU and adriamycin, versus cytoxan, 5-FU and prednisone alternating with cytoxan and adriamycin.", "Combination chemotherapy and adriamycin in patients with advanced breast cancer. A Southwest Oncology Group study.", "Randomized trial to compare the efficacy and toxicity of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with methotrexate mitoxantrone (MM) in advanced carcinoma of the breast.", "A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer.", "Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study." ]

[ "We report the results of a randomized trial carried out by the Swiss Group for Clinical Cancer Research (SAKK) and in which 230 patients with advanced breast cancer receiving concurrently a hormonal treatment (oophorectomy for pre- and tamoxifen for postmenopausal women) were randomly allocated to three different regimens of combination chemotherapy. The therapeutic results registered with the two more intensive combinations (LMP/FVP and LMFP/ADM) were similar with regard to response rates, time to progression and survival. The patients receiving the low-dose chemotherapy lmfp showed a statistically significant lower response rate (32%, P less than 0.001) and a shorter survival (P = 0.03) than the results observed in patients treated with the two other regimens. This difference was particularly pronounced, at least regarding survival, in the following subgroups: postmenopausal women, patients with a poor performance status, dominant visceral lesions, two sites of disease and a disease-free interval longer than 12 months. Patients with bony metastases as dominant lesion fared similarly with all three regimens of chemotherapy. This latter subset of advanced breast cancer patients should probably be spared too intensive cytotoxic treatment. This is, to our knowledge, the first report of a randomized trial showing an evident correlation between response rate and survival in various subgroups of patients with advanced breast cancer treated with different chemotherapeutic regimens.", "Two groups of 23 patients each, having advanced breast cancer, entered this prospective and randomized study. One group was treated with the conventional schedule of CMF (cyclophosphamide 100 mg/m2/po from the first to the 14th day, methotrexate 40 mg/m2/iv the first and the 8th day, 5-fluorouracil 600 mg/m2/iv the first and the 8th day), and the other was treated with a new six-drug regimen, administered at low doses (R 14: cyclophosphamide 2 mg/kg/iv, vincristine 0.01 mg/kg/iv, vinblastine 0.1 mg/kg/iv, the first day and 5-fluorouracil 5 mg/kg/iv, methotrexate 0.7 mg/kg/iv, adriamycin 0.5 mg/kg/iv the 2nd day every 21 days). The remission rate was 35% (8/23) and 39% (9/23) for CMF and R 14 respectively. The median duration of objective remission was 6 months for CMF and 5 months for R 14 regimen. The median survival time of responding patients was 18 months for CMF and 14 months for R 14. This study shows that the new six-drug regimen at low doses is effective (regarding subjective, objective response and survival rate), and its toxicity is no higher than that of CMF (the incidence of leukopenia was significantly lower during the first course). Therefore, R 14 should be considered an alternative regimen to CMF in the treatment of advanced and, possibly, early breast cancer. The advantages for using R 14 are: 1) it is less toxic (a single dose is a very small amount of medicine compared to what is usually administered), 2) an iv administration always follows a therapeutic program (while in a CMF schedule cyclophosphamide is self-administered by the patient).", "Between February 1993 and September 1995, 739 patients with metastatic breast cancer were entered on an Intergroup trial (E1193) comparing doxorubicin (60 mg/m(2)), paclitaxel (175 mg/m(2)/24 h), and the combination of doxorubicin and paclitaxel (AT, 50 mg/m(2) and 150 mg/m(2)/24 h, plus granulocyte colony-stimulating factor 5 mg/kg) as first-line therapy. Patients receiving single-agent doxorubicin or paclitaxel were crossed over to the other agent at time of progression.\n Patients were well balanced for on-study characteristics.\n Responses (complete response and partial response) were seen in 36% of doxorubicin, 34% of paclitaxel, and 47% of AT patients (P =.84 for doxorubicin v paclitaxel, P =.007 for v AT, P =.004 for paclitaxel v AT). Median time to treatment failure (TTF) is 5.8, 6.0, and 8.0 months for doxorubicin, paclitaxel, and AT, respectively (P =.68 for doxorubicin v paclitaxel, P =.003 for doxorubicin v AT, P =.009 for paclitaxel v AT). Median survivals are 18.9 months for patients taking doxorubicin, 22.2 months for patients taking paclitaxel, and 22.0 months for patients taking AT (P = not significant). Responses were seen in 20% of patients crossing from doxorubicin --> paclitaxel and 22% of patients crossing from paclitaxel --> doxorubicin (P = not significant). Changes in global quality-of-life measurements from on-study to week 16 were similar in all three groups.\n (1) doxorubicin and paclitaxel, in the doses used here, have equivalent activity; (2) the combination of AT results in superior overall response rates and time to TTF; and (3) despite these results, combination therapy with AT did not improve either survival or quality of life compared to sequential single-agent therapy.", "In an ongoing prospective randomized study, 113 evaluable patients have received either a three-drug combination that included cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) or a five-drug combination including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisone (CMFVP) given intermittently 1 week out of 4. Responses (64%), median duration of response (32 weeks), and median duration of disease control (32 weeks) achieved with CAF were superior to those achieved with CMFVP (37%, 22 weeks, 17 weeks, respectively). Morbidity secondary to CAF was significant, with nausea and vomiting, malaise, total alopecia, and granulocytopenia being the main features.", "To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival ¿PFS) and to explore the degree of cross-resistance between the two agents.\n Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m(2), intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression.\n Objective response in first-line therapy was significantly better (P =.003) for doxorubicin (response rate ¿RR, 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P <.001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P =.38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control.\n At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.", "A multicentric randomized study was conducted to compare the CNF regimen (cyclophosphamide at 600 mg/m2/iv, mitoxantrone at 10 mg/m2/iv, 5-fluorouracil at 600 mg/m2/iv) with the CMF regimen (methotrexate at 40 mg/m2/iv instead of mitoxantrone) administered every 3 weeks to previously untreated locally advanced or metastatic breast cancer patients. In 119 patients evaluable for therapeutic response, complete plus partial response rate was 44% for CNF and 29% for CMF (p>0.05; 95% C.I.: CNF=32%-56%, CMF=18%-40%). No statistically significant difference regarding time to progression, over survival or response to second-line chemotherapy with Epidoxorubicin was observed between the two regimens. Both regimens were well tolerated, but the percent of alopecia and leucopenia was significantly higher in the CNF patient group (31% versus 5% and 18% versus 0%, respectively; p<0.01). In conclusion, CNF was demonstrated to be slightly more toxic but more effective as compared to CMF (global response: 44% versus 29%, respectively). These findings should be taken into consideration when planning future studies of adjuvant chemotherapy.", "Fifty-one patients with metastatic breast cancer were randomly allocated to receive either a four drug combination consisting of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or a combination of vincristine, Adriamycin, and cyclophosphamide (VAC) with cross-over on relapse. Objective responses were seen in 17 of 26 patients (65%) in the CMFP group and in 14 of 25 patients (56%) in the VAC group, but this difference was not statistically significant. The median duration of response for each group was one year. The estimated median survival was greater for the CMFP group, but this was not significant. Toxicity was more severe with the VAC regimen. It is concluded that there is no therapeutic advantage of the VAC over the CMFP regimen.", "nan", "The therapeutic effectiveness of intermittent vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone ( CMFVP -C, 86 patients), intermittent CMFVP ( CMFVP -I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP -C (50%, p = 0.003) and to CMFVP -I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP -I (7 months) (p less than 0.01), and tended to be superior to CMFVP -C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP -I (13 months) (p = 0.01), but not over CMFVP -C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP -I (18 months) and CMFVP -C (21 months). The CMFVP -C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens.", "Forty patients with advanced breast cancer, randomised to receive CMF or weekly low dose Epirubicin, were evaluated by UICC criteria of response and WHO toxicity criteria, in addition to three QoL instruments: the 'Qualitator' daily diary card, 4 weekly Nottingham Health Profile (NHP) and Linear Analogue Self-Assessment (LASA). Response rates were 58% for CMF and 29% for epirubicin (chi 2 = 3.51, 1 d.f., P > 0.05). Median time to treatment failure was 24 weeks for CMF, 7 weeks for epirubicin (P < 0.05) but survival was similar in both groups. Survival was better for responders than for non-responders (medians 87 and 30 weeks, P = 0.02). CMF caused more objective alopecia (P < 0.001), nausea and vomiting (P < 0.001) and haematological toxicity (P < 0.02). However, QoL measures only recorded a significant difference in energy and pain, influenced primarily by the non-responders in each treatment group but with no difference in overall global scores. Scores for responders, irrespective of treatment, were better to start with (LASA P = 0.001); at 12 weeks, scores had improved (Qualitator P < 0.05; NHP P < 0.05). Scores in non-responders showed no change. In this small study aggressive chemotherapy gave better response and similar survival without impairing Quality of life overall. Detailed QoL measurement should be integral to all cancer chemotherapy trials.", "Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF or CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.", "We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.", "Seventy-eight advanced breast cancer patients with hormone-resistant disease or visceral metastases were randomized to receive either of two low dose regimens consisting of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), and Adriamycin (A) as their initial chemotherapy. One group was treated with CAMF, and the other with CMF until progression, followed by A (CMF leads to A). C was given at 50 mg/m2, po, days 1-14; M at 20 mg/m2, F at 300 mg/m2, and A at 20 mg/m2, iv, days 1 and 8 of each 28-day cycle. The response rates for CAMF vs. CMF did not differ significantly (complete and partial responses-62% vs. 49%; stabilizations-23% vs. 31%). Responses by site of metasis, median times to progression and median survivals were similar for both groups. Poor and good risk partial responders had similar survivals. Twelve percent of CMF patients treated with Adriamycin at the time of progression had partial responses with an associated improved survival. Since CMF is as effective as CAMF, but has less toxicity, low dose therapy with CMF is more acceptable than CAMF as an initial chemotherapy regimen for metastatic breast cancer. Adriamycin may be reserved for subsequent regression induction.", "Three combination chemotherapy regimens each with or without the methanol-extracted residue of bacillus Calmette-Guérin (BCG) (MER) were compared for efficacy. After stratification for disease-free interval and dominant sites of disease, patients were randomized to either CMF (cyclophosphamide [CYC], 100 mg/m2 orally, days 1 through 14; methotrexate [MTX], 40 mg intravenously [IV], days 1 and 8; 5-fluorouracil [5-FU], 500 mg/m2 IV, days 1 and 8), or CAF (CYC, 100 mg/m2 orally, days 1 through 14; doxorubicin [DOX], 25 mg/m2 IV, days 1 and 8; 5-FU, 500 mg/m2 IV, days 1 and 8), or CAFVP (CAF as above plus vincristine [VCR], 1.0 mg/m2 IV, days 1 and 8; and prednisone [PRED], 40 mg/m2 orally, days 1 through 14). Nonspecific immunotherapy with MER was administered in five sites at 100 micrograms or at the lowest tenfold dilution that produced a 1-cm indurated lesion. A total of 432 patients were entered, but 37 were disqualified, leaving 395 evaluable for treatment results and toxicities. One hundred thirty-five evaluable patients were randomized to chemoimmunotherapy until October 28, 1978. One hundred twenty-six evaluable patients were randomized to chemotherapy alone in the same time period. For the entire study, a total of 260 evaluable patients were randomized to chemotherapy. Chemoimmunotherapy patients were compared with the initial 126 chemotherapy patients. Chemotherapy regimens were compared among all 260 patients. Patient characteristics were similar between regimens and between chemotherapy and chemoimmunotherapy treatment groups. For patients on chemotherapy plus MER, there was no significant differences between the regimens for response frequencies: 43%, 41%, and 32%, respectively for CMF, CAF, and CAFVP. The comparable chemotherapy alone group had 36%, 58%, and 63% response, respectively. The response rates, adjusted for chemotherapy regimen, were 52% and 38% (P = .02) for chemotherapy and chemoimmunotherapy, respectively. MER was associated with painful ulcers and fevers. Thus, MER produced toxicity without response or survival benefit and further randomization after October 28, 1978 was to chemotherapy alone. For 260 evaluable patients on chemotherapy alone, the complete (CR) and partial responses (PR) were 37%, 55%, and 58%, respectively for CMF, CAF, and CAFVP. These response rates for CAF and CAFVP were significantly better than CMF (P = .01 and P less than .01, respectively). These comparisons were consistent within subgroupings such as dominant sites of disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "One hundred fifty-five eligible women with metastatic breast cancer were randomly allocated to receive monthly cycles of either CMFP (cyclophosphamide, methotrexate, 5-fluorouracil, prednisone) or CAF (cyclophosphamide, doxorubicin, 5-fluorouracil), and 12 patients were studied to evaluate the effects of additional Corynebacterium parvum immunotherapy. Overall response rates of 53% were seen with CMFP and CAF. CAF was associated with significantly more complete responses than CMFP (17% v 5%). However, CAF therapy was administered for eight months and CMFP for six months. Only 13% of the CAF patients had a complete response during the first six months of chemotherapy, and this was not significantly different from the complete response rate on CMFP. The median response durations (CMFP, 6.3 months; CAF, 11.0 months), times to treatment failure (CMFP, 5.7 months; CAF, 7.8 months), and survival times (CMFP, 15.8 months; CAF, 18.6 months) were not statistically different. Other investigators who have compared CAF to CMF-containing regimens have reported a large advantage in CAF therapy among patients with \"good risk\" sites of metastases (local-regional recurrence, bone, lung nodules). Such a finding was not confirmed by our study: in multivariate analyses the groups associated with an advantage for CAF tended to have a poorer prognosis than the groups associated with an advantage for CMFP. There was significantly more nausea and vomiting after CAF treatment, and CMFP treatment was associated with significantly more edema, Cushingoid features, fever, and eye symptoms.", "Ninety-four patients were entered in a clinical trial assessing the clinical activity of cyclophosphamide, doxorubicin, and prednisone (CAP) versus a combination of cyclophosphamide. 5-Fluorouracil, and prednisone (CFP) in patients with advanced breast cancer. Objective response rates were comparable, 49% for CFP and 46% for CAP. There was no statistical difference between the duration of response of the two regimens or in time to progression. Most importantly, survival differences were not apparent. Both regimens were clinically tolerable and toxicities, for the most part, were comparable. Thus, no therapeutic advantage existed for either of these polychemotherapy regimens in patients with advanced breast cancer.", "A prospective study with two cytotoxic combinations (cyclophosphamide, methotrexate, and fluorouracil (CMF), and adriamycin plus vincristine (AV)) was carried out in 110 patients with advanced breast cancer. There was no significant difference between the treatment groups in the response rate after primary treatment, the median duration of response, and the median survival. In both groups responders survived for longer than non-responders. Secondary treatment after crossover for progression or relapse resulted in response rates of 35% for AV and 20% for CMF. Toxicity was mainly represented by reversible haemosuppression. These results are comparable with those obtained with other multiple-drug regimens, and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer.", "To evaluate the substitution of methotrexate with doxorubicin (Dox) in CMF-(cyclophosphamide, methotrexate, 5-fluorouracil) containing regimen for advanced breast cancer, 415 postmenopausal patients below the age of 66 years, naïve to chemotherapy, were accrued from 1980 to 1984 and followed-up until 1995. They received tamoxifen 30 mg daily orally and by randomisation either 400 mg/m2, cyclophosphamide, 25 mg/m2 doxorubicin and 500 mg/m2 5-fluorouracil (CAF) or 40 mg/m2 methotrexate instead of Dox (CMF) intravenously (i.v.) days 1 + 8 repeated every 4 weeks. Dox was substituted by methotrexate at a cumulative dose of 550 mg/m2. Among 341 eligible patients the response rate and median time to progression was significantly in favour of CAF: 53% CAF versus 36% CMF (P = 0.002) and 11.8 months CAF versus 6.5 months CMF (P = 0.001). Median duration of response was 19.5 CAF versus 18.0 CMF months, and survival 20.8 CAF versus 17.4 CMF months (non-significant). The two regimens were equimyelotoxic. There were no treatment-related fatalities but 1 patient with congestive heart failure on CAF was reported. Nausea/vomiting, stomatitis and infections were modest in both groups, whilst alopecia was more common with CAF. Regression analysis showed that long recurrence free interval, good performance status, and no visceral involvement was significantly related to long-term survival, whilst the treatment regimen was not. It is concluded that in chemotherapy-naïve patients with advanced breast cancer Dox-containing regimens are superior and remain the first choice of chemotherapy, especially in patients with visceral metastases, until newer drugs and combinations have been proven to be superior.", "Patients with advanced breast carcinoma and no prior chemotherapy were prospectively evaluated to assess the induction capabilities of cyclophosphamide, methotrexate and 5-fluorouracil (CMF), Adriamycin and vincristine (AV), and CMF plus prednisone (CMFP). The crossover responsiveness from CMF or CMFP to AV and of AV to CMF were also assessed. A disproportionate randomization led to 166 analyzable cases on AV, 79 on CMF were also assessed. A disproportionate randomization led to 166 analyzable cases on AV, 79 on CMF and 86 on CMFP induction. One hundred and twelve patients were evaluated on crossover. Induction response rates were similar with 56% on AV, 57% on CMF and 63% on CMFP. Crossover response rates ranged from 32% to 41%. CMFP and AV were superior to CMF in terms of response duration (P = 0.05), and CMFP was superior to either in terms of time to treatment failure (P = 0.04), and survival (P = 0.03). Treatment failures occurred in only the on-study organ sites of disease in 73% of the patients and did not appear to be related to the response achieved. CMF was associated with more thrombocytopenia than either AV or CMFP (P = 0.03). AV was associated with fewer infections than CMFP (P = 0.02), less diarrhea than CMFP (P = 0.04), more emesis than CMF (P = 0.02), and more neurologic toxicity than either CMF or CMFP (P less than 0.0001). There was also more emesis with CMF than with CMFP (P = 0.006). CMFP was associated with greater delivery of CMF than was the CMF regimen despite a similar day 1 leukocyte distribution. These results strongly suggest that CMF(P) and AV are clinically noncross-resistant regimens, that AV and CMF are essentially equivalently active induction regimens, and that CMFP is superior to CMF and AV.", "Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer.", "The prospective controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination (CAP), compared with the combination including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFVP), in untreated metastatic breast cancer. One hundred and twenty-three patients (greater than 2 cycles) were evaluated: 61 on the CAP, and 62 on the CMFVP schedule. An objective response (CR + PR) to CAP combination chemotherapy was achieved in 72% of patients (43/61), with a high rate (36%) of complete remissions. In terms of metastatic site, the response rate appeared to be particularly high in soft tissue and visceral organ (lung, liver) metastases. In the CMFVP group, an objective response was noted in 26 of 62 patients (42%), with 16% complete remissions. The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen (P less than 0.01). The duration of remissions was 6-28 + months (means = 14) for the CAP, and 4-15 + months (mean = 9) for the CMFVP schedule. Toxic side effects were more pronounced in the CAP group, particularly myelosuppression, with anemia prevailing. Side effects of CMFVP treatment were moderate. In 39 CMFVP previously treated cases, CAP was administered as second-line treatment, and an objective response was observed in 51% of cases (20/39). Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer.", "nan", "Adriamycin is of noteworthy efficacy in the treatment of metastatic breast cancer. Its role in combination regimens is under investigation. One hundred seventy-five women with advanced breast cancer were entered into a prospectively randomized trial comparing two five-drug regimens. Regimen CMFVP consisted of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), vincristine (V), and prednisone (P). Regimen CAFVP was identical but substituted Adriamycin (A) for methotrexate. Twenty-seven patients were disqualified; 148 were evaluable. With CMFVP the complete response rate (CR) was 11%, and the partial response rate (PR) was 46%; with CAFVP, CR was 13% and PR was 45%. Duration of response tended to be slightly longer for patients on the Adriamycin arm. The median survival for CR and PR patients with CMFVP was 20.2 months, which was shorter (p = .07) than the 33 month median survival with CAFVP. Although statistical significance was not reached at the 5% level, the increased survival of responders on the Adriamycin regimen supports the data of other studies which suggest that first line combination chemotherapy in advanced breast cancer should include Adriamycin.", "Previous Phase II studies using the combination of mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) in the treatment of metastatic breast carcinoma have shown this regimen to be active and well tolerated. In this randomized Phase II study, the authors compared the NFL regimen with a standard CMF regimen in the first-line therapy of patients with metastatic breast carcinoma.\n One hundred twenty-eight women receiving their first chemotherapy for metastatic breast carcinoma were entered into this randomized study. Sixty-four patients were treated with NFL: mitoxantrone 12 mg/m2 IV on Day 1; leucovorin 300 mg IV over 30-60 minutes on Days 1, 2, and 3, immediately preceding administration of 5-fluorouracil; and 5-fluorouracil 350 mg/m2 IV bolus on Days 1, 2, and 3. Sixty-four patients received CMF: cyclophosphamide 600 mg/m2 IV on Day 1; methotrexate 40 mg/m2 IV on Day 1; and 5-fluorouracil 600 mg/m2 IV on Day 1. Both regimens were repeated at 21-day intervals; responding patients received at least 8 courses.\n Patients treated with NFL had a higher response rate than patients treated with the CMF regimen (45% vs. 26%, respectively; P = 0.021). Median duration of response was 9 months with NFL and 6 months with CMF (P = 0.10); 11 patients had long responses (>12 months) with NFL versus 4 patients with CMF (P = 0.06). Median survival was similar for both groups. Both regimens were well tolerated, with infrequent Grade 3 or 4 toxicities.\n NFL is an active, well-tolerated regimen for the treatment of metastatic breast carcinoma; it produced a higher response rate than the CMF regimen used in this study. Although more intense CMF regimens or regimens containing doxorubicin would likely increase the response rate, they would almost certainly do so with the consequence of greater toxicity as compared with NFL. NFL is an excellent initial palliative treatment option for elderly patients or patients who have exhibited poor tolerance for other chemotherapy regimens.", "nan", "In 126 postmenopausal women with metastatic breast cancer, four chemotherapeutic combination programs were tested. Patients were stratified and randomized to one of the four programs: (1) fluorouracil, cytoxan and prednisone (CFP): (2) fluorouracil, cytoxan and Adriamycin (CAF); (3) cytoxan and Adriamycin (CA); or (4) alternating combinations of CFP-CA. Objective response rates were 17% for 18 patients on CFP, 25% for 40 patients on CAF, 42% for 41 patients on CA and 63% for 19 patients on CFP-CA. CFP-CA provided a significantly higher response rate than either CFP or CAF. The response rate of CA was intermediate. The duration of remission and survival were similar for all four groups. When progression or relapse following remission was demonstrated, patients were rerandomized to either adrenalectomy or tamoxifen. There were no responders either in the 15 patients undergoing adrenalectomy or the 11 patients receiving tamoxifen. In a crossover study, nine adrenalectomized patients received tamoxifen and four tamoxifen-treated patients underwent adrenalectomy. None responded. It appears that response rates to hormonal modalities are reduced in patients previously treated by combination chemotherapy.", "In January, 1972, the Southwest Oncology Group initiated two randomized studies for patients with advanced breast cancer. The study for patients with prior chemotherapy showed a 33% response rate with adriamycin. The study for patients without previous chemotherapy consisted of three treatment regimens; a weekly repeated combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone; these same five drugs given in courses of 5 days repeated every 4 weeks; and adriamycin as a single agent every 3 weeks. For the 283 evaluable patients, the response rates were: weekly combination 63/106 (59%); intermittent combination 39/98 (40%); and adriamycin 31/79 (39%). The median duration of response was 8 months for weekly combination, 10 months for intermittent therapy and only 4 months for adriamycin. Leukopenia was the dose-limiting toxicity with all three regimens. The weekly combination is the most effective therapy for patients with advanced disease. Extensive trails of combinations that include adriamycin are underway.", "One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m(-2) day 1 and 8 i.v., 5-fluorouracil 600 mg m(-2) day 1 and 8 i.v., methotrexate 40 mg m(-2) day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m(-2), mitoxantrone 6.5 mg m(-2), both i.v. day 1 3-weekly for 8 cycles) as first line treatment with chemotherapy. Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who received MM; 95% confidence interval for difference in response rates (-1%-29%), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.001) and alopecia (P < 0.001) and fewer dose reductions and delays in patients randomized to MM. No statistically significant differences were seen between the two regimes in terms of quality of life (QOL). However, some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment. Despite the fact that results surrounding response rates and time to progression did not reach statistical significance, their possible compatibility with an improved outcome on CMF treatment must be borne in mind. However, MM is a well-tolerated regimen with fewer side-effects than CMF, which with careful patient management and follow-up, therefore, may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly.", "Two intensive chemotherapy regimens CFPMV (Cytoxan [cyclophosphamide], 5-fluorouracil, prednisone, methotrexate, vincristine) and CA (Cytoxan, Adriamycin [doxorubicin]) were tested against a moderate regimen, CFP, in a prospective three-arm, randomized study with crossover when relapse or failure occurred, in order to assess whether the response, duration of remission, and survival can be altered by using more intensive regimens as first-line or as rescue therapy. All three regimens were equally effective as initial chemotherapy: CFP 26/46 (57%); CFPMV 31/48 (65%) and CA 26/47 (55%) (P = 0.61) with the least toxicity for the CFP regimen. Median duration of remission were 9.5, 11, and 9 months, respectively. Complete responses were almost identical in all three regimens: 4/46 (9%); 6/48 (12%) and 5/47 (11%) (P = 0.94). CFPMV was an effective regimen as second-line therapy: 11/33 (33%) or third-line therapy: 7/21 (33%). The CA regimen was equally effective as second-line therapy: 8/25 (32%), suggesting that intensive regimens provide an effective rescue therapy, as well in previous responders as in nonresponders. Initial intensive regimens have not substantially altered long-term survival in the whole group of treated patients, Arm II (CFPMV----CA----CFP) 17.6 months; Arm III (CA----CFP----CFPMV) 12.3 months when compared with initial moderate regimens Arm I (CFP----CFPMV----CA) 16.6 months (P = 0.24). The same lack of difference in survival was noticed in responder patients in each arm: Arm II 19.0 months; Arm III 16.0 months versus Arm I 22.0 months (P = 0.13). Our data suggest that a moderate regimen is as effective as more intense regimens for induction therapy in metastatic breast cancer, with less toxicity, preserving the opportunity for an effective rescue therapy with intensive regimens in second or third-line chemotherapy.", "To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer.\n Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles.\n A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF.\n This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer." ]

[ "10679534", "18061648", "11256551", "16440537" ]

[ "Asthma education and quality of life in the community: a randomised controlled study to evaluate the impact on white European and Indian subcontinent ethnic groups from socioeconomically deprived areas in Birmingham, UK.", "Reducing asthma health disparities in poor Puerto Rican children: the effectiveness of a culturally tailored family intervention.", "Feasibility of a nurse-run asthma education program for urban African-Americans: a pilot study.", "A culturally competent asthma management intervention: a randomized controlled pilot study." ]

[ "Whether asthma morbidity in minority groups can be reduced by preventative health care measures delivered in the relevant ethnic dialects requires further evaluation. This study reports clinical outcomes and quality of life from a community based project investigating white European (W/E) and Indian subcontinent (ISC) ethnic groups with asthma living in deprived inner city areas of Birmingham, UK.\n Six hundred and eighty nine asthmatic subjects (345 W/E, 344 ISC) of mean (SD) age 34.5 (15) years (range 11-59) and mean forced expiratory volume in one second (FEV(1)) of 80% predicted were interviewed in English, Punjabi, Hindi, or Urdu. Subjects randomised to the active limb of a prospective, open, randomised, controlled, parallel group, 12 month follow up study underwent individually based asthma education and optimisation of drug therapy with four monthly follow up (active intervention). Control groups were seen only at the beginning and end of the study. Urgent or emergency interactions with primary and secondary health care (clinical outcomes) and both cross sectional and longitudinal data from an Asthma Quality of Life Questionnaire (AQLQ) were analysed.\n Clinical outcomes were available for 593 subjects. Fewer of the active intervention group consulted their GP (41.8% versus 57.8%, odds ratio (OR) 0.52 (95% CI 0.37 to 0.74)) or were prescribed antibiotics (34.9% versus 51.2%, OR 0.51 (95% CI 0.36 to 0.72)), but by ethnicity statistically significant changes occurred only in the W/E group with fewer also attending A&E departments and requiring urgent home visits. Active intervention reduced the number of hospital admissions (10 versus 30), GP consultations (341 versus 476), prescriptions of rescue oral steroids (92 versus 177), and antibiotics (220 versus 340), but again significant improvements by ethnicity only occurred in the active W/E group. AQLQ scores were negatively skewed to the higher values; regression analysis showed that lower values were associated with ISC ethnicity. Longitudinal changes (for 522 subjects) in the mean AQLQ scores were small but statistically significant for both ethnic groups, with scores improving in the active and worsening in the control groups.\n Active intervention only improved clinical outcomes in the W/E group. AQLQ scores, although lower in the ISC group, were improved by active intervention in both ethnic groups.", "Island and mainland Puerto Rican children have the highest rates of asthma and asthma morbidity of any ethnic group in the United States.\n We evaluated the effectiveness of a culturally adapted family asthma management intervention called CALMA (an acronym of the Spanish for \"Take Control, Empower Yourself and Achieve Management of Asthma\") in reducing asthma morbidity in poor Puerto Rican children with asthma.\n Low-income children with persistent asthma were selected from a national health plan insurance claims database by using a computerized algorithm. After baseline, families were randomly assigned to either the intervention or a control group.\n No significant differences between control and intervention group were found for the primary outcome of symptom-free days. However, children in the CALMA intervention group had 6.5% more symptom-free nights, were 3 times more likely to have their asthma under control, and were less likely to visit the emergency department and be hospitalized as compared to the control group. Caregivers receiving CALMA were significantly less likely to feel helpless, frustrated, or upset because of their child's asthma and more likely to feel confident to manage their child's asthma.\n A home-based asthma intervention program tailored to the cultural needs of low income Puerto Rican families is a promising intervention for reducing asthma morbidity.", "The objective of the study was to assess the feasibility of implementing and evaluating a culturally appropriate in-patient asthma education program specifically targeted for African-Americans. A consecutive sample of 28 African-American patients ages 18-50 who were hospitalized for asthma were randomized to an intervention group, which received three one-on-one sessions on chronic asthma management, or a control group, which received the usual care. Data on symptom frequency, self-management behaviors, quality of life, depression, and health care resource use were collected at baseline and at 3 and 6 months. Although the time required to recruit our sample took longer than anticipated, 28 subjects agreed to be in the study (70% acceptance rate) and complete the baseline interview. We observed no statistically significant differences from baseline or changing trends in frequency of asthma symptoms, self-management behaviors, and health care resource use between the intervention and control groups at 3 and 6 months. However patients in the intervention group demonstrated a greater average increase in asthma-related quality of life and a greater average decrease in depression than the control group. Feasibility issues included shortened length of stay, which necessitated conducting all three self-management sessions together; multiple interruptions during the sessions, and retention issues at 3- and 6-month follow-ups. The lessons learned from this pilot study are invaluable in that they will enable us to make changes in our existing protocol to ensure the success of a larger clinical trial.", "Despite significant medical advances, many ethnic and racial minority children who live in inner cities continue to experience disproportionately high levels of asthma morbidity and mortality compared with white children. As a result, a growing number of psychosocial asthma management interventions are being developed to address their needs; however, only a few of these interventions have incorporated cultural variables into their treatments and have had their efficacy evaluated.\n To examine the efficacy of the Multifamily Asthma Group Treatment (MFAGT), designed to enhance asthma management and reduce emergency department (ED) visits among African American and Hispanic families.\n Twenty-four African American and Hispanic families who have children with asthma were randomly assigned to either the MFAGT or the Standard Psychoeducational Asthma Intervention. Differences in the number of ED visits and the level of asthma management in both groups were compared 1 year before and 1 year after the intervention. In addition, these groups were contrasted to a control group that did not receive any psychoeducational intervention.\n The MFAGT was significantly (P = .04) more effective than the Standard Psychoeducational Asthma Intervention and the control in decreasing ED visits and increasing parental asthma knowledge.\n These preliminary results suggest that the MFAGT is efficacious in enhancing asthma management and in reducing ED visits in inner-city African American and Hispanic children from a lower socioeconomic background." ]

[ "12583822", "11155831", "12701945", "11072941" ]

[ "How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study.", "What should be included in meta-analyses? An exploration of methodological issues using the ISPOT meta-analyses.", "Publication bias and meta-analyses: a practical example.", "Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?" ]

[ "nan", "To explore the impact of methodologic issues on the results of meta-analyses. The following issues were examined: the type of literature search strategy used; inclusion or exclusion of non-peer-reviewed studies; the inclusion or exclusion of non-English language publications; the effect of trial quality; and the inclusion or exclusion of non-placebo-controlled studies.\n The International Study of Perioperative Transfusion (ISPOT) meta-analyses were used to evaluate each of the methodologic issues. The 10 meta-analyses consisted of technologies to reduce the need for perioperative red blood cell transfusion. The number of trials for each of the meta-analyses varied from 2 to 45. Both EMBASE and MEDLINE searches were conducted, including the use of systematic search strategies.\n MEDLINE identified the vast majority of trials. Alone, MEDLINE would have missed 8 studies compared to 10 for EMBASE. Use of the systematic search strategies greatly reduced the number of articles to be reviewed compared to open searches. Type of publication, country of study origin, inclusion of non-English publications, and trial quality had very little impact on the estimates of effect. The use of placebo versus open-label control affected the magnitude of the odds ratio for two of the meta-analyses. The results of the two meta-analyses were not statistically significant if only placebo-controlled trials were included.\n While methodologic issues had very little impact on the ISPOT meta-analyses, further studies are needed in a variety of other clinical settings. Because MEDLINE, coupled with a review of the references in the identified trials, identified the vast majority of trials, one needs to consider the costs and benefits of searching EMBASE and the pursuance of unpublished and unindexed trials.", "Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the \"gray+literature.\" However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.\n We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.\n The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.\n We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them.", "The inclusion of only a subset of all available evidence in a meta-analysis may introduce biases and threaten its validity; this is particularly likely if the subset of included studies differ from those not included, which may be the case for published and grey literature (unpublished studies, with limited distribution). We set out to examine whether exclusion of grey literature, compared with its inclusion in meta-analysis, provides different estimates of the effectiveness of interventions assessed in randomised trials.\n From a random sample of 135 meta-analyses, we identified and retrieved 33 publications that included both grey and published primary studies. The 33 publications contributed 41 separate meta-analyses from several disease areas. General characteristics of the meta-analyses and associated studies and outcome data at the trial level were collected. We explored the effects of the inclusion of grey literature on the quantitative results using logistic-regression analyses.\n 33% of the meta-analyses were found to include some form of grey literature. The grey literature, when included, accounts for between 4.5% and 75% of the studies in a meta-analysis. On average, published work, compared with grey literature, yielded significantly larger estimates of the intervention effect by 15% (ratio of odds ratios=1.15 [95% CI 1.04-1.28]). Excluding abstracts from the analysis further compounded the exaggeration (1.33 [1.10-1.60]).\n The exclusion of grey literature from meta-analyses can lead to exaggerated estimates of intervention effectiveness. In general, meta-analysts should attempt to identify, retrieve, and include all reports, grey and published, that meet predefined inclusion criteria." ]

[ "9354192", "16696804", "15479682", "21453880" ]

[ "Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis.", "Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.", "Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine.", "A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis." ]

[ "Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non-pathogenic E. coli.\n A total of 120 patients with inactive ulcerative colitis were included in a double-blind, double-dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse-free times and global assessment.\n The start and end scores of the CAI demonstrated no significant difference (P = 0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse-free time of 103 +/- 4 days for mesalazine and 106 +/- 5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported.\n From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.", "Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder.\n To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis.\n 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission.\n Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05).\n Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.", "Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis.\n In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses.\n The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different.\n The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.", "To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) to maintain remission in patients with ulcerative colitis.\n Patients with left-sided ulcerative colitis in remission - including proctitis and at least one relapse within the last year were randomised (2:1) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks. The patients were evaluated clinically, endoscopically and histologically at entry and if relapsing. No other medication for ulcerative colitis than the study drug was allowed during the study. Primary endpoint was maintenance of clinical remission, secondary endpoints comparisons of days to relapse, and safety and tolerability of the study drug. The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients.\n Thirty-two patients were randomised. Twenty patients received Probio-Tec AB-25 and twelve patients received placebo. Five patients (25%) in the Probio-Tec AB-25 group and one patient (8%) in the placebo group maintained remission after 1 year of treatment (p=0.37). The median time to relapse was 125.5days (range 11-391 days) in the probiotic group and 104 days (range 28-369 days) in the placebo group respectively, (p=0.683). Probio-Tec AB-25 was overall well tolerated.\n In this small randomised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis. A difference may be achieved in larger studies, but the clinical significance of this would be questionable. This study was registered in ClinicalTrial.gov (NCT00268164).\n Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved." ]

[ "12021952", "8302340", "8676624" ]

[ "A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis.", "A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group.", "Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II." ]

[ "Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis. This report describes a placebo-controlled, double-blind randomised clinical trial of riluzole carried out in ALS patients with advanced stage disease or aged over 75 years. The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel. Another goal was to assess the safety of riluzole in patients with advanced-stage disease. One hundred and sixty-eight patients were included, randomised to either riluzole 50 mg b. i. d. or to placebo, and treated for eighteen months. Riluzole was well-tolerated in this patient population, and the adverse events observed were similar in nature and frequency to those observed in previously published clinical trials in patients included in pivotal trials. The study could not include enough patients to reach adequate power to detect differences in survival between the two treatment groups, and no such difference was in fact observed. In conclusion, riluzole is well-tolerated in ALS patients with advanced stage disease.", "Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment. Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis.\n To evaluate the efficacy and safety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole was 100 mg per day. Randomization was stratified according to the site of disease onset (the bulbar region or the limbs). The primary end points were survival and rates of change in functional status. The main secondary end point was change in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median follow-up, 573 days).\n After 12 months, 45 of 78 patients (58 percent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group (P = 0.014). For patients with bulbar-onset disease, one-year survival rates were 35 percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P = 0.014), whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent, respectively (P = 0.17). The survival advantage with riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of 77] with riluzole) at the end of the placebo-controlled period, but it remained significant in the overall population (P = 0.046) as well as in the patients with bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013). The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group (P = 0.028). Adverse reactions to riluzole included asthenia, spasticity, and mild elevations in aminotransferase levels. Twenty-seven patients in the riluzole group withdrew from the study, as compared with 17 in the placebo group.\n The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset.", "Amyotrophic lateral sclerosis (ALS) is a progressive disease with no effective treatment. In an initial study, riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients. We have carried out a double-blind, placebo-controlled, multicentre study to confirm those findings and to assess drug efficacy at different doses.\n 959 patients with clinically probable or definite ALS of less than 5 years' duration were randomly assigned treatment with placebo or 50 mg, 100 mg, or 200 mg riluzole daily; randomisation was stratified by centre and site of disease onset (bulbar or limb). The primary outcome was survival without a tracheostomy. Secondary outcomes were rates of change in functional measures (muscle strength, functional status, respiratory function, patient's assessments of fasciculation, cramps, stiffness, and tiredness). The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat. Drug-effect on survival was assessed before (log-rank test) and after adjustment for known prognostic factors (Cox's model).\n At the end of the study, after median follow-up of 18 months, 122 (50.4%) placebo-treated patients and 134 (56.8%) of those who received 100 mg/day riluzole were alive without tracheostomy (unadjusted risk 0.79, p = 0.076; adjusted risk 0.65, p = 0.002). In the groups receiving 50 mg and 200 mg riluzole daily, 131 (55.3%) and 141 (57.8%) patients were alive without tracheostomy (relative to placebo 50 mg adjusted risk 0.76, p = 0.04; 200 mg 0.61, p = 0.0004). There was a significant inverse dose response in risk of death. No functional scale discriminated between the treatment groups. The most common adverse reactions were asthenia, dizziness, gastrointestinal disorders, and rises in liver enzyme activities; they were commonest with the 200 mg dose.\n Overall, efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio. This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS." ]

[ "11341669", "11148527", "7717738" ]

[ "Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment.", "Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children.", "Double blind placebo controlled trial of pizotifen syrup in the treatment of abdominal migraine." ]

[ "To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind, placebo-controlled trial of famotidine. Global and quantitative pain assessments were done before and after each treatment period. The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components. Based on the global evaluation, there was a clear benefit of famotidine over placebo (68% vs 12%). Using the quantitative assessment, however, the mean improvement of the score using famotidine versus placebo was not statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant improvement in this score during the first treatment period regardless of medication used (period effect: P = 0.05). A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objectively using the derived score. However, famotidine is significantly more effective than placebo among children with peptic symptoms. The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy.", "In a randomized, double-blind controlled trial, 42 children with irritable bowel syndrome (IBS) were given pH-dependent, enteric-coated peppermint oil capsules or placebo. After 2 weeks, 75% of those receiving peppermint oil had reduced severity of pain associated with IBS. Peppermint oil may be used as a therapeutic agent during the symptomatic phase of IBS.", "Fourteen children with abdominal migraine were treated with pizotifen and placebo in a double blind crossover trial. The results showed pizotifen to be clearly superior to placebo in the prophylaxis of abdominal migraine. The importance of clearly distinguishing abdominal migraine from other forms of recurrent abdominal pain is emphasised." ]

[ "6987043", "1467292" ]

[ "Discoid lupus erythematosus. Diagnostic features and evaluation of topical corticosteroid therapy.", "Treatment of cutaneous lupus erythematosus with acitretin and hydroxychloroquine." ]

[ "nan", "A randomized, double-blind, multicentre study was performed to compare the efficacy of acitretin (50 mg/day) with hydroxychloroquine (400 mg/day) in 28 and 30 patients, respectively, suffering from cutaneous lupus erythematosus (LE). The study was carried out over an 8-week period. Improvement of facial LE lesions after treatment with acitretin and hydroxychloroquine was assessed using several clinical parameters. In the acitretin group there was marked improvement or clearing of erythema in 10/24 patients (42%), of infiltration in 15/24 (63%) and of scaling/hyperkeratosis in 12/20 (60%). In the hydroxychloroquine group there was complete clearing or marked improvement of erythema in 17/25 patients (68%), of infiltration in 17/25 (68%) and of scaling/hyperkeratosis in 15/23 (65%). Overall improvement occurred in 13/28 patients (46%) treated with acitretin and in 15/30 patients (50%) with hydroxychloroquine. The incidence of side-effects was higher in the acitretin group, and necessitated discontinuation of treatment in four patients. The present results demonstrate that both acitretin and hydroxychloroquine provide effective treatment in approximately 50% of cases of cutaneous LE." ]

[ "16618912" ]

[ "Temperature-controlled radiofrequency treatment of tonsillar hypertrophy for reduction of upper airway obstruction in pediatric patients." ]

[ "To determine if temperature-controlled radiofrequency (TCRF) tonsil reduction and adenoidectomy (TCRF&A) and conventional tonsillectomy and adenoidectomy (T&A) are statistically similar in outcome and to compare morbidity between TCRF&A and conventional T&A.\n Randomized control trial.\n Tertiary care children's hospital.\n The study population comprised 23 patients aged 2.6 to 12.5 years with symptoms of obstructive sleep apnea, hypertrophic tonsils with no other areas of upper airway obstruction with the exception of hypertrophic adenoids, and a body mass index (calculated as weight in kilograms divided by the square of height in meters) of less than 30.\n Temperature-controlled radiofrequency tonsil reduction (mean +/- SD, 12.6 +/- 1.5 ablations per patient and 994.68 +/- 91.88 J per insertion) and adenoidectomy or traditional bovie T&A.\n Primary outcomes were respiratory distress index and total volume reduction. Secondary outcomes include postoperative pain, daytime sleepiness, speech and swallowing problems, weight and diet, narcotic use, and analogue snoring scale.\n The respiratory distress index difference for TCRF&A was 5.63 vs 6.56 for standard T&A. On postoperative day 1 for the 13 patients who underwent TCRF&A, 0 reported severe pain, 11 (85%) had mild to moderate pain, and 2 (15%) had no pain. In the 10 patients who underwent standard T&A, 1 (10%) had severe pain and 9 (90%) had mild to moderate pain. By postoperative week 1, all TCRF&A patients experienced mild or no pain, whereas 1 (10%) of the standard T&A patients still had moderate pain. Mean visual analogue snore scores (0-10) 4 weeks after surgery were less than 1 for both groups. The mean +/- SD weight loss at postoperative week 1 for TCRF tonsil reduction patients was 1.0 +/- 3.5 lb (0.45 +/- 1.58 kg) vs 4.6 +/- 3.9 lb (2.07 +/- 1.76 kg) for standard T&A patients. Return to normal diet at postoperative week 1 occurred in 11 TCRF&A patients (85%) and 0 standard T&A patients.\n The respiratory distress indexes were similar for TCRF&A patients and standard T&A patients. In addition, there were similar analog snoring scales, decreased pain, and weight loss." ]

[ "3046657", "8093742", "2694314" ]

[ "Effect of single-dose ivermectin therapy on human Onchocerca volvulus infection with onchocercal ocular involvement.", "Reduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis.", "Ophthalmological results from a placebo controlled comparative 3-dose ivermectin study in the treatment of onchocerciasis." ]

[ "Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects.", "The safety and efficacy of ivermectin in the prevention of blindness from onchocerciasis have been established in many studies that have addressed the drug's effects on the front of the eye. We undertook a study with sufficient statistical power to detect an effect on optic nerve disease (OND), probably the main cause of blindness in the disorder. The trial was based in 34 mesoendemic communities in Kaduna State, Nigeria. Villagers aged 5 years and older were randomly assigned annual dosing with ivermectin or placebo for 3 years. Participants underwent medical and ophthalmological examinations before the first, third, and fourth treatments. 3522 villagers aged 15 and older were re-examined at least once. Skin-snip samples were taken at baseline for calculation of microfilarial load. The outcome measure was development of disc pallor accompanied by objective evidence of deterioration in visual function; 116 subjects (45 ivermectin-treated, 71 placebo-treated) showed such changes during the trial. The incidence rate ratio (ivermectin vs placebo) was 0.90 (95% CI 0.54-1.51) for subjects with loads of 0-10 mf (microfilariae) per mg skin and 0.52 (0.29-0.93) for subjects with more than 10 mf/mg. The incidence rate ratio varied little when account was taken of age, sex, presence of pre-existing disc pallor in one eye, previous use of diethylcarbamazine citrate, or doses of ivermectin or placebo received. There was evidence that ivermectin reduced the incidence of OND in subjects with microfilarial loads above 10 mf/mg but had little effect in those with lower loads. Sustained annual delivery of ivermectin could prevent a substantial proportion of onchocercal blindness in mesoendemic communities.", "One hundred and ninety eight patients with moderate to heavy infection with Onchocerca volvulus and with eye involvement in most, were allocated randomly to treatment with 100, 150 or 200 mcg/kg body weight of ivermectin or placebo given as a single oral dose in a double-blind dose finding study. The patients were drawn from an area under over ten years of vector control in Northern Ghana by the Onchocerciasis Control Programme, OCP. They underwent detailed clinical, laboratory and ophthalmological examination before treatment and in the review period of one year in hospital. Ivermectin given in a dose of 100, 150 or 200 mcg/kg eliminated microfilariae similarly slowly over 3-6 months and was associated with inflammatory reaction in the anterior segment which resolved without treatment. No changes in the fundus of the eye was detected by fluorescein angiography and no no-table other adverse eye reaction was observed. The ceiling of therapeutic activity of ivermectin in the eye is therefore put at 100 mcg/kg which is lower than the level fo 150 mcg/kg found in the skin. The apparent discrepancy may be due to different dose requirements on account of different mechanisms of action of ivermectin at the two sites. In the skin there is active killing while in the eye it is presumed there is a passive elimination of microfilariae." ]

[ "12694427", "12789968", "15794454", "8794967", "17274236" ]

[ "Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis. A dual-center, double-blind placebo-controlled study.", "The effect of four mouthrinses on oral malodor.", "Use of a novel group of oral malodor measurements to evaluate an anti-oral malodor mouthrinse (TriOralTM) in humans.", "Efficacy of a 2-phase oil: water mouthrinse in controlling oral malodor, gingivitis, and plaque.", "Effects of herbal mouthwash containing the pericarp extract of Garcinia mangostana L on halitosis, plaque and papillary bleeding index." ]

[ "The aim of this double-blind, parallel study was to test the clinical efficacy of a newly developed mouthrinse in the treatment of oral halitosis in patients without periodontitis.\n Forty volunteers, recruited in two centers, participated in this study. Patients were selected on the basis of (1) halitosis of oral origin, (2) full-mouth organoleptic score>1, using an arbitrary 0-5 scale, (3) level of volatile sulfur compounds (VSC)>170 parts per billion (ppb) and (4) Winkel tongue coating index (WTCI)>4 (0-12). Intervention included gargling with a mouthrinse containing chlorhexidine (0.05%), cetylpyridinium chloride (0.05%) and zinc-lactate (0.14%) or with a placebo mouthrinse without active ingredients. At days 0 and 14 clinical variables were assessed in order of performance: (1) organoleptic assessments, (2) levels of VSC, and (3) WTCI.\n Treatment with the active mouthrinse resulted in a significant mean reduction in the organoleptic score from 2.8 to 1.5 (p<0.005). In the placebo group, no significant reduction in the mean organoleptic score occurred. Consequently, this resulted, after 2 weeks, in a greater change of the organoleptic scores in the test group in comparison to the placebo group (p<0.005). The mean VSC scores were reduced from 292 to 172 ppb in the test group (p<0.005), whereas no reduction was observed in the placebo group. At the 2-week examination, the mean change of the VSC scores in the test group was significantly greater than the mean change in the placebo group (p<0.005). Neither in the test nor in the placebo group a significant reduction in tongue coating was observed.\n In conclusion, the tested mouthrinse is effective in the treatment of oral halitosis.", "The purpose of the study was to compare the efficacy of four mouthrinses in clinical outcomes of changes in oral malodor measurements in a 4-week, randomized, double-blind, longitudinal clinical trial in adults. The four rinses were coded as Products 1, 2, 3, and 4 so that neither the examiners nor subjects had the knowledge of treatment. Of the four mouthrinses, two were commercially available mouthrinses with essential oils (EO) or chlorine dioxide plus zinc (CD/Zn) as active ingredients (Products 1 and 4), one mouthrinse was a formulation containing cetylpyridinium chloride (Product 2), and one was a placebo (Product 3). A total of 99 subjects who met the study criteria were assigned randomly to one of the four groups. At three separate visits (0, 2, and 4 weeks), subjects received an examination of the oral soft tissues and were assessed for baseline oral malodor by two organoleptic judges and a laboratory instrument that measures oral malodor. Subjects were instructed to use the assigned rinse, and the measurements were performed again after 2 and 4 hours. Throughout the 4-week study period, each subject was asked to use the assigned rinse twice daily per the manufacturer's recommended directions. The results showed that the four mouthrinses reduced oral malodor within 4 hours after a single usage, with Product 2 being the most effective and the placebo being the least effective. Daily use of EO, CD/Zn, and placebo rinses for up to 4 weeks did not reduce oral malodor from week 0 baseline values, and the effects on oral malodor were comparable among these three mouthrinses. Product 2 was the only mouthrinse that reduced oral malodor from baseline values after 2 and 4 weeks of daily use.", "This study compared the ability of a test mouthwash containing zinc chloride and sodium chlorite (TriOral) to reduce intrinsic oral malodor, to that of two other mouthrinses, one with zinc chloride only and the other with no zinc chloride/no sodium chlorite, using a novel group of oral malodor parameter measurements.\n Forty-eight subjects completed the study; 16 in the test group, 17 in the zinc only group, and 15 in the no zinc chloride/ no sodium chlorite group. At baseline and after two and four weeks, parameters assessed were 1) malodorants in the headspace of and in solution in resting whole saliva determined organoleptically, 2) breath volatile sulfur compounds (VSC) measured with a sulfide monitor (Halimeter), 3) fresh and incubated saliva oxidation-reduction potential (E(h)) measured with a platinum electrode, and 4) level of saliva indolic compounds (IC), indole and skatole, determined colorimetrically with Kovac's reagent. The VSC, E(h), and IC data for the three mouthrinses were analyzed statistically by repeated measures ANOVA between groups, and by 2-way ANOVA within groups. Corresponding organoleptic data were analyzed by Kruskal-Wallis and Friedman non-parametric tests.\n Organoleptic, VSC, and E(h) evaluations clearly showed the zinc chloride/sodium chlorite test mouthrinse to be more effective than the other two rinses. In all cases, the level of significance was p < 0.001 between the test mouthrinse and its no zinc chloride/no sodium chlorite control; between test mouthrinse and the zinc chloride only product, significance was p < 0.05, < 0.001 and < 0.01 for the organoleptic, VSC, and E(h) tests, respectively. Noteworthy was the observation that the mean organoleptic saliva headspace score with the test mouthrinse was reduced to zero, and VSC levels fell below 50 ppb S by the end of the study, a level where the breath is usually non-odorous. The test mouthwash also appeared more effective in reducing the salivary IC levels, but the results did not reach significance at p < 0.05 unless IC levels were amplified in the saliva by incubation overnight at 37 degrees C. Correlations between the various procedures were highly significant, achieving in almost all cases a probability level of p < 0.001.\n The results supported the conclusion that the zinc chloride plus sodium chlorite mouthrinse (TriOral) is more effective in reducing oral malodor than a zinc chloride alone mouthrinse, and even more effective than its no zinc chloride/no sodium chlorite mouthrinse control. The methods used in this study were consistent with one another, and highly effective in measuring various parameters that characterize oral malodor.", "The purpose of the study was to examine the anti-malodor, anti-gingivitis, and plaque reducing properties of a 2 phase oil:water mouthrinse compared with a control mouthrinse. Fifty subjects rinsed with one of the two rinses for 30 seconds twice a day over 6 weeks, while continuing their normal oral hygiene habits. Measurements were made at time zero (prior to beginning the rinsing regimen), and > or = 9 hours following rinsing, at intervals of 1, 3, and 6 weeks. Malodor of whole mouth, as well as tongue dorsum anterior and posterior, was assessed on a 0 to 5 semi-integer scale by two odor judges. Volatile sulphide compounds (VSC) were determined using a sulphide monitor. Gingival, plaque, and bleeding indices were recorded for Ramfjord teeth. Oral microbial levels were assessed using the oratest. Salivary levels of diamines (putrescine and cadaverine) were analyzed by HPLC. Results were analyzed by 2-tailed covariant ANOVA, with the time zero value as covariant. Dramatic improvements were observed in parameters associated with malodor, periodontal health, plaque accumulation, and microbial levels in both groups. As compared to time zero scores, whole mouth odor, tongue dorsum anterior and posterior odors decreased continuously over time, attaining 80%, 79% and 70%, reductions, respectively following 6 weeks, in the 2-phase mouthrinse group, versus 70%, 77% and 59% for the control group. For whole mouth and tongue dorsum posterior, the reductions observed in the 2-phase mouthrinse group were significantly greater than those obtained with the control mouthrinse (P = 0.026 and P = 0.025, respectively), suggesting that the 2-phase mouthrinse is superior to the control mouthrinse in long-term reduction of oral malodor. For bleeding index, gingival index, oral microbial levels, and VSC, differences between the groups were not significant. Diamine levels were not significantly reduced in either group. The control mouthrinse reduced plaque index more significantly than the 2-phase mouthrinse (P < 0.005). The results of this randomized clinical trial suggest that the 2-phase oil:water mouthrinse formulation is superior to the control mouthrinse in long-term reduction of oral malodor.", "To determine the effects of herbal mouthwash containing the pericarp extract of Carcinia mangostana L on volatile sulfur compound (VSC) levels, plaque index (PI) and papillary bleeding index (PBI) in gingivitis subjects and the recurrence of these parameters after periodontal treatment.\n Sixty subjects who were diagnosed as having mild or moderate chronic gingivitis were randomly distributed into herbal or placebo mouthwash groups. On day 1, all parameters were recorded. Subjects rinsed with the assigned mouthwash and VSC was measured at 30 min and 3 h post-rinsing. For the following 2 weeks, subjects practiced their usual oral hygiene and rinsed with the assigned mouthwash twice daily after tooth brushing. On day 15, parameters were recorded. In the 4-week washout period that followed, subjects received scaling and polishing. After another baseline examination, they were re-randomized into the herbal or placebo group and rinsed with mouthwash for 2 weeks. All parameters were re-evaluated on day 15.\n All parameters were significantly different compared to baseline in both groups at 30 min, 3 h and day 15 (p < 0.05). When compared between groups, VSC was significantly different at day 15 (p < 0.05). After scaling, poloshing and rinsing with mouthwash for 2 weeks, PI and PBI were significantly different compared to baseline (p < 0.05) while VSC was not (p > 0.05). When compared between groups, VSC was significantly different (p < 0.05).\n Herbal mouthwash containing the pericarp extract of G. mangostana may be used as an adjunct in treating oral malodor." ]

[ "8296357", "9593358", "12749486", "11555433" ]

[ "Bed nets for the prevention of malaria and anaemia in pregnancy.", "A community randomized controlled trial of insecticide-treated bednets for the prevention of malaria and anaemia among primigravid women on the Kenyan coast.", "Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya.", "The impact of insecticide-treated bednets on malaria and anaemia in pregnancy in Kassena-Nankana district, Ghana: a randomized controlled trial." ]

[ "A prospective comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border. Women in 3 adjacent study sites were allocated at random to receive either a single size permethrin-impregnated bed net (PIB), a non-impregnated bed net (NIB), or to a control group who used either their own family size non-impregnated bed net (FNIB) or no net. In one study site, but not the other 2, PIB significantly reduced parasite densities and, together with FNIB, reduced the incidence of malaria in pregnancy from 56% to 33% (relative risk = 1.67, confidence interval = 1.07-2.61, P = 0.03, allowing for parity). Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates. The incidence of anaemia (haematocrit < 30%) at all study sites was significantly lower at delivery in the PIB (27%) and FNIB groups (21%) than in the NIB group (41%) or those using no net (56%). This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent. Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight. Infant mortality was high (16%) and strongly associated with prematurity, low birth weight and maternal anaemia. PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development. Although the overall effect of bed nets on patent parasitaemia was marginal, they were associated with a significant reduction in maternal malaria-associated anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effectiveness of insecticide-treated bednets (ITBN) in preventing malaria and anaemia among primigravidae living in Kilifi District, Kenya, was assessed by a randomized controlled trial between September 1994 and November 1995. All residents within 28 community clusters received ITBN in July 1993, whilst residents of another 28 clusters served as contemporaneous controls. All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment. 503 primigravidae were recruited. 91.4% were anaemic antenatally (Hb < 11 g/dl): 91.0% from the intervention arm and 92.0% from the control arm. Severe anaemia (Hb < 7 g/dl) was found among 15.1% of intervention women and 20.1% of control women (P = 0.28). No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups. In the women delivering in hospital (n = 130), there was no association between placental malaria infection and the intervention: 77.4% of placentas from control women had evidence of past or active infection, compared with 72.0% of placentas from intervention women (P = 0.76). Similarly, in the women delivering in hospital, ITBN did not improve birth weight, and there were no differences in perinatal mortality between the two study groups. Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting, there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae. Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast.", "The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data on birth outcome were available on 2,754 (89.6%) of 3,072 deliveries. Women (n = 780) were followed monthly throughout pregnancy in 19 of 79 villages. Among gravidae 1-4, ITNs were associated with reductions of 38% (95% confidence interval [CI] = 17-54%) in the incidence of malaria parasitemia and 47% (95% CI = 6-71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI = 0.01-1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI = 20-47%), and the prevalence of low birth weight was reduced by 28% (95% CI = 2-47%) in gravidae 1-4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.", "The impact of insecticide-treated bednet use on malaria and anaemia in pregnancy was assessed, as a supplementary study, in a major WHO/TDR-supported bednet trial in northern Ghana between July 1994 and April 1995. The study area was divided into 96 clusters of compounds, with 48 clusters being randomly allocated to intervention. All pregnant women were included in the study but the focus was on primigravidae and secundigravidae. 1961 pregnant women were recruited into the study--1033 (52.7%) in the treated bednet group and 928 (47.3%) in the no net group. 1806 (92.1%) had blood taken for malaria microscopy and haemoglobin determination in the third trimester. Pregnancy outcomes were reported for 847 women. The characteristics of women in intervention and control groups were comparable. The odds ratios, with 95% confidence interval (CI), for different study endpoints were, for Plasmodium falciparum parasitaemia--0.89 (0.73, 1.08), for anaemia--0.88 (0.70, 1.09), for low birthweight (LBW)--0.87 (0.63, 1.19), indicating no benefit for treated bednet use. Effective net use by parity varied from 42% in primigravidae to 63% in multigravidae, in spite of free nets and insecticide impregnation. The main reasons for not using a net were warm weather and perceived absence of mosquito biting. Chloroquine use in pregnancy was low and comparable in both groups. Implications of findings for malaria control in pregnancy and further research are discussed." ]

[ "16616167", "12731685", "16392976", "8929935", "16675163", "12003113", "17366252", "17018819", "8678182", "9718104", "9849771", "16897413" ]

[ "Treatment barriers identified by substance abusers assessed at a centralized intake unit.", "Case management for substance abusers with HIV/AIDS: a randomized clinical trial.", "Randomized trial of drug abuse treatment-linkage strategies.", "Effective services for homeless substance abusers.", "The effectiveness of outreach case management in re-enrolling discharged methadone patients.", "Impact of centralized intake on case management services.", "Treatment entry and predictors among opiate-using injection drug users.", "Effectiveness of intensive case management for substance-dependent women receiving temporary assistance for needy families.", "Efficacy of enhanced outreach counseling to reenroll high-risk drug users 1 year after discharge from treatment.", "Outcome of a controlled trial of the effectiveness of intensive case management for chronic public inebriates.", "Predicting postprimary treatment services and drug use outcome: a multivariate analysis.", "Treating homeless clients with severe mental illness and substance use disorders: costs and outcomes." ]

[ "The 59-item Barriers to Treatment Inventory (BTI) was administered to 312 substance abusers at a centralized intake unit following assessment but before treatment entry to assess their views on barriers to treatment. Factor analysis identified 25 items in 7 well-defined latent constructs: Absence of Problem, Negative Social Support, Fear of Treatment, Privacy Concerns, Time Conflict, Poor Treatment Availability, and Admission Difficulty. The factorial structure of the barriers is consistent with the findings of other studies that asked substance abusers about barriers to treatment and is conceptually compatible with Andersen's model of health care utilization. Factors were moderately to highly correlated, suggesting that they interact with one another. Selected characteristics were generally not predictive of barrier factors. Overall, results indicate that the BTI has good content validity and is a reliable instrument for assessing barriers to drug treatment. The potential utility of the BTI in assessment settings is discussed.", "In a random assignment study, substance-abusing patients with HIV/AIDS in a public general hospital received a brief contact condition or received 12 months of case management delivered by paraprofessionals. Patient outcomes included substance use, HIV transmission risk, physical health, psychological status, and quality of living situation. In both conditions, a significant decrease occurred in a range of problems from Intake to the 6-month interview, followed by no significant pattern of change at 12- and 18-month interviews. On major outcome variables, there were no significant differences between the brief contact and case management conditions. Sixteen percent had died by the 18-month interview. Process data indicated wide variation in the amount of case management received by participants, and the amount of case management was not related to improvement in the outcome measures. The study has limitations yet does not support the hypothesis that case management improves outcomes better than brief contact for this population.", "A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6 months. MMT enrollment at 3 months was 47% (case management), 89% (voucher), 93% (case management plus voucher), and 11% (usual care); at 6 months enrollment was 48%, 68%, 79%, and 21%, respectively. Case management and vouchers can be valuable in health settings to link substance abusers with medical problems to drug abuse treatment.", "A heterogeneous and representative sample of 323 homeless individuals in the metropolitan-Denver area with alcohol or other substance abuse problems received a comprehensive array of substance-abuse treatment services. Following treatment, these individuals showed dramatic improvement on average in their (a) levels of alcohol and drug use, (b) housing status, (c) physical and mental health, (d) employment, and (e) quality of life. Those who received more service improved more than those who received less service. These improvements are attributable, at least partly, to the treatment rather than to alternative hypotheses such as spontaneous remission. However, the rate of improvement generally slowed during the six-month follow-up period. A random half of the clients received intensive case management in addition to the other services. Case management marginally increased clients' contacts with addictions counselors, but had little effect on the level of other services received or on the tailoring of services to client needs. As a result, case management also had little, if any, effect on outcomes.", "Heroin dependence is a chronic relapsing disease often requiring multiple treatment experiences. Despite this knowledge, few methadone programs follow-up with discharged patients who frequently continue to engage in risky behaviors. The aim of this project was to evaluate the effectiveness of outreach case management for post-discharged methadone patients.\n At 90 days post-discharge 128 active out of treatment heroin users were randomly assigned to receive either a passive referral (PR) for drug treatment (n=52) or were provided with 6 weeks of outreach case management (OCM), an intervention designed to help motivate and coach patients to re-enter treatment (n=76).\n At 6 months post-baseline 29% of the OCM participants had successfully re-enrolled in drug treatment compared to 8% of the PR participants (chi(2)=7.6, d.f.=1, p=0.006). A logistic regression analysis showed that OCM participants were nearly six times more likely than PR participants to re-engage in MMT (OR=5.8, CI=1.6-20.8, p=0.008). Moreover, OCM subjects had fewer opiate and cocaine positive urines at the 6-month follow-up compared to PR subjects.\n The findings highlight the importance of engaging former patients in treatment and actively assisting in treatment re-entry. OCM is a simple approach to reduce the number of out-of-treatment drug users, although availability of treatment funding limits enrollment opportunities.", "The Chicago Target Cities demonstration project was designed to improve the effectiveness and accessibility of substance abuse treatment in large metropolitan areas. The primary interventions included centralized intake (CIU), comprehensive standardized assessment procedures, and management of a centralized wait list. A part of this project, the effectiveness of a case management model implemented through the CIU, was tested. Participants were randomly assigned to one of two conditions, case management (CM) or no case management (No-CM). The primary objectives of the CIU case management model were to improve the show rate to treatment, provide referrals to ancillary services, and to support treatment completion. Participants in both groups could also receive other support services provided by staff for the treatment agencies. CM participants were significantly more likely to show to treatment (78.9%) than No-CM participants (71.8%). Case management was found to primarily improve the show rates for younger participants, who without CM were significantly less likely to show for treatment than older participants. CM participants were significantly more likely to receive referrals to non substance abuse treatment services than No-CM participants, although the number of referrals was low in both conditions. No differences were found in the amount or length of substance abuse treatment services received by participants in the two conditions.", "This study examines entry into drug treatment among 491 street-recruited injection drug users in Denver, Colorado. The primary outcome was treatment entry within 6 months. Univariate tests were run using chi-square t-test analyses. Significant variables were included in a multiple logistic regression. Results showed that having more outreach contacts, not being homeless, having fewer problems with alcohol but more problems with drugs, and the contemplation or determination stage of change were associated with entering treatment. The identification of predictors of treatment entry may be useful for treatment centers in engaging certain populations of drug users. Behavioral interventions are an important tool in recruiting drug injectors into treatment.", "We tested the effectiveness of a long-term coordinated care strategy--intensive case management (ICM)--compared with usual care (UC) among a group of substance-dependent women receiving Temporary Assistance for Needy Families (TANF).\n Substance-dependent women on TANF (N=302) were recruited from welfare offices. They were assessed and randomly assigned to ICM or UC; follow-up was at 3, 9, and 15 months. UC consisted of a health assessment at the welfare office and a referral to substance abuse treatment and TANF services. ICM clients received ICM services in addition to UC services.\n ICM clients had significantly higher levels of substance abuse treatment initiation, engagement, and retention compared with UC clients. In some cases, ICM treatment attendance rates were double those of UC rates. Additionally, almost twice as many ICM clients were abstinent at the 15 month follow-up compared with UC clients (P<.0025).\n ICM is a promising intervention for managing the chronic nature of substance dependence among women receiving TANF. Future research should refine long-term care strategies-such as ICM-that address the chronic nature of substance dependence among low-income populations.", "Because discharged methadone maintenance patients represent a population at particularly high public health risk, the authors studied such patients 1 year after their discharge from a methadone program.\n The locations of 94 of 110 discharged patients were successfully determined 1 year after discharge. Nine (10%) of these patients had died, 37 (39%) were already reenrolled in treatment, and 7 (7%) did not require treatment. The 41 remaining subjects were randomly assigned to either the enhanced outreach counseling condition (N = 27) or a standard referral condition (N = 14).\n Within 2 weeks following this intervention, 17 (63%) of the 27 patients in the enhanced outreach counseling program and one (7%) of the 14 patients not in the program had reenrolled in treatment.\n These data suggest that enhanced outreach counseling may be an effective outreach strategy as well as a risk-reduction for discharged methadone maintenance patients.", "The objective of this study was to test whether an intensive case management intervention would be effective with a group of homeless chronic public inebriate clients. The primary goals of the case management were to improve the financial and residential stability of the clients and to reduce their use of alcohol.\n Subjects (N = 298, 81% male) were interviewed at baseline, randomly assigned to treatment and control conditions and given follow-up interviews at 6-month intervals for 2 years. Case management services were provided for the duration of the project. Follow-up rates for the first three interviews averaged 82%.\n Repeated measures MANCOVAs showed significant group differences favoring the case-managed group in all three areas targeted by the intervention: total income from public sources, nights spent in \"own place\" out of the previous 60 nights and days drinking out of the previous 30 days. The results held whether the three variables were analyzed jointly or separately and for alternative measures of drinking and homelessness. Although statistically significant, the group differences are generally not large.\n The results indicate that case management had a beneficial effect on the clients receiving it. This effect may have been the result of an increase in services received by the case-managed clients.", "The substance abuse treatment field is continually challenged to develop interventions that encourage drug abusers to remain longer in therapeutic services and that facilitate improved outcomes. As one of those interventions, case management has generally not been subjected to multivariate analysis to evaluate its role in accomplishing those goals. Using a sample of 444 veterans who received substance abuse treatment services, this study examines relationships among demographic and psychosocial variables at intake, assignment to either traditional or enhanced (case management) treatment services, and both proximal (postprimary treatment contact) and distal (severity of drug use) measures of outcome. Multivariate analyses reveal that case-managed clients stay longer in postprimary treatment services than non-case-managed clients, and consequently, longer postprimary treatment contact leads to better drug use outcomes. The implications of these findings are discussed.", "This study compared the costs and outcomes associated with three treatment programs that served 149 individuals with dual disorders (i.e., individuals with co-occurring severe mental illness and substance use disorders) who were homeless at baseline. The three treatment programs were: Integrated Assertive Community Treatment (IACT), Assertive Community Treatment only (ACTO), and standard care (Control). Participants were randomly assigned to treatment and followed for a period of 24 months. Clients in the IACT and ACTO programs were more satisfied with their treatment program and reported more days in stable housing than clients in the Control condition. There were no significant differences between treatment groups on psychiatric symptoms and substance use. The average total costs associated with the IACT and Control conditions were significantly less than the average total costs for the ACTO condition." ]

[ "14575968", "12738722" ]

[ "Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial.", "Multicenter randomized Phase II study of paclitaxel (1-hour infusion), fluorouracil, hydroxyurea, and concomitant twice daily radiation with or without erythropoietin for advanced head and neck cancer." ]

[ "Anaemia is associated with poor cancer control, particularly in patients undergoing radiotherapy. We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer.\n We did a multicentre, double-blind, randomised, placebo-controlled trial in 351 patients (haemoglobin <120 g/L in women or <130 g/L in men) with carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received curative radiotherapy at 60 Gy for completely (R0) and histologically incomplete (R1) resected disease, or 70 Gy for macroscopically incompletely resected (R2) advanced disease (T3, T4, or nodal involvement) or for primary definitive treatment. All patients were assigned to subcutaneous placebo (n=171) or epoetin beta 300 IU/kg (n=180) three times weekly, from 10-14 days before and continuing throughout radiotherapy. The primary endpoint was locoregional progression-free survival. We assessed also time to locoregional progression and survival. Analysis was by intention to treat.\n 148 (82%) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L (women) or 150 g/L (men) compared with 26 (15%) given placebo. However, locoregional progression-free survival was poorer with epoetin beta than with placebo (adjusted relative risk 1.62 [95% CI 1.22-2.14]; p=0.0008). For locoregional progression the relative risk was 1.69 (1.16-2.47, p=0.007) and for survival was 1.39 (1.05-1.84, p=0.02).\n Epoetin beta corrects anaemia but does not improve cancer control or survival. Disease control might even be impaired. Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials.", "To expand on our experience with the combination of paclitaxel, fluorouracil, hydroxyurea, and twice daily irradiation (T-FHX) and to assess the impact of weekly administration of erythropoietin (r-HuEpo) on transfusion requirements, we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and randomized patients to receive weekly doses of r-HuEpo.\n A total of 90 patients with locally advanced head and neck cancers (stage IV, 96%; N(2)/N(3), 66%) were treated on a regimen of 1-h infusion of paclitaxel (100 mg/m(2)/day, day 1), 120-h infusion of 5-fluorouracil (600 mg/m(2)/day, days 0-5); hydroxyurea 500 mg p.o. every 12 h for 11 doses; and radiation 150cGy bid, days 1-5 of each 14-day cycle repeated for five cycles over 10 weeks (7200-7500 cGy). Before initiating therapy, patients were randomized to receive r-HuEpo 40,000 IU s.c. once weekly.\n At median follow-up of 40 months, 3-year progression-free survival is 62%, locoregional control is 84%, and systemic control is 79%. Overall survival is 59%. Anemia, leucopenia, dermatitis, and mucositis were the most frequent grade 3 or 4 toxicities. Patients randomized to erythropoietin experienced less grade 2/3 anemia (52 versus 77%; P = 0.02), but transfusion requirements were not significantly different.\n T-FHX is an active and tolerable regimen inducing local tumor control and promising survival with organ preservation in high-risk patients. One h infusion of paclitaxel simplified the regimen without compromising efficacy. Addition of erythropoietin does not reduce the need for transfusion with this nonplatinum-containing regimen. T-FHX should be advanced to a randomized trial and compared with a cisplatin-based concomitant regimen." ]

[ "7131544", "8655662", "3908674" ]

[ "The effects of ultrasound examination on maternal anxiety levels.", "The effect of the amount of feedback on anxiety levels during ultrasound scanning.", "Impact of fetal testing on maternal anxiety." ]

[ "A study has been conducted to assess the psychological effects of real-time ultrasound on the pregnant woman's attitudes and anxiety levels. A consecutive series of primiparae, fulfilling the selection criteria of obstetrically \"low risk,\" was assigned at random to two conditions of ultrasound, namely, (a) high feedback (N = 67), where the woman saw the moving fetus in utero; and (b) low feedback (N = 62), where the monitor screen was not visible and no specific feedback was provided. A third group of women was assessed following a wait period in order to compare state anxiety levels among the three groups. Attitude assessments showed consistent preultrasound-post-ultrasound change, with more uniformly positive attitudes displayed by the high-feedback group. No between-group differences in state anxiety emerged as a result of ultrasound compared with a wait control period. No differences emerged with respect to anticipatory anxiety measures. The results are considered in the context of evidence on the importance of psychological state on the course and outcome of pregnancy. It is suggested that the low-risk characteristics of this sample may have precluded effects on anxiety and it is concluded that the therapeutic potential of ultrasound warrants further study.", "This study examined the influence of different levels of feedback and of other situational and buffering variables on the psychological effects of ultrasound examinations of 211 pregnant women. The patients were randomly assigned to two different experimental conditions: high feedback and low feedback. The subjects' levels of anxiety (both trait- and state-anxiety) were measured immediately before and after the ultrasound examination. Overall, there was a significant decrease in the level of state-anxiety, which could not be explained by the different levels of feedback provided. Situational and buffering variables were not found to be related to the degree of psychological benefit produced by the scan.", "We evaluated the impact of fetal testing on maternal anxiety. A consecutive series of high-risk women attending during the third trimester for fetal assessment were each randomly assigned to one of four conditions: (1) high-feedback ultrasonography (n = 11), in which the monitor screen was visible; (2) low-feedback ultrasonography (n = 8), in which specific visual and verbal feedback was denied; (3) fetal heart rate monitoring (n = 11); or (4) a video control (n = 7), in which the women viewed a videotape of an ultrasonographic recording. Assessments were conducted before and after each procedure. No change was found in attitude ratings towards the fetus, although there was a significant reduction in state anxiety from before to after, with the reduction most pronounced in women undergoing high-feedback ultrasonography." ]

[ "10989464", "3035479", "10595816", "7749764", "8259853", "9348595", "10087313", "10779814", "8983284", "11902300", "7492164", "2661789", "231736", "10380232", "17372773", "10533454", "519355", "3701526", "3013104", "15202162", "10532104", "7833098", "3522818", "10370357", "7844684", "8772908" ]

[ "A comparison of oral ondansetron syrup or intravenous ondansetron loading dose regimens given in combination with dexamethasone for the prevention of nausea and emesis in pediatric and adolescent patients receiving moderately/highly emetogenic chemotherapy.", "Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial.", "A prospective randomized trial of the anti-emetic efficacy of ondansetron and granisetron during bone marrow transplantation.", "Randomized double-blind crossover ondansetron-dexamethasone versus ondansetron-placebo study for the treatment of chemotherapy-induced nausea and vomiting in pediatric patients with malignancies.", "[Antiemetic efficacy of granisetron in pediatric cancer treatment--(2). Comparison of granisetron and granisetron plus methylprednisolone as antiemetic prophylaxis].", "Controlling conditioning-related emesis in children undergoing bone marrow transplantation.", "Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study.", "[Oral granisetron solution as prophylaxis for chemotherapy-induced emesis in children: double-blind study of 2 doses].", "An increased loading dose of ondansetron: a north european, double-blind randomised study in children, comparing 5 mg/m2 with 10 mg/m2.", "Randomized, double-blind, crossover, placebo-controlled trial of intravenous ondansetron for the prevention of intrathecal chemotherapy-induced vomiting in children.", "Randomised comparison of ondansetron and metoclopramide plus dexamethasone for chemotherapy induced emesis.", "Antiemetic therapy for chemotherapy-induced vomiting: metoclopramide, benztropine, dexamethasone, and lorazepam regimen compared with chlorpromazine alone.", "Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol.", "Cost-effectiveness analysis of tropisetron vs. chlorpromazine-dexamethasone in the control of acute emesis induced by highly emetogenic chemotherapy in children.", "A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy.", "A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy.", "Domperidone or metoclopramide in preventing chemotherapeutically induced nausea and vomiting.", "Methylprednisolone for chemotherapy-induced emesis: a double-blind randomized trial in children.", "Nabilone: an alternative antiemetic for cancer chemotherapy.", "Single-dose oral granisetron versus multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia.", "[Evaluation of the anti-emetic effectiveness of two drug formulations of Ondansetron in combined chemotherapy for children with malignant tumors].", "Safety, tolerability, efficacy and plasma concentrations of tropisetron after administration at five dose levels to children receiving cancer chemotherapy.", "Antiemetics in children receiving cancer chemotherapy: a double-blind prospective randomized study comparing metoclopramide with chlorpromazine.", "Randomized double-blind comparison of single high-dose ondansetron and multiple standard-dose ondansetron in chemotherapy-naive pediatric oncology patients.", "A randomized comparison of intravenously administered granisetron versus chlorpromazine plus dexamethasone in the prevention of ifosfamide-induced emesis in children.", "Comparison of dexamethasone and metoclopramide as antiemetics in children receiving cancer chemotherapy." ]

[ "This double-blind, parallel-group, multicenter study compared the efficacy and safety of intravenous (i.v.) ondansetron with oral syrup ondansetron plus oral dexamethasone in the prevention of nausea and emesis in pediatric patients receiving moderately/highly emetogenic chemotherapy. On each day of chemotherapy, patients were administered ondansetron 5 mg/m2 i.v. and placebo syrup orally (n = 215) or ondansetron 8 mg syrup orally and placebo i.v. (n = 223) plus dexamethasone 2-4 mg p.o. Ondansetron 4 mg syrup p.o. was administered twice daily for 2 days following the cessation of chemotherapy. Complete or major control of emesis was obtained in 89% patients in the i.v. group and 88% patients in the oral syrup group during the worst day of chemotherapy treatment (90% CI: -6, 4) and in 85% and 82% patients, respectively, during the worst day of the study period (90% CI: -8, 3). Intravenous or oral syrup ondansetron plus dexamethasone was well tolerated and effective in preventing chemotherapy-induced emesis in pediatric patients.", "In a randomized, double-blind, crossover trial, nabilone was compared to prochlorperazine for control of cancer chemotherapy-induced emesis in 30 children 3.5 to 17.8 years of age. All subjects received two consecutive identical cycles of chemotherapy with the trial antiemetics given in accordance to a body weight-based dosage schedule beginning eight to 12 hours before treatment. The overall rate of improvement of retching and emesis was 70% during the nabilone and 30% during the prochlorperazine treatment cycles (P = .003, chi 2 test). On completion of the trial, 66% of the children stated that they preferred nabilone, 17% preferred prochlorperazine, and 17% had no preference (P = .015, chi 2 test). Major side effects (dizziness, drowsiness, and mood alteration) were more common (11% v 3%) during the nabilone treatment cycles. CNS side effects appeared to be dose related and were most likely to occur when the nabilone dosage exceeded 60 micrograms/kg/d, but individual tolerance to nabilone varied considerably. Lower dosages of nabilone were associated with equivalent efficacy and no major side effects. Nabilone appears to be a safe, effective, and well-tolerated antiemetic drug for children receiving cancer chemotherapy. Although major side effects may occur at higher dosages, nabilone is preferable to prochlorperazine because of improved efficacy.", "To determine the comparative anti-emetic efficacy of ondansetron and granisetron in patients undergoing bone marrow transplantation, we performed a double-blind, randomized trial in pediatric and adult patients receiving transplants at the University of Minnesota. The results in 187 patients stratified by age (<18 years, n = 51; > or =18 years, n = 136) were analyzed. The average number of emetic episodes in the entire group from day -7 to 2 was 0.86/day for patients receiving ondansetron and 0.73/day for those receiving granisetron (p = 0.32). No differences were noted between the two drugs in total days of complete or major control of emesis or in the number of requests for additional drugs to alleviate symptoms of nausea. The use of total-body irradiation-containing conditioning regimens was associated with a decreased number of emetic episodes compared with regimens of chemotherapy alone. Perceived nausea was evaluated using a nausea scoring system, and no differences were apparent between the granisetron and ondansetron groups; however, reported nausea was significantly higher in females (p<0.01) and in the adult population (p = 0.05). We conclude that both ondansetron and granisetron provide good control of nausea and vomiting experienced with conditioning regimens for bone marrow transplantation. The relative cost of the drugs within an institution must be considered in developing standard anti-emetic regimens for bone marrow transplantation.", "To determine whether the addition of dexamethasone to ondansetron (OND + DEX) is a more effective antiemetic regimen than ondansetron (OND) alone in children receiving chemotherapy.\n Children who had solid tumors and who were receiving highly emetogenic chemotherapy, including cisplatin, carboplatin, cyclophosphamide, and ifosfamide, were randomized (1:1) in a double-blind fashion to receive either OND 0.15 mg/kg intravenously (i.v.) 30 min before and 4 and 8 h after chemotherapy and placebo, or OND + DEX (same OND doses plus DEX 8 mg/m2 i.v. 30 min before chemotherapy, followed by 16 mg/m2 in divided doses) as antiemetics. The patients were crossed over to the other antiemetic regimen when receiving an identical course of chemotherapy. Patients were monitored for emetic episodes, nausea, appetite, sense of well-being, and antiemetic adverse events.\n A total of 33 patients were evaluated. Sixty-one percent of the patients receiving OND + DEX regimens had a complete response for emetic episodes as compared with 23% with OND alone. Combined complete and major responses (two or less emetic episodes) were 86% for OND + DEX and 67% for OND. Failure for emetic episodes (more than five vomitings/day) were seen only in 7-10% of the total population. Minimal or no nausea was experienced in 74% of OND + DEX courses and in 52% of the OND courses. Appetite was better in OND + DEX courses (p = 0.006). Both antiemetic arms had similar adverse events. Mild to moderate sedation occurred in about half of the courses, followed by restlessness (29%), headache (17%), diarrhea (17%), and hiccups (2%).\n The combination of ondansetron and dexamethasone is superior to ondansetron alone to control emetic episodes in children receiving highly emetogenic chemotherapy (p = 0.04).", "A crossover clinical trial was carried out to compare the effectiveness and safety of granisetron alone (40 micrograms/kg) with that from a combination of granisetron plus methylprednisolone (MPL, 10 mg/kg) for control of emesis and vomiting induced by anticancer drugs in children with cancer. Complete control of emesis and vomiting were achieved in 95% (19/20 cases) of patients receiving the combination compared to 85% (17/20 cases) of patients receiving granisetron alone. There were no clinical toxicities or side effects in either treatment group. These data indicated that the combination of granisetron plus MPL was superior for control of emesis and vomiting in children receiving cytostatic anticancer drugs.", "To compare the efficacy of two antiemetic regimens, ondansetron alone versus perphenazine with diphenhydramine, on emesis control in children undergoing conditioning therapy for bone marrow transplantation (BMT).\n Single-center, prospective, open, randomized, crossover study.\n Pediatric BMT unit in an urban area in the northeastern United States.\n 28 children, ages 4-17, undergoing BMT for a variety of underlying diseases.\n After randomization to one of the two antiemetic regimens, emesis control was evaluated during conditioning therapy. If a participant experienced more than five episodes of emesis during any 12-hour period, he or she was crossed over to the other antiemetic regimen. If emesis control still was not achieved, the participant was removed from the study and other medications were administered to control vomiting.\n Number of emetic episodes and incidence of side effects.\n 10 of 15 patients (67%) who received ondansetron experienced major emesis control (no more than two episodes) compared with 0 of 13 patients (0%) who received perphenazine with diphenhydramine (p = 0.044, Fisher exact test). Of those who crossed over to ondansetron after failure with perphenazine and diphenhydramine, 38% were able to achieve major emesis control.\n Ondansetron offers superior antiemetic control over the combination of perphenazine and diphenhydramine for children undergoing high-dose chemotherapy with or without total body irradiation for BMT.\n Oncology nurses must develop an understanding of the etiology of therapy-induced emesis and the mechanisms of action of the various classes of antiemetic agents designed to control it. Implementing documentation to describe events of emesis will help to tailor antiemetic therapy to a patient's specific situation. Further research is necessary to determine alternate strategies, including different combinations or sequences of antiemetics to provide optimum emetic control during acute and delayed phases of emesis. The higher cost of ondansetron therapy must be considered within the context of superior efficacy.", "The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.", "This multicentric double-blind, dose-ranging study was to compare efficacy and safety of two oral doses of granisetron solution in the prevention of chemotherapy-induced emesis in children with malignant diseases : 294 children, aged 1 to 16, treated with a moderately or highly emetogenic chemotherapy were randomly assigned to receive oral granisetron either 20 microg/kg (n = 143) or 40 microg/kg (n = 151) before and 6 to 12 hours after the start of chemotherapy. Fifty-one percent of patients treated with 20 microg/kg bd of oral granisetron solution achieved a complete response (no vomiting, no worse than mild nausea, no rescue therapy and no withdrawal during the specified period) and 59% achieved a major response (no more than one episode of vomiting, no worse than mild nausea, no rescue therapy and no withdrawal during the specified period). There was no difference between the two oral doses of granisetron. Treatment was rated as good or very good by investigators in 70% of cases. In conclusion, oral granisetron suspension either at 20 microg/kg bd or at 40 microg/kg bd showed good efficacy and safety in the prevention of chemotherapy-induced emesis in children with malignant diseases. Oral granisetron solution can be used as prophylaxis of emesis in children receiving moderately or highly emetogenic chemotherapy.", "A North European, randomised, double-blind study, comparing a loading-dose of ondansetron of 5 mg/m2 with 10 mg/m2, administered intravenously before highly emetogenic chemotherapy, was carried out in 187 chemotherapy-naïve children. In the first 24 h, both groups received further ondansetron intravenously at a dose of 5 mg/m2 8-hourly. Thereafter, ondansetron was given at an oral dose of 4 or 8 mg depending on the surface area of the child, three times a day and continued for at least 3 days after the last day of chemotherapy. There was no difference in the control of emesis between the two groups. Ondansetron provided good control of emesis and nausea on day 1 with 71-72% of patients experiencing two or fewer emetic episodes (complete or major responders) and 90-86% of patients reporting nausea as none or mild. There was also no difference in the efficacy of the treatment arms in the control of emesis and nausea on subsequent days of the study period. Both anti-emetic regimens were well-tolerated.", "The purpose of this study was to determine the effectiveness of intravenous ondansetron in preventing vomiting after the administration of intrathecal chemotherapy in children.\n Twenty-six children (ages 18 mo to 15 y) receiving intrathecal chemotherapy with either methotrexate or the combination of methotrexate, hydrocortisone, and Ara-C for the prophylactic treatment of central nervous system leukemia were randomly assigned to receive an infusion of normal saline or ondansetron at one of two doses (0.15 or 0.45 mg/kg) 30 minutes before undergoing the procedure. One hundred forty-six infusions were administered (51 placebo, 47 at the lower ondansetron dose, and 48 at the higher dose). Each patient acted as his or her own control, and each patient was studied at least three times.\n Twenty-three of 26 patients (88.5%) had postprocedural vomiting on at least one occasion. At least one episode of vomiting occurred during the 24 hours after the procedure in fifty-two of the procedures (35.6%). The incidence of vomiting was significantly greater after infusion of placebo than after either low-dose or high-dose ondansetron. The likelihood of severe vomiting was even more significantly reduced by the preadministration of ondansetron. Almost all of the intrathecal treatments associated with severe vomiting occurred after the infusion of placebo.\n Vomiting induced by intrathecal chemotherapy can be greatly reduced by the intravenous administration of ondansetron before the procedure, and severe vomiting can be virtually eliminated.", "The serotonin (5HT3) antagonist ondansetron was compared in a randomised study with metoclopramide and dexamethasone for the prevention of chemotherapy induced emesis. Thirty children aged 1-15 years with acute lymphoblastic leukaemia received 'intensification modules' according to the MRC United Kingdom acute lymphoblastic leukaemia regimen UKALL XI. This contains the moderately emetogenic drugs daunorubicin, etoposide, and cytarabine. Fifteen children received an intravenous loading dose of ondansetron followed by intravenous or oral doses 12 hourly for five days. Fifteen children received intravenous metoclopramide every six hours for three days with a loading dose of dexamethasone, repeated every eight hours for three days intravenously or orally. Efficacy was assessed by a diary card documenting the incidence of nausea, retching, or vomiting. In the 24 hour period after starting chemotherapy, ondansetron was more effective, with a complete or major response rate of 93%, compared with 33% using metoclopramide/dexamethasone.", "Twenty-six children aged 4 to 15 years who were to receive cancer chemotherapy were enrolled in a double-blind, randomized, crossover trial that compared the antiemetic efficacy of a four-drug regimen (the MBDL regimen: metoclopramide, 8 mg/kg; benztropine, 0.04 mg/kg; dexamethasone, 0.7 mg/kg; lorazepam, 0.1 mg/kg), given over 24 hours, with the efficacy of chlorpromazine, 3.3 mg/kg, given in four doses over 24 hours. The MBDL regimen was more effective than chlorpromazine in both objective and subjective measures of antiemetic control. Of 26 children, 23 (89%) had less vomiting on the MBDL regimen, and 20 (77%) of 26 patients or parents preferred this regimen (p less than 0.01). The MBDL regimen reduced the number of vomiting episodes by a mean of 4.0 (p less than 0.01) and reduced the duration of vomiting by a mean of 3.7 hours (p less than 0.01). A moderate level of sedation was documented at some stage in the 24-hour period of observation in 27% on the MBDL regimen and in 35% receiving chlorpromazine. Dystonia was seen in 1 (4%) of 26 children. We conclude that the MBDL regimen is safe in children and more effective than chlorpromazine.", "The antinausea and antivomiting effects of delta-9-tetrahydrocannabinol (THC) in children receiving cancer chemotherapy were compared with those of metoclopramide syrup and prochlorperazine tablets in two double-blind studies. THC was found to be a significantly better antinausea and antivomiting agent, but not all patients obtained relief of nausea and vomiting with THC. In some patients, THC enhanced appetite during a course of chemotherapy. In two patients, a \"high\" associated with THC administrationwas reported. Drowsiness was reported significantly more frequently with THC.", "To perform a cost-effectiveness analysis (CEA) between a standard antiemetic regimen-chlorpromazine + dexamethasone (CPM-DEX)- and a 5-HT3 receptor antagonist-tropisetron (TROP)--in the control of acute emesis induced by highly emetogenic chemotherapy in children, considering two analytic perspectives: hospital and patients.\n The CEA was performed by constructing a decision tree, for both analytic perspectives, of the possible outcomes of treatment with TROP (single 0.2 mg/kg i.v.) or CPM (5-15 mg i.v. infusion for 3 doses) plus DEX (2 mg/m2 i.v. bolus i.v. x2). The patients were stratified by age in two groups (2-12 and 13-17). To estimate the probability of each endpoint at the decision tree we have taken as a base a trial developed in the Department of Pediatrics. Direct medical cost of primary therapy, failure, complications and side effects were included in the cost calculations.\n From patients' analytic perspective, TROP was more cost-effective than CPM-DEX for both groups of patients. Discrepancy between both analytic perspectives in 13-17 year-old patient's group was resolved in favour of the option chosen from the patients' analytic perspective (TROP). Sensitivity analysis showed the reliability of the results.\n 1. TROP was more cost-effective than CPM-DEX. 2. Taking into account the patients' analytic perspective is essential when we compare antiemetics pharmacoeconomically. 3. It seems necessary to increase the effectiveness of TROP in pediatric patients receiving highly emetogenic chemotherapy with strategies such as the addition of a steroid.", "Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin.\n In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 microg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1-23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 microg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls.\n Patients in the granisetron 10 and 40 microg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated.\n We conclude that granisetron 10 and 40 microg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.", "This randomised study was performed to assess the anti-emetic efficacy and tolerability of two-dose regimens of granisetron in children with leukaemia. 49 children with leukaemia were treated with three consecutive courses of high-dose methotrexate or cytarabine regimen. During the first course, patients were evaluated regarding the emetogenicity of each regimen. They were randomised in a crossover manner to receive 20 or 40 micrograms/kg of granisetron before the second and third course of chemotherapy. Neither emesis nor severe appetite loss were observed in over 80% of patients within the first 24 h in all treatment groups. There was no significant difference in the anti-emetic efficacy between the two-dose regimens of granisetron. However, complete protection was achieved less frequently on days 2 and 3. Older children and girls appeared to be less well protected. No adverse events attributable to granisetron were observed. Granisetron dose regimens of 20 and 40 micrograms/kg are, comparably, well tolerated and effective in controlling chemotherapy-induced emesis in the first 24 h, though this protection fails thereafter, particularly in older patients and girls.", "nan", "nan", "A prospective randomised double blind crossover trial was conducted comparing the new synthetic cannabinoid nabilone with oral domperidone in a group of children receiving repeated identical courses of emetogenic chemotherapy for a variety of malignant diseases. Eighteen of 23 consecutive eligible children, aged 10 months to 17 years, completed the trial. When taking nabilone they experienced significantly fewer vomiting episodes and less nausea, and two thirds expressed a preference for the drug. The most common side effects of treatment with nabilone were somnolence and dizziness, with one patient being disturbed by hallucinations. The results indicate that nabilone is an effective antiemetic for children having chemotherapy, even for young children. It seems to be superior in this respect to domperidone, and although it has a higher incidence of side effects, these are mostly acceptable to patients. It can be recommended as an alternative to conventional antiemetic treatment throughout childhood.", "This prospective study was designed to compare the efficacy of ondansetron with granisetron in terms of complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia (ALL) undergoing moderately emetogenic cyclophosphamide-based chemotherapy. The costs for both treatments are also examined. A total of 33 children (mean age: 7.8 +/- 4.9 year) were studied during 66 chemotherapy cycles. Analysis was based on 33 courses of a single oral dose of granisetron and 33 courses of ondansetron incorporating 2 intravenous doses of ondansetron 0.15 mg/kg followed by 1 dose of the same dosage orally. There was no significant difference between the 2 treatments in terms of overall efficacy (McNemar's chi-square test). Twenty of 33 patients (60.6%) receiving granisetron and 15 of 33 patients (45.5%) receiving ondansetron experienced no emesis 24 h after chemotherapy (p = .227). Boys experienced greater rates of vomiting than did girls despite antiemetic treatment; however, no apparent reason for the gender discrepancy was noted. Both antiemetic regimens have similar antiemetic efficacy for treating the moderately emetogenic effects associated with cyclophosphamide-based chemotherapy. It is possible that the granisetron regimen may be preferable because it is simpler to administer and more cost-effective.", "A double-blind randomized comparison (protocol S3AB4003, Glaxo Wellcome, Great Britain) carried out in a group of 52 children showed that the 5-HT3-receptor antagonist ondansetron (in syrup) effectively prevented vomiting, nausea and loss of appetite caused in combination chemotherapy with highly- or moderately emetogenic cytostatic drugs in 92.3; 69.3 and 81.0%, respectively. Treatment was given to patients who were on dexamethasone. With intravenous injection of ondansetron plus dexamethasone, per os, said indices were 88.5; 73.2%; 73.2%, respectively, thus showing no significant differences. No side-effects were observed with either regimen.", "In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.", "This is the first prospective randomized study comparing commonly used antiemetics in children receiving cancer chemotherapy. We compared metoclopramide (MCP) with chlorpromazine (CLP), both administered in conventional doses, in 50 cancer patients aged 6 to 18 years who were receiving emetic chemotherapy. CLP proved significantly better than MCP in reducing both the frequency of vomiting (P less than .05) and the duration of nausea and vomiting (P less than .025). Extrapyramidal reactions (EPRs) were more common in MCP-treated patients. We conclude that, in the standard doses used, CLP is a better overall antiemetic than MCP for children receiving intensive chemotherapy. However, further prospective pediatric studies of antiemetic combinations are needed.", "This prospective, double-blind, randomized study compares the antiemetic efficacy of an equivalent dose of ondansetron administered as a single high dose or as multiple standard doses in pediatric oncology patients. Thirty-one chemotherapy-naive patients were randomized at diagnosis to receive either single high-dose ondansetron (0.6 mg/kg, maximum dose 32 mg) or multiple standard-dose ondansetron (0.15 mg/kg, maximum dose 8 mg, every 4 hr for four doses). Antiemetic efficacy was assessed by an emesis scale described as follows: 1, no nausea or emesis; 2, nauseous but able to eat; 3, nauseous and unable to eat; and 4, emesis. Sixteen patients received high-dose and 15 received standard-dose ondansetron. Patients receiving moderately or severely emetogenic chemotherapy were evenly distributed between the two treatment groups. Eighty-one percent of patients receiving high-dose and 80% receiving standard-dose ondansetron rated 1 or 2 on the emesis scale (p = 0.93). No patient experienced any clinical or laboratory toxicity. Our study suggests that single high-dose ondansetron is as efficacious as the multiple standard-dose regimen and is well tolerated. Its use will facilitate the administration of ondansetron in pediatric patients receiving chemotherapy.", "To compare the efficacy and safety of intravenously administered granisetron with those of chlorpromazine plus dexamethosone in the prevention of ifosmamide-induced emesis in children with malignant disease.\n Eighty-eight children, aged 2 to 17 years, were scheduled for ifosfamide therapy (> or = 3 gm/m2) for 2 or 3 consecutive days. On each day, children received granisetron, 20 microgram/kg intravenously, before ifosfamide therapy, plus up to two more doses within 24 hours if required, or chlorpromazine, 0.3 to 0.5 mg/kg intravenously, every 4 to 6 hours, plus dexamethasone, 2 mg/m2 intravenously every 8 hours.\n During the initial 24 hours, significantly fewer episodes of vomiting were recorded after granisetron administration (median number, 1.5 vs 7.0; p = 0.001), and the percentages of children having no more than one vomiting episode (51% granisetron vs 21% chlorpromazine-dexamethasone) and no worse than mild nausea (67% granisetron vs 38% chlorpromazine-dexamethasone) were lower after granisetron therapy (p < 0.01). Fewer children had sedation with granisetron (2 vs 19; p < 0.001); there were no extrapyramidal reactions during granisetron therapy compared with two during control therapy.\n Granisetron was superior to chlorpromazine-dexamethasone antiemetic therapy for children receiving ifosfamide therapy and deserves further study during other chemotherapy regimens.", "nan" ]

[ "9442174", "3620398", "7211972", "18715415", "19250364" ]

[ "Dysfunctional labour: a randomised trial.", "A randomized control study of oxytocin augmentation of labour. 1. Obstetric outcome.", "Randomized trial of ambulation versus oxytocin for labor enhancement: a preliminary report.", "A randomised controlled trial of early versus delayed oxytocin augmentation to treat primary dysfunctional labour in nulliparous women.", "Early versus delayed oxytocin augmentation in nulliparous women with prolonged labour--a randomised controlled trial." ]

[ "Sixty-one women making slow progress in the active phase of spontaneous labour with intact membranes were randomised to oxytocin and amniotomy, amniotomy only or expectant management. The data show that oxytocin significantly increases the rate of cervical dilatation and shortens prolonged labour, when compared with amniotomy alone and expectant management (P = 0.0144 and 0.0006, respectively). The impact on the operative delivery rate and neonatal outcome is difficult to assess due to the small number of relevant adverse outcomes. Women reported higher satisfaction score in the two groups where intervention followed the diagnosis of dysfunctional labour.", "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.", "Published reports imply that intrapartum ambulation may improve labor. This suggests the possible efficacy of ambulation in labors requiring augmentation, provided that adequate monitoring surveillance is maintained. Fourteen patients who failed to progress in active-phase labor, and who required augmentation for \"inadequate\" contractions were randomized into ambulation (eight) and oxytocin (six) groups. Internal fetal monitoring was used in all patients for 30 minute baseline and 2 hour study periods, with two-channel telemetry used in ambulating patients. Oxytocin was administered by infusion pump. Study parameters included changes in cervical dilation and station, contraction frequency, intensity and baseline tonus, and uterine activity. Labor progress was slightly but not significantly better in the ambulatory group. A mean increase in uterine activity units (UAU) in the ambulatory group was immediate to ranges not reached in the oxytocin group for 2 hours. Increase in Montevideo units was slightly greater in the ambulatory group during the first hour, but was exceeded by the oxytocin group during the second hour. These initial observations seem to indicate that, in terms of labor progress and initial effects on uterine activity, ambulation is as effective as oxytocin for the enhancement of labor and warrants further investigation.", "Oxytocin is widely used to speed up slow labour, especially in nulliparous women, but randomised trials, apart from one reported only in abstract, have been too small to exclude important effects.\n To test the hypothesis that early use of oxytocin reduces the need for caesarean delivery.\n A randomised controlled trial.\n Twelve obstetric units within the Northern and Yorkshire regions in the North East of England.\n A total of 412 low-risk nulliparous women in spontaneous labour at term, who had been diagnosed with primary dysfunctional labour were recruited from January 1999 to December 2001.\n Immediate oxytocin administration (active group) or oxytocin withheld for up to 8 hours (conservative group).\n Caesarean section and operative vaginal delivery rates. The length of labour measured from the time of randomisation to delivery. The rate of maternal Edinburgh Postnatal Depression Scale (EPDS) greater than 12 (major depression) within 48 hours of delivery.\n The caesarean section rates were 13.5% active versus 13.7% controls (OR 0.98, 95% CI 0.6-1.7). Operative delivery, 24.5% versus 30.9% (OR 0.73, 95% CI 0.5-1.1). The median (interquartile range) randomisation to delivery interval in the active group was 5 hours 52 minutes (3:57-8:28) and in the conservative group 9 hours 8 minutes (5:06-13:16) (P < 0.001). The rate of EPDS >12 was 20% in the active arm versus 15% among controls (OR 1.26, 95% CI 0.7-2.2). There was one perinatal death in each group and no major differences in perinatal outcomes.\n Among nulliparous women with primary dysfunctional labour, early use of oxytocin does not reduce caesarean section or short-term postnatal depression. However, it shortens labour considerably and may reduce operative vaginal deliveries.", "To study the effects of early versus delayed oxytocin augmentation on the obstetrical and neonatal outcome in nulliparous women with spontaneous but prolonged labour.\n Randomised controlled study.\n Two delivery units in Sweden.\n Healthy nulliparous women with normal pregnancies, spontaneous onset of active labour, a cervical dilatation of 4-9 cm and no progress in cervical dilatation for 2 hours and for an additional hour if amniotomy was performed due to slow progress.\n Women (n = 630) were randomly allocated either to labour augmentation by oxytocin infusion (early oxytocin group) or to postponement of oxytocin augmentation for another 3 hours (expectant group).\n Mode of delivery (spontaneous vaginal or instrumental vaginal delivery or caesarean section) and time from randomisation to delivery.\n The caesarean section rate was 29 of 314 (9%) in the early oxytocin group and 34 of 316 (11%) in the expectant group (OR 0.8, 95% CI 0.5-1.4), and instrumental vaginal delivery 54 of 314 (17%) in the early oxytocin versus 38 of 316 (12%) in the expectant group (OR 1.5, 95% CI 0.97-2.4). Early initiation of oxytocin resulted in a mean decrease of 85 minutes in the randomisation to delivery interval.\n Early administration of oxytocin did not change the rate of caesarean section or instrumental vaginal delivery but shortened labour duration significantly in women with a 2-hour arrest in cervical dilatation. No other clear benefits or harms were seen between early and delayed administration of oxytocin." ]

[ "16817011", "11386930", "17483124", "11439963", "17622343", "17179052" ]

[ "Improvement in serial cardiopulmonary exercise testing following enzyme replacement therapy in Fabry disease.", "Enzyme replacement therapy in Fabry disease: a randomized controlled trial.", "Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa.", "Safety and efficacy of recombinant human alpha-galactosidase A--replacement therapy in Fabry's disease.", "Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg.", "Agalsidase-beta therapy for advanced Fabry disease: a randomized trial." ]

[ "Fabry disease is an X-linked genetic disorder resulting in the accumulation of glycosphingolipids in various organs, leading to exercise intolerance and early mortality. Enzyme replacement therapy (ERT) has recently been approved for use in Fabry patients. GOALS OF STUDY: To assess baseline cardiopulmonary exercise characteristics in both invasive and noninvasive tests and to study the impact of ERT on exercise.\n A total of 15 patients with Fabry disease underwent baseline cardiopulmonary exercise tests. Six patients were randomized 2:1 to receive either ERT or placebo. We performed serial cardiopulmonary exercise tests at baseline and every 3 months over a period of at least 18 months. The baseline test was compared to the last two exercise tests for each patient.\n Mean age was 32 years. Mean VO2max was 1.680 +/- 0.67 L/min and increased by 0.459 +/- 0.64 L/min in the patients receiving ERT. Mean VO2max was 1.462 +/- 0.25 L/min and decreased by 0.116 +/- 0.44 L/min in patients on placebo. Mean oxygen pulse (VO2/HR) increased by 1.71 with enzyme, but increased only 0.025 in patients taking placebo. Estimated stroke volume (SV) increased by 10 ml in patients on ERT.\n In this small cohort, exercise tolerance increased in patients receiving enzyme replacement therapy. Cardiopulmonary exercise testing is a useful test in measuring the response to therapy in Fabry disease patients.", "Fabry disease is a metabolic disorder without a specific treatment, caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). Most patients experience debilitating neuropathic pain and premature mortality because of renal failure, cardiovascular disease, or cerebrovascular disease.\n To evaluate the safety and efficacy of intravenous alpha-gal A for Fabry disease.\n Double-blind placebo-controlled trial conducted from December 1998 to August 1999 at the Clinical Research Center of the National Institutes of Health.\n Twenty-six hemizygous male patients, aged 18 years or older, with Fabry disease that was confirmed by alpha-gal A assay.\n A dosage of 0.2 mg/kg of alpha-gal A, administered intravenously every other week (12 doses total).\n Effect of therapy on neuropathic pain while without neuropathic pain medications measured by question 3 of the Brief Pain Inventory (BPI).\n Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46) to 4.3 (0.73) in patients treated with alpha-gal A vs no significant change in the placebo group (P =.02). Pain-related quality of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving alpha-gal A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P =.05). In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving alpha-gal vs a 16.5% increase for placebo (P =.01). Mean inulin clearance decreased by 6.2 mL/min for patients receiving alpha-gal A vs 19.5 mL/min for placebo (P =.19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s) for patients receiving alpha-gal A vs a decrease of 16.1 mL/min (0.3 mL/s) for placebo (P =.02). In patients treated with alpha-gal A, there was an approximately 50% reduction in plasma glycosphingolipid levels, a significant improvement in cardiac conduction, and a significant increase in body weight.\n Intravenous infusions of alpha-gal A are safe and have widespread therapeutic efficacy in Fabry disease.", "Anderson-Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb(3)) in the lysosomes of cells throughout the body that ultimately results in premature death from renal, cardiac or cerebrovascular complications. Until recently, there was no effective therapy available for this disease. The present study was designed to assess the safety and efficacy of enzyme replacement therapy with agalsidase alfa on the cardiac manifestations of Anderson-Fabry disease.\n The effects of therapy with agalsidase alfa on cardiac structure and function were assessed in a randomised, double-blind, placebo-controlled study of 15 adult male patients with Anderson-Fabry disease. The following parameters were measured at baseline and 6 months: left ventricular mass, QRS duration and levels of Gb(3) in cardiac tissue, urine sediment and plasma. After 6 months of the randomised trial patients were enrolled in a 2-year open-label extension study.\n Left ventricular mass, as measured by MRI, was significantly reduced following 6 months of treatment with agalsidase alfa compared with placebo (p = 0.041). A mean 20% reduction in myocardial Gb(3) content as assessed by serial transvenous endomyocardial biopsies was demonstrated over the 6 months of enzyme replacement compared to a mean 10% increase in patients receiving placebo (p = 0.42)\n Enzyme replacement therapy with agalsidase alfa resulted in regression of the hypertrophic cardiomyopathy associated with Anderson-Fabry disease.", "Fabry's disease, lysosomal alpha-galactosidase A deficiency, results from the progressive accumulation of globotriaosylceramide and related glycosphingolipids. Affected patients have microvascular disease of the kidneys, heart, and brain.\n We evaluated the safety and effectiveness of recombinant alpha-galactosidase A in a multicenter, randomized, placebo-controlled, double-blind study of 58 patients who were treated every 2 weeks for 20 weeks. Thereafter, all patients received recombinant alpha-galactosidase A in an open-label extension study. The primary efficacy end point was the percentage of patients in whom renal microvascular endothelial deposits of globotriaosylceramide were cleared (reduced to normal or near-normal levels). We also evaluated the histologic clearance of microvascular endothelial deposits of globotriaosylceramide in the endomyocardium and skin, as well as changes in the level of pain and the quality of life.\n In the double-blind study, 20 of the 29 patients in the recombinant alpha-galactosidase A group (69 percent) had no microvascular endothelial deposits of globotriaosylceramide after 20 weeks, as compared with none of the 29 patients in the placebo group (P<0.001). Patients in the recombinant alpha-galactosidase A group also had decreased microvascular endothelial deposits of globotriaosylceramide in the skin (P<0.001) and heart (P<0.001). Plasma levels of globotriaosylceramide were directly correlated with clearance of the microvascular deposits. After six months of open-label therapy, all patients in the former placebo group and 98 percent of patients in the former recombinant alpha-galactosidase A group who had biopsies had clearance of microvascular endothelial deposits of globotriaosylceramide. The incidence of most treatment-related adverse events was similar in the two groups, with the exception of mild-to-moderate infusion reactions (i.e., rigors and fever), which were more common in the recombinant alpha-galactosidase A group. IgG seroconversion occurred in 88 percent of patients who received recombinant alpha-galactosidase A.\n Recombinant alpha-galactosidase A replacement therapy cleared microvascular endothelial deposits of globotriaosylceramide from the kidneys, heart, and skin in patients with Fabry's disease, reversing the pathogenesis of the chief clinical manifestations of this disease.", "Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial.\n Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54.\n Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease.\n International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534].", "Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement.\n To see whether agalsidase beta delays the onset of a composite clinical outcome of renal, cardiovascular, and cerebrovascular events and death in patients with advanced Fabry disease.\n Randomized (2:1 treatment-to-placebo randomization), double-blind, placebo-controlled trial.\n 41 referral centers in 9 countries.\n 82 adults with mild to moderate kidney disease; 74 of whom were protocol-adherent.\n Intravenous infusion of agalsidase beta (1 mg per kg of body weight) or placebo every 2 weeks for up to 35 months (median, 18.5 months).\n The primary end point was the time to first clinical event (renal, cardiac, or cerebrovascular event or death). Six patients withdrew before reaching an end point: 3 to receive commercial therapy and 3 due to positive or inconclusive serum IgE or skin test results. Three patients assigned to agalsidase beta elected to transition to open-label treatment before reaching an end point.\n Thirteen (42%) of the 31 patients in the placebo group and 14 (27%) of the 51 patients in the agalsidase-beta group experienced clinical events. Primary intention-to-treat analysis that adjusted for an imbalance in baseline proteinuria showed that, compared with placebo, agalsidase beta delayed the time to first clinical event (hazard ratio, 0.47 [95% CI, 0.21 to 1.03]; P = 0.06). Secondary analyses of protocol-adherent patients showed similar results (hazard ratio, 0.39 [CI, 0.16 to 0.93]; P = 0.034). Ancillary subgroup analyses found larger treatment effects in patients with baseline estimated glomerular filtration rates greater than 55 mL/min per 1.73 m2 (hazard ratio, 0.19 [CI, 0.05 to 0.82]; P = 0.025) compared with 55 mL/min per 1.73 m2 or less (hazard ratio, 0.85 [CI, 0.32 to 2.3]; P = 0.75) (formal test for interaction, P = 0.09). Most treatment-related adverse events were mild or moderate infusion-associated reactions, reported by 55% of patients in the agalsidase-beta group and 23% of patients in the placebo group.\n The study sample was small. Only one third of the patients experienced clinical events, and some patients withdrew before experiencing any event.\n Agalsidase-beta therapy slowed progression to the composite clinical outcome of renal, cardiac, and cerebrovascular complications and death compared with placebo in patients with advanced Fabry disease. Therapeutic intervention before irreversible organ damage may provide greater clinical benefit." ]

[ "16571204" ]

[ "Author contacts for retrieval of data for a meta-analysis on exercise and diet restriction." ]

[ "The mode of contact and response levels of authors who had been asked to provide missing or incomplete data for a systematic review on diet and exercise interventions for weight loss was examined.\n We contacted authors by electronic mail, letter, or both. Survival analyses were performed with the Kaplan-Meier method to determine differences in the proportion of responders over time among the different modes of contact and to determine whether response rates differed between authors from the United States and those from other countries. Logistic regression was used to determine whether the number of items requested and publication date influenced the likelihood of response.\n Two hundred forty-one (39.9 percent) studies had missing or incomplete data (e.g., sample size, age, caloric restriction, exercise amount, and so on). We were unable to locate ninety-five authors (39.4 percent). Of the remaining authors, forty-six authors (31.5 percent) responded to information requests. Time to respond differed by contact method (p < .05): e-mail (3 +/- 3 days), letter (27 +/- 30 days), and both (13 +/-12 days). Response rates from U.S. authors did not differ from those of other countries.\n Our study suggests poor success in the acquisition of essential information. Given considerable time and resources, weight loss studies require improved reporting standards to minimize the relatively unsuccessful attempt to contact authors for important and necessary information." ]

[ "21615866", "17825472", "20417924", "9350017", "18639876", "19254586", "20816153", "16651950" ]

[ "A randomized, controlled study comparing the cosmetic outcome of a new wound closure device with Prolene suture closing caesarean wounds.", "Scar appearance of different skin and subcutaneous tissue closure techniques in caesarean section: a randomized study.", "Cosmetic outcomes of various skin closure methods following cesarean delivery: a randomized trial.", "Closure of Pfannenstiel skin incisions. Staples vs. subcuticular suture.", "Absorbable versus nonabsorbable sutures for subcuticular skin closure of a transverse suprapubic incision.", "A randomized study comparing skin closure in cesarean sections: staples vs subcuticular sutures.", "Randomized controlled trial of wound complication rates of subcuticular suture vs staples for skin closure at cesarean delivery.", "Evaluation of a novel technique for wound closure using a barbed suture." ]

[ "A prospective, randomised study was conducted to compare the wound closure performance and cosmetic outcome of caesarean section wounds closed with traditional Prolene suture or a new wound closure device (Leukosan(®) SkinLink). Sixty-one patients referred to primary section were allocated to wound closure with either Leukosan(®) SkinLink or Prolene suture. Cosmetic outcome as the primary measure was evaluated by the patient, the surgeon as well as by independent examiners blinded to the method of wound closure. Evaluations were recorded at 3, 6 and 12 months following wound closure. Both methods of wound closure scored equally high on the visual analogue scale for cosmetic evaluation at the 3-, 6- and 12-month follow-ups as assessed by the patient, surgeon and the blinded observers. The study has shown that innovative methods for wound closure compared with traditional methods such as suture providing excellent cosmetic results represent a valid alternative to physician and patient for surgical incisions.\n © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.", "To determine the role of skin and subcutaneous space closure in caesarean section on the cosmetic appearance of the scar and the patients' satisfaction.\n 153 patients undergoing caesarean section without prior abdominal delivery were included and randomly assigned in a non-blinded study to four different combinations of skin and subcutaneous tissue closure. The scar was assessed after a period of at least 4 months by a self-developed protocol and the patient was asked to complete a survey regarding her satisfaction with the scar.\n One hundred patients were eligible for long-term evaluation of the scar. Skin closure by either staples or intracutaneous suture in combination with closure or non-closure of the subcutaneous space has a comparable outcome in view of cosmetic outcome and patient satisfaction.\n All four methods of skin closure seem to be a reasonable choice in caesarean section because they have comparable cosmetic outcome, do not differ with respect to the patients' satisfaction and bear comparable costs.", "The objective of the study was to compare scar quality associated with different types of wound closure methods after cesarean section (CS).\n Patients were randomized to have skin closure following CS with either staples or 3 different types of subcuticular sutures. Scar quality was evaluated 2 and 6 months postoperatively. The Vancouver Scar Scale, the Patient and Observer Scar Assessment Scale (POSAS), and a visual analog scale were used as scar assessment tools.\n Of the 180 patients who were recruited, 123 successfully completed the study. No difference in both subjective and objective scar rating was detected across groups at either 2 months or 6 months. In the overall study population, objective scores correlated with patient rating, and correlation was strongest between the observer and patient components of the POSAS (r = 0.48).\n In women undergoing CS, stapled wounds and those closed with subcuticular sutures result in equivalent cosmetic appearance of the scar.\n Copyright (c) 2010 Mosby, Inc. All rights reserved.", "To compare skin closure with staples and subcuticular suture.\n Obstetric patients undergoing cesarean section with a Pfannenstiel incision were prospectively randomized to skin closure with staples or subcuticular suture. Pain and cosmesis were assessed postoperatively.\n Patients reported significantly less pain following subcuticular closure at both the time of discharge (P < or = .01) and the postoperative visit (P < or = .002). Incisions closed with subcuticular suture were found to be more cosmetically attractive by both patients (P = .04) and physicians (P = .01) at the postoperative visit.\n Pfannenstiel skin incisions closed with subcuticular closure following cesarean section result in less postoperative discomfort and are more cosmetically appealing at the six-week postoperative visit as compared to incisions closed with staples.", "nan", "We sought to compare postoperative pain according to the skin closure method (subcuticular sutures vs staples) after an elective term cesarean section.\n A randomized controlled trial of 101 women was performed. Women were randomly assigned to subcuticular sutures or staples. Operative technique and postoperative analgesia were standardized. Stratification was used for primary vs repeat cesareans. Analog pain and satisfaction scales ranging from 0-10 were completed at postoperative days 1 and 3, and at 6 weeks postoperatively. A digital photograph of the incision was taken at 6 weeks postoperatively and evaluated by 3 independent blinded observers.\n Pain at 6 weeks postoperatively was significantly less in the staple group (0.17 vs 0.51; P = .04). Operative time was shorter in that group (24.6 vs 32.9 minutes; P < .0001). No difference was noted for incision appearance and women's satisfaction.\n Staples are the method of choice for skin closure for elective term cesareans in our population.", "The purpose of this study was to determine the wound complication rates and patient satisfaction for subcuticular suture vs staples for skin closure at cesarean delivery.\n This was a randomized prospective trial. Subjects who underwent cesarean delivery were assigned randomly to stainless steel staples or subcuticular 4.0 Monocryl sutures. The primary outcomes were composite wound complication rate and patient satisfaction.\n A total of 435 patients were assigned randomly. Staple closure was associated with a 4-fold increased risk of wound separation (adjusted odds ratio [aOR], 4.66; 95% confidence interval [CI], 2.07-10.52; P < .001). Having a wound complication was associated with a 5-fold decrease in patient satisfaction (aOR, 0.18; 95% CI, 0.09-0.37; P < .001). After confounders were controlled for, there was no difference in satisfaction between the treatment groups (aOR, 0.71; 95% CI, 0.34-1.50; P = .63).\n Use of staples for cesarean delivery closure is associated with an increased risk of wound complications. Occurrence of a wound complication is the most important factor that influenced patient satisfaction.\n Published by Mosby, Inc.", "Suture knots present several disadvantages in wound closure, because they are tedious to tie and place ischemic demands on tissue. Bulky knots may be a nidus for infection, and they may extrude through skin weeks after surgery. Needle manipulations during knot-tying predispose the surgeon to glove perforation. A barbed suture was developed that is self-anchoring, requiring no knots or slack management for wound closure. The elimination of knot tying may have advantages over conventional wound closure methods.\n This prospective, randomized, controlled trial was designed to show that the use of barbed suture in dermal closure of the Pfannenstiel incision during nonemergent cesarean delivery surgery produces scar cosmesis at 5 weeks that is no worse than that observed with conventional closure using 3-0 polydioxanone suture. Cosmesis was assessed by review of postoperative photographs by a blinded, independent plastic surgeon using the modified Hollander cosmesis score. Secondary endpoints included infection, dehiscence, pain, closure time, and other adverse events.\n The study enrolled 195 patients, of whom 188 were eligible for analysis. Cosmesis scores did not significantly differ between the barbed suture group and the control group. Rates of infection, dehiscence, and other adverse events did not significantly differ between the two groups. Closure time and pain scores were comparable between the groups.\n The barbed suture represents an innovative option for wound closure. With a cosmesis and safety profile that is similar to that of conventional suture technique, it avoids the drawbacks inherent to suture knots." ]

[ "17139218" ]

[ "Treatment of traumatic thoracolumbar spine fractures: a multicenter prospective randomized study of operative versus nonsurgical treatment." ]

[ "Multicenter prospective randomized trial.\n To test the hypotheses that thoracolumbar AO Type A spine fractures without neurologic deficit, managed with short-segment posterior stabilization will show an improved radiographic outcome and at least the same functional outcome as compared with nonsurgically treated thoracolumbar fractures.\n There are various opinions regarding the ideal management of thoracolumbar Type A spine fractures without neurologic deficit. Both operative and nonsurgical approaches are advocated.\n Patients were randomized for operative or nonsurgical treatment. Data sampling involved demographics, fracture classifications, radiographic evaluation, and functional outcome.\n Sixteen patients received nonsurgical therapy, and 18 received surgical treatment. Follow-up was completed for 32 (94%) of the patients after a mean of 4.3 years. At the end of follow-up, both local and regional kyphotic deformity was significantly less in the operatively treated group. All functional outcome scores (VAS Pain, VAS Spine Score, and RMDQ-24) showed significantly better results in the operative group. The percentage of patients returning to their original jobs was found to be significantly higher in the operative treated group.\n Patients with a Type A3 thoracolumbar spine fracture without neurologic deficit should be treated by short-segment posterior stabilization." ]

[ "8860884", "8554838" ]

[ "Effect of progesterone and its 5 alpha and 5 beta metabolites on symptoms of premenstrual syndrome according to route of administration.", "Investigation of the efficacy of progesterone pessaries in the relief of symptoms of premenstrual syndrome. progesterone Study Group." ]

[ "Orally administered progesterone may have advantages over other routes of administration in the treatment of premenstrual syndrome (PMS) because of substantially higher levels of the anxiolytic metabolites 5 alpha and 5 beta pregnanolone. The only previous placebo-controlled trial which used oral progesterone reported beneficial effects in the treatment of PMS. The present study, a double-blind crossover trial, compared the administration of 300 mg daily oral progesterone with 200 mg daily vaginal progesterone and matched placebos for 10 days premenstrually. Although there was a significant treatment effect on symptoms, no difference between active treatments and placebo was found. The trial was terminated with 25 women completing treatment as it was evident that no clinically significant effect of either form of progesterone was likely to be detected even with twice the sample size. Serum levels of progesterone and metabolites showed that oral administration resulted in supraphysiological levels of 5 alpha and 5 beta metabolites and there was a negative correlation between 5 alpha pregnanolone levels and anxiety. However, this did not translate to overall reduction in premenstrual distress or anxiety beyond that achieved by placebo, as measured by validated questionnaires.", "A variety of definitions have been applied to premenstrual syndrome. The severity of the syndrome is also variable.\n A study was undertaken to compare progesterone pessaries with placebo in the relief of symptoms of premenstrual syndrome. In this study the condition was characterized by a wide range of symptoms recurring in the late luteal phase but absent in the follicular phase (that is, the specific definition published by Dalton in 1953).\n A multicentre, prospective, double-blind, randomized, parallel group study was undertaken by 45 general practitioners. Patients were deemed eligible after two prospective menstrual cycles of observation (selection phase) in which a precise definition of symptoms was applied. Patients were randomized to use either progesterone pessaries (400 mg twice a day) or matching placebo, by vaginal or rectal administration, from 14 days before the expected onset of menstruation until the onset of vaginal bleeding, for four consecutive cycles. Baseline data for the outcome variables were determined in the selection phase. The main outcome variables were changes in the severity (categorized as none, mild, moderate or severe) of each patient's most severe symptom, and in the average score of all the patient's symptoms characteristic of premenstrual syndrome. Spontaneous reports of adverse events were recorded.\n A total of 281 patients were screened for premenstrual syndrome; of these, 141 patients were randomized to treatment or placebo groups. Efficacy was evaluated in 93 patients. Reductions in the scores of the highest scoring, most severe, symptoms and in the average symptom score, were consistently observed in patients receiving progesterone pessaries and in those receiving placebo. The response to progesterone was greater than to placebo during each cycle; the differences were clinically and statistically significant. Adverse events were reported by 51% of patients in the progesterone treatment group and by 43% in the placebo group. Irregularity of menstruation, vaginal pruritus and headache were reported more frequently by patients taking active therapy.\n In this study, progesterone, given as pessaries by vaginal or rectal administration, was more effective than placebo in the relief of symptoms of premenstrual syndrome in a population of patients selected by strict entry criteria." ]

[ "22832887", "21478660", "19169102", "22118480", "19714275" ]

[ "Sling compared with plate osteosynthesis for treatment of displaced midshaft clavicular fractures: a randomized clinical trial.", "Comparison between operative and nonoperative treatment methods in the management of comminuted fractures of the clavicle.", "Elastic stable intramedullary nailing versus nonoperative treatment of displaced midshaft clavicular fractures-a randomized, controlled, clinical trial.", "Intramedullary nailing of clavicular midshaft fractures in adults using titanium elastic nail.", "Acute operative stabilization versus nonoperative management of clavicle fractures." ]

[ "Few randomized controlled trials have compared operative with nonoperative treatment of clavicular fractures.\n Patients with displaced midshaft clavicular fractures were randomized either to nonoperative treatment with a sling or to operative treatment with a stainless steel 3.5-mm reconstruction plate. Outcome measures were the Constant shoulder score, DASH (Disabilities of the Arm, Shoulder and Hand) score, pain, fracture-healing, and complications. The null hypothesis was that the Constant and DASH scores would not differ between the groups at the one-year follow-up evaluation.\n In accordance with the power analysis, we included sixty patients in the study; thirty-two were randomized to the nonoperative group and twenty-eight to the operative group. We found no difference in the Constant score (p = 0.75), the DASH score (p = 0.89), or pain (p = 0.98) between the groups at the one-year follow-up evaluation. All fractures in the operative group healed, but six nonunions (24%) occurred in the nonoperative group.\n One year after a displaced midshaft clavicular fracture, nonoperative treatment resulted in a higher nonunion rate but similar function and disability compared with operative treatment.", "To evaluate the outcome and satisfaction of closed treatment versus open reduction and internal fixation in comminuted clavicular fractures.\n Sixty patients with displaced clavicular fractures were randomized into operative (29 patients) and nonoperative (31 patients) groups. Three patients in the operative group did not accept the surgery, and seven patients in the nonoperative group did not complete the one-year follow-up. Outcomes were assessed using the Disability of the Arm, Shoulder and Hand (DASH) score, Constant shoulder score, specific questions regarding patients' final satisfaction, physical examination, measurement of the shortening of the clavicular length, and plain radiographs.\n There was one nonunion in the operative group and one in the nonoperative group. The nonunion in operative group was the result of the only infection in this group. Four malunions were developed in the operative group and nineteen malunions in the nonoperative treatment, (p<0.001). Three patients in the operative group were completely dissatisfied with their treatment. Eighteen patients in the nonoperative group were partially satisfied. Pain was the main reason for dissatisfaction in this group. The mean shortening of the clavicle was 26.5 mm in the nonoperative group and 4.0 mm in the operative group. The mean DASH score for the operative and nonoperative groups were 8.6 and 21.3, respectively (p<0.001); and the Constant shoulder scores were 89.8 and 78.8 (p<0.001).\n Open reduction and internal fixation of comminuted fractures of the clavicle using a reconstruction plate is an effective treatment modality. Despite the variety of complications, this method has a higher satisfaction rate than conservative treatment.", "To compare elastic stable intramedullary nailing (ESIN) with nonoperative treatment of fully displaced midshaft clavicular fractures in adults.\n The study was a randomized, controlled, clinical trial.\n Level 1 trauma center.\n Sixty patients between 18 and 65 years of age participated and completed the study. They were randomized to either operative or nonoperative treatment with a 2-year follow-up.\n Thirty patients were treated with a simple shoulder sling and 30 patients with ESIN within 3 days after trauma.\n Complications after operative and nonoperative treatments, Disabilities of the Arm, Shoulder and Hand (DASH) score and Constant Shoulder Score for outcome measurement, and clavicular shortening.\n Fracture union was achieved in all patients in the operative group, whereas nonunion was observed in 3 of 30 patients of the nonoperative group. Two symptomatic malunions required corrective osteotomy in the nonoperative group. Medial nail protrusion occurred in 7 cases in the operative group. Implant failure with revision surgery was necessary in 2 patients after an additional adequate trauma. DASH scores were lower in the operative group throughout the first 6 months and 2 years after trauma, with a significant difference during the first 18 weeks. Constant scores were significantly higher after 6 months and 2 years after intramedullary stabilization. Patients in the operative group showed a significant improvement of posttraumatic clavicular shortening; they were also more satisfied with cosmetic appearance and overall outcome.\n ESIN of displaced midshaft clavicular fractures resulted in a lower rate of nonunion and delayed union, a faster return to daily activities, and a better functional outcome. Clavicular shortening was significantly lower, and overall satisfaction was higher in the operative group.", "Objective: Studies showed elastic stable intramedullary nailing (ESIN) of displaced midclavicular fractures has excellent outcomes, as well as high complication rates and specific problems. The aim was to discuss ESIN of midshaft clavicular fractures. Methods: Totally 60 eligible patients (aged 18-63 years) were randomized to either ESIN group or non-operative group between January 2007 and May 2008. Clavicular shortening was measured after trauma and osseous consolidation. Radiographic union and complications were assessed. Function analysis including Constant shoulder scores and disabilities of the arm, shoulder and hand (DASH) scores were performed after a 15-month follow-up. Results: ESIN led to a signifcantly shorter time to union, especially for simple fractures. In ESIN group, all patients got fracture union, of which 5 cases had medial skin irritation and 1 patient needed revision surgery because of implant failure. In the nonoperative group, there were 3 nonunion cases and 2 symptomatic malunions developed requiring corrective osteotomy. At 15 months after intramedullary stabilization, patients in the ESIN group were more satisfied with the appearance of the shoulder and overall outcome, and they benefited a lot from the great improvement of post-traumatic clavicular shortening. Furthermore, DASH scores were lower and Constant scores were significantly higher in contrast to the non-operative group. Conclusion: ESIN is a safe minimally invasive surgical technique with lower complication rate, faster return to daily activities, excellent cosmetic and better functional results, restoration of clavicular length for treating mid-shaft clavicular fractures, resulting in high overall satisfaction, which can be regard as an alternative to plate fixation or nonoperative treatment of mid-shaft clavicular fractures.", "We conducted a prospective, randomized study to determine if patients with midshaft clavicle fractures would benefit from immediate operative stabilization with a modified Hagie pin in comparison with a matched group treated with nonoperative therapy. At a level II trauma center, patients with closed midshaft clavicle fractures were prospectively randomized to receive either operative or nonoperative treatment. Fifty-seven (29 operative, 28 nonoperative) patients were enrolled in the study. Operative patients underwent open reduction and internal fixation of the clavicle using a modified Hagie pin; nonoperative patients were treated with a sling for comfort. All patients were followed at regular intervals for 1 year. They were evaluated for radiographic healing and complications and were scored with the Single Assessment Numeric Evaluation and L'Insalata instruments. Injury severities and radiographs were not statistically significantly different between the 2 groups. Functional scores in the operative group were slightly higher at 3 weeks, and the nonoperative group had slightly higher scores at 6 months and 1 year. The only statistically significant difference between the groups was at 3 weeks. Percentage follow-up at 1 year was 93% for the operative group and 82% for the nonoperative group. One patient in each group developed a nonunion, and 1 patient in each group had a refracture. Complications were higher in the operative group, and most were related to pin prominence at the posterior shoulder. Results of this study suggest that, though patients with midshaft clavicle fractures had higher functional scores at short-term follow-up after internal fixation, functional scores were similar at 6 months and 1 year. In addition, internal fixation with a modified Hagie pin was associated with a higher complication rate." ]

[ "2513207", "11679932", "519476", "3934451", "1460700", "11796084", "2499203", "3140683", "3897559", "6738337", "10588768", "3104624", "6401550", "10068597", "3126306", "3938925", "7195257", "7016124", "2508502", "849020", "6882062", "7195247", "12224581" ]

[ "Field trial of the efficacy of a simplified and standard metrifonate treatments of Schistosoma haematobium.", "Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study.", "Praziquantel: a new schistosomicide against Schistosoma haematobium.", "Proteinuria, hematuria, and leukocyturia in children with mixed urinary and intestinal schistosomiasis.", "The impact of Schistosoma haematobium infection and of praziquantel treatment on the growth of primary school children in Bertoua, Cameroon.", "Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective.", "Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya.", "Chemotherapy-based control of schistosomiasis haematobia. I. Metrifonate versus praziquantel in control of intensity and prevalence of infection.", "Treatment with praziquantel of schoolchildren with concurrent Schistosoma mansoni and S. haematobium infections in Gezira, Sudan.", "[Comparison of 3 metrifonate dosages in mass chemotherapy of Schistosoma haematobium].", "The impact of population level deworming on the haemoglobin levels of schoolchildren in Tanga, Tanzania.", "Comparative trials of regimes for the treatment of urinary schistosomiasis in The Gambia.", "Single dose oral treatment in urinary schistosomiasis: a double blind trial.", "Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths.", "Efficacy of low doses of praziquantel for Schistosoma mansoni and S. haematobium.", "Relationships of Schistosoma haematobium, hookworm and malarial infections and metrifonate treatment to growth of Kenyan school children.", "Praziquantel in the treatment of mixed S. haematobium and S. mansoni infections.", "Clinical experience with praziquantel in the treatment of Nigerian patients infected with S. haematobium.", "Single dose metrifonate or praziquantel treatment in Kenyan children. II. Effects on growth in relation to Schistosoma haematobium and hookworm egg counts.", "Field trial of metrifonate in the treatment and prevention of schistosomiasis infection in man.", "A comparative trial of praziquantel, metrifonate and niridazole against Schistosoma haematobium.", "Tolerance and efficacy of praziquantel in phase II A and II B therapeutic trials in Zambian patients.", "Randomized comparison of low-dose versus standard-dose praziquantel therapy in treatment of urinary tract morbidity due to Schistosoma haema tobium infection." ]

[ "In a randomized double-blind study, the percentage egg reduction and cure rate after the standard schedule of metrifonate treatment of Schistosoma haematobium (3 doses of 7.5 mg.kg-1 at two-weekly intervals; A) and an abbreviated regimen (3 doses of 5 mg.kg-1 in one day; B) were compared in five villages in Somalia. 300 patients who were excreting 20 or more eggs of S. haematobium in 10 ml urine were recruited. The patients were classified according to their home villages and were then, randomly allocated to treatment A or B. They had similar ages, weights and egg output. Each patient received 3 doses of metrifonate and 2 doses of identical appearing placebo. Group A received metrifonate on the 1st, 4th and 5th dosing occasions and placebo on the 2nd and 3rd times. Group B received metrifonate on the 1st, 2nd and 3rd dosing times and placebo on the 4th and 5th times. Two hundred and one patients were followed up from 1 to 6 months. The remaining 99 (33%) patients either did not complete treatment or were lost during follow up. Egg reduction in the groups 1, 2, 3 and 6 months after treatment were 97, 97, 95 and 93% in Group A and 96, 96, 94 and 92% in Group B (NS). Corresponding cure rates for Group A were 52, 50, 48 and 44%, and in Group B they were 47, 48, 43 and 40% (NS). Seven patients from Group A and 9 from Group B complained of minor side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)", "Recently, artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections. Therefore, a double-blind, randomized, placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon. The 300 infected schoolchildren included in the study were randomized to receive artesunate plus placebo (n=90), praziquantel plus placebo (n=90), artesunate and praziquantel (n=90), or only placebo (n=30). End points were efficacy, assessed as cure on day 56, and tolerability. All treatment regimens were well tolerated. The praziquantel plus placebo-treated group attained a cure rate of 73%, artesunate plus placebo a rate of 27%, the combination of artesunate and praziquantel a rate of 81%, and placebo alone a rate of 20%. In summary, earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections.", "The effectiveness of the new schistosomicide praziquantel was assessed in African schoolchildren infected with Schistosoma haematobium. They were stratified according to the severity of their infection and were then randomly allocated to treatment with two single-dose regimens (30 and 40 mg/kg) and a split regimen of two doses of 20 mg/kg given four hours apart. All three regimens were highly effective and produced few side effects. Children who initially had very high pretreatment egg loads showed a poorer therapeutic response at all dose levels, and further investigations are necessary to find the optimum dose. Because of its effectiveness in a single dose and lack of toxicity, praziquantel may prove to be the ideal schistosomicide.", "Quantitative parasitological assessment and quantitative analysis of proteinuria, hematuria, and leukocyturia were carried out in 182 Sudanese schoolboys with mixed urinary and intestinal schistosomiasis. Pathological proteinuria was found in 73% of patients (median = 380, 95% confidence limits = 200 to 500 mg/liter). The median protein/creatinine ratio was 0.54. SDS polyacrylamide gel electrophoresis showed an excretion of albumin, transferrin, and IgG consistent with a postrenal pattern of proteinuria. Pathological erythrocyturia occurred in 84% of patients (median = 255, 95% CL = 95 to 629 cells/microliter) and leukocyturia in 77% of patients (median = 148, 95% CL = 93 to 246 cells/microliter). Phase contrast microscopy revealed intact erythrocytes, suggestive of postrenal hemorrhage. Proteinuria, erythrocyturia, and leukocyturia correlated significantly with the ova excretion in the urine, but not with egg excretion in the stool. Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings. In patients treated effectively with Praziquantel or Metrifonate, pathological PU, EU, and LU decreased markedly 1 month post treatment. PU in severely proteinuric patients reached physiological values 5 months post therapy. We suggest that the proteinuria, erythrocyturia, and leukocyturia in mixed schistosomiasis were of postrenal origin.", "Our objective was to determine in a Cameroonian school population the effect of mild to moderate S. haematobium infection intensity on growth and development of children before and 6 months after praziquantel treatment. Previous studies have yielded contradictory results. Children from Bertoua schools were divided into four study groups: heavily infected (> 500 eggs 10 ml-1), moderately infected (1-499 eggs 10 ml-1) treated with praziquantel, a similar group treated with placebo, and an uninfected control group. Anthropometric measures--height for age per cent median (HAPM), and weight for age per cent median (WAPM)--were significantly higher among the uninfected children. Stepwise regression analysis showed that S. haematobium and Ascaris infections were the strongest predictors of the HAPM with hookworm and malaria infections playing a lesser role. Post treatment comparison of the praziquantel treatment group and the placebo group showed no significant differences for the anthropometric indicators except for mid-arm circumference. Longer observations of growth after treatment as well as monitoring of the rate of reinfection would be necessary to understand better the effect of S. haematobium on growth.", "To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal. To assess the South African government's parasite control policy.\n The study recruited 268 school children, aged 8 to 10, and randomly allocated them into treatment and placebo groups (treatment consisted of a single dose of albendazole (400 mg) and praziquantel (40 mg/kg)). Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline (prior to treatment) and 16 weeks post treatment. Two weeks after treatment prevalence and intensity were again measured for an approximate 50% sub-sample of the children to investigate efficacy of treatment. An analysis of the South African government's policies concerning parasite control is assessed in the light of these epidemiological findings.\n Low levels of both stunting and wasting were observed throughout the study (approximately 10% and 1%, respectively), but did not vary significantly across either treatment group or time period (P >0.50). At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5%, Trichuris trichiura 51.9% and Schistosoma haematobium 22.3%. These prevalences declined significantly to 4.7% (P <0.0005), 38.0% (P < 0.03), and 3.3% (P < 0.0002), respectively, 16 weeks post treatment. The majority of infections observed at baseline were of light intensity, namely A. lumbricoides (50%), T. trichiura (80%) and S. haematobium (100%), and following treatment these levels were reduced significantly (P <0.0001, P< 0.05 and P < 0.005, respectively). The levels of both prevalence and intensity in the untreated group remained constant. The cure rates over the first two weeks of the study were found to be 94.4% for A. lumbricoides, 40% for T. trichiura and 72.2% for S. haematobium.\n The benefits of targeted, school-based treatment in reducing the prevalence and intensity of infection supports the South African government's focus of using school-based interventions as part of an integrated parasite control programme. These strategies and programmes are consistent with recommendations of the World Health Organization (WHO) and The United Nations Children's Fund (UNICEF).", "To assess the efficacy of low dose praziquantel regimens in comparison with standard 40 mg/kg dosing in the treatment of urinary schistosomiasis, a random allocation dose-finding trial was performed in children and adults from a Schistosoma haematobium endemic region in Coast Province, Kenya. Following an initial screening, 280 individuals with greater than or equal to 50 eggs/10 ml urine were randomly assigned to receive either 10, 20, 30, or 40 mg/kg of the drug in a single oral dose. Two to three months later, cure rates of 26%, 68%, 78%, and 84% were found for the 10, 20, 30, and 40 mg/kg doses, respectively. The results of 10 mg/kg oral dosing were significantly worse than for all other doses in terms of cure rate and of post-treatment prevalence of morbidity. The 40 mg/kg dosing resulted in a significantly higher cure rate than the 20 mg/kg doses; nevertheless, there was no significant difference between 20 mg/kg and 40 mg/kg doses in terms of mean post-treatment intensity of infection or post-treatment prevalence of hematuria or proteinuria. For large-scale control programs, oral 20 mg/kg praziquantel therapy for urinary schistosomiasis may prove as effective as the standard oral 40 mg/kg dosing for control of infection-associated morbidity and reduction of parasite transmission.", "To determine the effect of targeted field administration of oral chemotherapeutic agents on the prevalence, intensity, and morbidity of Schistosoma haematobium infections, we initiated a long-term school-based program in the Msambweni area of Kwale District, Coast Province, Kenya. Prior to treatment, 69% of the children examined (ages 4-21, n = 2,628) were infected; 34% had moderate or heavy infections (greater than 100 eggs/10 ml urine). Infected individuals were randomized to receive, during one year, either metrifonate (10 mg/kg x 3 doses) or praziquantel, (40 mg/kg x 1 dose). At the end of the first year, prevalence of infection fell to 19%; only 2% of the pupils remained in the moderately and heavily infected groups. Corresponding decreases in the prevalence of hematuria (54% in 1984 vs. 16% in 1985) and proteinuria (56% in 1984 vs. 26% in 1985) were noted. These were associated with significant declines in bladder thickening and irregularities noted during ultrasound examinations, but not with decreases in hydronephrosis. There was no significant difference in the post-treatment prevalence or intensity of infection after treatment with metrifonate as compared with praziquantel. These results demonstrate that field-applied chemotherapy with either agent offers a practical strategy for the control of S. haematobium infection and its associated morbidity.", "A field trial was conducted in Sudan to evaluate the acceptability and efficacy of praziquantel given to schoolchildren aged 7-11 years who were all infected with both Schistosoma mansoni and S. haematobium. Two dosage regimes were compared, a single dose of 40 mg/kg bodyweight, and a divided dose 2 X 20 mg/kg given 4-6 h apart. When interviewed 24 h after treatment, 80% of the children complained of drug-induced abdominal pain, diarrhoea, nausea or vomiting. However none of the side-effects persisted beyond the day of treatment. More children complained of side-effects from the divided dose than from the single dose. The cure rate in the divided-dose group was slightly better than in the single-dose group but the differences were not significant at any follow-up, nor when results were expressed in terms of cumulative failures. The initial cure rates were 66.3% and 61.8% at 1 month, and 73.2% and 64.7% at 3 months for the divided and single doses respectively. After 12 months there had apparently been considerable reinfection with S. mansoni and 73% of the children were passing eggs. Reinfection with S. haematobium was negligible.", "The metrifonate standard cure consisted of three doses of 7.5 to 10 mg/kg at a fortnight interval. These repeated doses increase the total cost of the treatment and the number of incomplete cures. We wanted to verify whether a reduced cure gets still a good efficacy. 286 people from three villages situated near Niamey (Niger) where treated at random with either 1, 2 or 3 doses of 10 mg/kg metrifonate. Before treatment the mean egg-output was 40 eggs/10 ml; 4 months later the cure rate was different only between the 1 dose trial and the 3 doses one. Moreover, this rate is low (35.3%) and the mean egg-output is also low (40.3%) for one dose. These results are more significant according to the first mean egg-output level. Below 5 eggs/10 ml, the cure rate is good with 2 or 3 doses (62% and 70%, 4 months later treatment), between 6 and 50 eggs/10 ml the results are still acceptable (55 and 53%). On the other hand, above 50 eggs these results are insufficient even with 3 doses. The single dose does not give sufficient result even in low egg-output.", "The impact of albendazole (400 mg) and praziquantel (40 mg/kg body weight) treatment of schoolchildren was compared with placebo according to the presence of anaemia (haemoglobin concentration < 11. 0 g/dl) and heavy (> 5000 epg) or light (< 5000 epg) hookworm egg load. The study was conducted in rural Tanga. Medication was administered in September 1994 and children were followed-up in January 1995. Overall, anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group (- 0.11 g/dl vs. - 0.35 g/dl; P = 0.02). Anthelminthic treatment was of greatest benefit to the 9% of children with both anaemia and heavy hookworm egg load (+ 0.67 g/dl vs. - 0.67 g/dl) and was also of significant benefit to the 38% of children with anaemia and light hookworm egg load (+ 0.07 g/dl vs. - 0.21 g/dl). It was of no significant benefit to children who were not anaemic. This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths (37% of total population).", "Alternative regimes for the treatment of Schistosoma haematobium infection were compared in two trials. Praziquantel at a dose of 40 mg kg-1 appeared to cure 63% of a random sample of heavily infected subjects; significantly more than the 18% cured by three fortnightly doses of metrifonate at 10 mg kg-1. However, praziquantel led to a greater incidence of mild, transient side-effects. A single dose of metrifonate was found to be an inadequate treatment in the same group of subjects as it left 53% with an egg count of at least 100 ova/10 ml. A combination of 10 mg kg-1 of metrifonate and 25 mg kg-1 of niridazole had a similar effect to that of a single dose of metrifonate alone and it had more side-effects. Reduced doses of praziquantel had less effect on egg counts than the standard regime, but the difference was not significant in the case of 20 mg kg-1. Although a combination of metrifonate and praziquantel, each at 10 mg kg-1, had a greater effect than either constituent alone, the difference was not significant. Factors affecting the choice of drug for use in mass treatment of urinary schistosomiasis in The Gambia are discussed. The present findings suggest that the standard regime of praziquantel should be used or, if this is not possible, a three-dose metrifonate regime.", "A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren; selection was biased towards those who excreted large quantities of eggs. Praziquantel 40 mg/kg was the most effective drug giving a greater than 97% reduction in egg output six months after treatment; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92% and metrifonate 10 mg/kg alone a reduction of greater than 86%. Fewer children continued to have moderate to heavy infections (excretion greater than 124 ova/10 ml urine) six months after treatment with praziquantel (5%) and the combined regimen (7%) than with metrifonate (16%). Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection, the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective.", "A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis. The study sites were in China and the Philippines, including 2 strains of Schistosoma japonicum, and 2 different regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma haematobium. Neither medication affected the cure rate of the other. There was no difference between the side effect rate from albendazole or the double placebo. Praziquantel-treated children had more nausea, abdominal pain, and headache but these side effects were statistically more common in children with schistosomiasis, suggesting a strong influence of dying parasites. The subjects were followed for 6 months for changes in infection status, growth parameters, hemoglobin, and schistosomiasis morbidity. In all 4 sites, a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel, strongly supporting population-based mass treatment.", "The shortage of available information on the impact of low doses of praziquantel was remedied by a trial of 0, 10, 20, 30 and 40 mg kg-1 against double infections of Schistosoma haematobium and S. mansoni in a rural area of Zimbabwe. No significant differences were found in egg reduction between 20-40 mg kg-1 for S. haematobium and between 30-40 mg kg-1 for S. mansoni. It is suggested that morbidity control can be achieved with lower dosages of praziquantel than currently recommended.", "Relationships of S. haematobium, hookworm and malarial infections to growth 6 months after metrifonate treatment were studied in Kenyan primary school children in an area where poor growth, S. haematobium and hookworm were common and malaria was endemic. All children with light-moderate S. haematobium infections (1-500 eggs/10 ml adj) in 4 schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 201) groups, treated, and examined again 6 months later (Exam 2). An additional 19 heavily infected children (HIT group greater than 500 eggs/10 ml adj) were treated immediately after Exam 1 and also followed. The MIT and HIT groups exhibited more rapid growth between Exam 1 and 2 than did the placebo group. The MIT group gained significantly (P less than 0.001) more than the MIP group in weight (0.8 kg), percent weight for age (2.3 percentage points), weight for height squared (0.04 units), arm circumference (0.4 cm), percent arm circumference for age (1.7 percentage points) and in triceps and subscapular skinfold thicknesses. In addition, the placebo group showed statistically significant decreases between exams in percentage weight for age, percent arm circumference for age, both skinfold thicknesses for age and no significant increase in percent height for age while the MIT group exhibited highly significant increases in all anthropometric parameters.(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomized single blind stratified study involving 153 patients with mixed S. mansoni and S. haematobium infection showed that 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) is effective in giving high cure rates in each infection separately, 66% (64 patients) and 77% (94 patients), respectively. The complete clearance of both infections (i.e., no eggs whether dead or alive) 6 months after treatment was 29% (43 patients). The side effects of the drug were minimal and transient, the most common being gastrointestinal ones. The assessment of the objective tolerability by clinical, haematological and biochemical tests showed also that the drug was very safe. It is thus concluded that the drug is a promising useful tool in the control of schistosomiasis in general and the treatment of the individual.", "A double-blind controlled trial of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a] isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) in the treatment of vesical schistosomiasis has been carried out in 90 Nigerian schoolchildren of both sexes aged 9--16 years. Oral doses of 1 x 30, 1 x 40, and 2 x 20 mg/kg b.w. were assessed against placebo at 1 x 40 mg/kg, and the subjects followed up for up to twelve months after treatment. The results showed that the drug is very effective against S. haematobium infections and well tolerated. There were not significant differences between the three dosage groups, and the drug had no adverse haematological or biochemical effects. It is concluded that praziquantel widely meets the requirements necessary for use in large scale control of vesical schistosomiasis.", "We studied the growth of comparable groups of children with light to moderate Schistosoma haematobium infections who received a single dose of metrifonate (MT, 10 mg/kg), praziquantel (PR, 40 mg/kg), or a placebo (PL). Children were re-examined 8 months later. The MT and PR groups gained significantly more than the placebo group in weight, percent weight for age, percent weight for height, arm circumference, and in triceps and subscapular skinfold thicknesses. The MT and PR groups did not differ significantly from each other. The placebo group showed statistically significant decreases or no change between exams in percent weight for age, percent weight for height, percent arm circumference, and both skinfold thicknesses; the MT and PR groups exhibited highly significant increases in these parameters (P less than 0.0002). The intensity of S. haematobium infection had decreased significantly in both the MT and PR groups, but especially in the PR group. Multiple regression analyses showed that a decrease in the intensity of S. haematobium infection was by far the most important predictor of growth rate after treatment for all 5 anthropometric measures tested; decreases in the intensity of hookworm infection was also significant for 2 of the 5 measures.", "A field trial was set up to test the prophylactic properties of the organophosphorous drug metrifonate (Bilarcil Bayer AG). Subjects were rural African children living in an area of Rhodesia where Schistosoma haematobium and S. mansoni are highly endemic. The trial was conducted in three stages, a preliminary period of therapy followed by two six-month periods of prophylaxis. Parasitological and haematological tests were carried out monthly and major assessments (including clinical examinations) were carried out prior to the start of the trial and at the end of each of the three stages. Drug was given to the appropriate groups at a dose rate of 7-5 mg/kg once per fortnight for three doses during the therapy stage and four-weekly during the prophylaxis stage. Results with S. haematobium were very good. A 60% cure-rate was observed six weeks aection was obtained in those children continuing to receive the drug as a prophylactic, even during the season of highest transmission; intensities of infection in those who became infected were very low. Infection rates in the treated but unprotected group rose steadily from 40% at week 11 to 95% at week 70. There was a sigificant effect upon the intensity of S. mansoni infections only when pre- and post-trial data were compared. Apart from the anticipated (and previously reported) depression of plasma cholinesterase values no side effects were recorded. Drug tolerance and acceptibility were very high. It is likely that the costs of a year's protection against S. Haematobium using metrifonate will be significantly lower than protection by molluscicidal techniques or single courses of treatment with established drugs.", "Praziquantel administered in a single oral dose of 30 mg kg-1 to subjects infected with Schistosoma haematobium produced minimal side effects and was more effective than established regimes of niridazole and metrifonate. Praziquantel should prove a major tool in schistosomiasis control programmes.", "nan", "At present, anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body weight is the recommended treatment for control of urinary tract morbidity caused by Schistosoma haematobium. Although this standard regimen is effective, drug cost may represent a significant barrier to implementation of large-scale schistosomiasis control programs in developing areas. Previous comparison trials have established that low-dose (20-30 mg/kg) praziquantel regimens can effectively suppress the intensity of S. haematobium infection in endemic settings. However, the efficacy of these low-dose regimens in controlling infection-related morbidity has not been determined in a randomized field trial. The present random allocation study examined the relative efficacy of a 20 mg/kg dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder and renal abnormalities associated with S. haematobium infection in an endemic area of Coast Province, Kenya. After a nine-month observation period, the results indicated an advantage to the standard 40 mg/kg praziquantel dose in terms of reduction of infection prevalence and hematuria after therapy (P < 0.01 and P < 0.005, respectively). However, the two treatment groups were equally effective in reducing structural urinary tract morbidity detected on ultrasound examination. We conclude that in certain settings, a 20 mg/kg dose of praziquantel may be sufficient in providing control of morbidity due to urinary schistosomiasis in population-based treatment programs." ]

[ "19121589", "12783106", "12669122", "15878544", "8661630", "11137927", "16444853", "11057850", "12706636", "10436448", "9974369", "19635277", "17208082", "7831650" ]

[ "A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.", "Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism.", "Low-molecular-weight heparin in the acute and long-term treatment of deep vein thrombosis.", "Long-term treatment of deep venous thrombosis with a low molecular weight heparin (tinzaparin): a prospective randomized trial.", "Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial.", "Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis.", "Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism.", "Low molecular weight heparin (enoxaparin) versus oral anticoagulant therapy (acenocoumarol) in the long-term treatment of deep venous thrombosis in the elderly: a randomized trial.", "An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.", "Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.", "Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis.", "Home therapy of venous thrombosis with long-term LMWH versus usual care: patient satisfaction and post-thrombotic syndrome.", "Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.", "Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis." ]

[ "To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).\n A randomised, open-label trial.\n In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.\n During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.\n Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.", "Conventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a \"bridge\" to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy. We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a \"bridge\" to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily. In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.", "Low molecular weight heparins (LMWHs) are frequently used during acute treatment of deep vein thrombosis, but their utility for long-term treatment needs to be defined. In this multi-centre trial, 378 patients with acute deep vein thrombosis were randomised to intravenous unfractionated heparin (group A), once daily subcutaneous LMWH (bemiparin) for one week (group B) or once daily bemiparin in a therapeutic dose for one week followed by a maintenance dose for 12 weeks (group C). Fifty-two per cent of patients in group A, 72% of group B and 72% of group C showed venographic reduction in thrombus size assessed objectively on day 14; 20% greater improvement in group B and C indicates not only non-inferiority of bemiparin (p = 0.00003) but also superiority (p = 0.004) compared to UFH. Day 84 venographic or Doppler sonographic recanalisation of the affected veins was demonstrated in 75.3%, 79.8% and 81.5% in groups A, B and C respectively. Mortality, recurrent thromboembolic events and bleeding were similar in the three groups. Both bemiparin regimens were more effective than UFH in reducing thrombus size during the acute phase of treatment. The efficacy in terms of recurrence of venous thromboembolism and safety of Bemiparin is similar to UFH. Bemiparin is also an effective alternative to warfarin for long-term treatment.", "Evaluation of the effectiveness and safety of the low molecular weight heparin (LMWH) tinzaparin versus unfractionated heparin (UFH) followed by acenocoumarol in proximal deep venous thrombosis (DVT).\n Prospective, randomized clinical trial.\n Consecutive patients (n=108) with acute leg DVT, confirmed by duplex, were randomized to either tinzaparin alone or UFH and acenocoumarol for 6 months. Patients were evaluated ultrasonographically at entry, 1, 3, 6 and 12 months. Thrombus regression, reflux distribution and the incidence of complications were studied. A cost-analysis, comparing the two treatments, was performed.\n The overall incidence of major events (mortality, DVT recurrence, pulmonary embolism, major bleeding, heparin-induced thrombocytopenia) was significantly different (p=0.035) in favor of tinzaparin (7 versus 17 events). The ultrasonographic clot volume score (an index of recanalization) decreased significantly in both treatment groups. However, tinzaparin produced significantly more extended overall recanalization from 3 months onwards (p<0.02). Thrombus regression was equivalent or in favor of tinzaparin in the different DVT subgroups and venous segments, but the statistical significance varied. Reflux showed non-significant differences overall or in subgroups. A cost-analysis resulted in favor of LMWH.\n A fixed daily dose of tinzaparin for 6 months was at least as effective and safe as UFH and acenocoumarol. Regarding major events and recanalization, there was a significant benefit in favor of tinzaparin. Long-term DVT treatment with tinzaparin could represent an alternative to conventional treatment.", "A group of 105 consecutive patients with venographically proved major acute deep vein thrombosis (DVT) were randomized in an open prospective study to evaluate the comparative efficacy and safety of a fixed dose of subcutaneous low-molecular-weight heparin (LMWH) and warfarin for the prevention of recurrent venous thromboembolism. Four patients developed venographically proved recurrent DVT during the 3 months of treatment: three in the LMWH group and one in the warfarin group. Nonfatal pulmonary embolism occurred in two patients in the LMWH group and in one in the warfarin group. Five of the 55 patients (10%) in the warfarin group and none of the 50 patients in the LMWH developed bleeding complications (two-tailed Fisher exact test, p = 0.06). A preliminary assessment of the costs indicated that treatment with LMWH was less expensive by Pounds 900 per patient than warfarin. In conclusion, the fixed daily dose of LMWH and the adjusted dose of warfarin therapy were of similar efficacy in preventing recurrence of DVT. However, warfarin therapy, despite strict laboratory control, is associated with more frequent side effects and is expensive. Another study with a higher dose of LMWH is recommended.", "The purpose of this study was to evaluate whether low molecular weight heparin (LMWH) could be equal or more effective than conventional oral anticoagulants (OAs) in the long-term treatment of deep venous thrombosis (DVT).\n One hundred fifty-eight patients with symptomatic DVT of the lower limbs confirmed by means of duplex ultrasound scan were randomized to receive 3 to 6 months' treatment with nadroparine calcium or acenocoumarol. Quantitative and qualitative duplex scan scoring systems were used to study the evolution of thrombosis in both groups at 1, 3, 6, and 12 months.\n During the 12-month surveillance period, two (2.5%) of the 81 patients who received LMWH and seven (9%) of the 77 patients who received OAs had recurrence of venous thrombosis (not significant). In the LMWH group no cases of major bleeding were found, and four cases (5.2%) occurred in the OA group (not significant). The mortality rate was nine (11.1%) in the LMWH group and 7.8% in the OA group (not significant). The quantitative mean duplex scan score decreased in both groups during the follow-up and had statistical significance after long-term LMWH treatment on iliofemoral DVT (1, 3, 6, and 12 months), femoropopliteal DVT (1-3 months), and infrapopliteal DVT (first month). Duplex scan evaluation showed that the rate of venous recanalization significantly increased in the common femoral vein at 6 and at 12 months and during each point of follow-up in the superficial and popliteal veins in the LMWH group. Reflux was significantly less frequent in communicating veins after LMWH treatment (17.9% vs 32.2% in the OA group). The reflux rates in the superficial (22.4% in the LMWH group, 30.6% in OA group) and deep (13.4% vs 17.7%) venous system showed no significant differences between groups.\n The unmonitored subcutaneous administration of nadroparine in fixed daily doses was more effective than oral acenocoumarol with laboratory control adjustment in achieving recanalization of leg thrombi. With nadroparine, there was less late valvular communicating vein insufficiency, and it was at least as efficacious and safe as oral anticoagulants after long-term administration. These results suggest that LMWHs may therefore represent a real therapeutic advance in the long-term management of DVT.", "We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) (n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/- 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.", "This study aims to establish the relative effectiveness and safety of low molecular weight heparin in elderly patients with venous thrombosis in order to find an alternative to oral anticoagulant therapy with less bleeding complications in the long-term treatment of deep venous thrombosis (DVT). One hundred consecutive elderly patients (>75 years old) with venographically demonstrated proximal DVT were included in a randomized trial. All patients were treated for ten days with adjusted doses of intravenous heparin. Informed consent was obtained and on the eight day, patients were randomly allocated to receive acenocoumarol (INR 2.0-3.0) or subcutaneous enoxaparin (4000 anti-Xa units once a day) for three months. All patients were followed-up clinically and venographically for a one year period. The results were analyzed with Fisher's exact test or chi-square test as appropriate. During the treatment and surveillance period, 6 of the 50 patients (12%) who received acenocoumarol and 8 of the 50 patients (16%) who received enoxaparin had new episodes of venous thromboembolism confirmed by objective testing (p = 0.6; 95% CI for the difference: -19.5 to 11.5). Hemorrhagic complications occurred in six of the 50 patients (12%) who received acenocoumarol and in one (2%) of those on enoxaparin (p = 0.1; 95% CI for the difference: -1.8 to 21.8). Vertebral fractures developed in 2 patients (4%) in the enoxaparin group (p = 0.5; 95% CI for the difference: -11.4 to 3.4). These results show that fixed dose enoxaparin seems to be effective and safe in the long-term treatment of proximal DVT in the elderly. In comparison with oral anticoagulants, the findings are inconclusive due to the wide confidence intervals for differences between outcomes, however they suggest that the former may have less bleeding complications with similar efficacy.", "Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children.\n This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely.\n At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group.\n Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.", "The primary objective of this study was to evaluate with venography the rate of thrombus regression after a fixed dose of low-molecular weight heparin (LMWH) per day for 3 months compared with oral anticoagulant therapy for deep venous thrombosis (DVT). Secondary endpoints were the comparisons of the efficacy and safety of both treatments.\n This study was designed as an open randomized clinical study in a university hospital setting. Of the 165 patients finally enrolled in the study, 85 were assigned LMWH therapy and 80 were assigned oral anticoagulant therapy. In the group randomized to oral anticoagulant therapy, the patients first underwent treatment in the hospital with standard unfractionated heparin and then coumarin for 3 months. Doses were adjusted with laboratory monitoring to maintain the international normalized ratio between 2.0 and 3.0. Patients in the LMWH group were administered subcutaneous injections of fixed doses of 40 mg enoxaparin (4000 anti-Xa units) every 12 hours for 7 days, and after discharge from the hospital, they were administered 40 mg enoxaparin once daily at fixed doses for 3 months without a laboratory control assay. A quantitative venographic score (Marder score) was used to assess the extent of the venous thrombosis, with 0 points indicating no DVT and 40 points indicating total occlusion of all deep veins. The rate of thrombus reduction was defined as the difference in quantitative venographic scores after termination of LMWH or coumarin therapy as compared with the scores obtained on the initial venographic results. The efficacy was defined as the ability to prevent symptomatic extension or recurrence of venous thromboembolism (documented with venograms or serial lung scans). The safety was defined as the occurrence of hemorrhages.\n After 3 months of treatment, the mean Marder score was significantly decreased in both groups in comparison with the baseline score, although the effect of therapy was significantly better after LMWH therapy (49.4% reduction) than after coumarin therapy (24.5% reduction; P <.001). LMWH therapy and male gender were independently associated with an enhanced resolution of the thrombus. A lower frequency of symptomatic recurrent venous thromboembolism was also shown in patients who underwent treatment with LMWH therapy (9.5%) than with oral anticoagulant therapy (23.7%; P <.05), although this difference was entirely a result of recurrence of DVT. Bleeding complications were significantly fewer in the LMWH group than in the coumarin group (1. 1% vs 10%; P <.05). This difference was caused by minor hemorrhages. Coumarin therapy and cancer were independently associated with an enhanced risk of complications. Subcutaneous heparin therapy was well tolerated by all patients.\n The patients who were allocated to undergo enoxaparin therapy had a significantly greater improvement in their quantitative venographic score, a significantly lower recurrence rate of symptomatic venous thromboembolism, and a significantly lower incidence of bleeding than patients who underwent treatment with coumarin. LMWH can be used on an outpatient basis as a safer and more effective alternative to classical oral anticoagulant therapy for the secondary prophylaxis of selected patients with DVT.", "The aim of this study was to determine the efficacy and safety of subcutaneous weight-adjusted dose low molecular weight heparin (LMWH) compared with oral anticoagulant (OA) in the prevention of recurrent venous thromboembolism. In a prospective multicenter trial, 202 patients with symptomatic proximal deep vein thrombosis (DVT) were included. As soon as the diagnosis of DVT was confirmed by phlebography, 101 were randomly assigned to receive LMWH (nadroparin) for secondary prophylaxis and 101 to receive OA (acenocoumarol). Patients in both groups were initially treated with nadroparin in a dose of 85 anti-Xa IU/kg s.c. every 12 h. Secondary prophylaxis with either nadroparin, 85 anti-Xa IU/kg s. c. once daily, or acenocoumarol was continued for at least 3 months. Three patients in the LMWH group and 6 in the OA group were excluded from analysis for various reasons. During the one-year combined secondary prophylaxis and surveillance period, 7 of of the 98 evaluable patients (7.1%) in the LMWH group and 9 of the 95 evaluable patients (9.5%) in the OA group had a documented recurrence of venous thromboembolism (Fisher's exact test, p = 0.61). Of these, 2 patients who received LMWH and 7 patients on acenocoumarol had recurrences in the 3-month period of secondary prophylaxis. Four patients (4.1%) in the LMWH group developed bleeding complications during this study period, as compared with 7 (7.4%) in the OA group (Fisher's exact test, p = 0.37). There were two major bleedings, one in the LMWH group and one in the OA group. Eleven patients died, 5 (5.1%) in the LMWH group and 6 (6.3%) in the OA group. It is concluded that nadroparin in a dose of 85 anti-Xa IU/kg s.c. once daily provides an effective and safe alternative to oral anticoagulants in the secondary prophylaxis of DVT.", "Home-LITE compared long-term treatment at home with tinzaparin or usual care in terms of efficacy, safety, patients' treatment satisfaction, incidence of post-thrombotic syndrome, and associated venous leg ulcers.\n This multicenter, randomized, controlled trial enrolled 480 patients with documented, acute, proximal deep vein thrombosis. Patients received tinzaparin 175 IU/kg subcutaneously once daily for 12 weeks, or tinzaparin for >or=5 days plus oral warfarin, commenced on day 1, international normalized ratio-adjusted, and continued for >or=12 weeks (\"usual care\"). Patients received 1 in-clinic injection, then home treatment.\n The rate of recurrent venous thromboembolism at 12 weeks was 3.3% in both groups (absolute difference 0%; 95% confidence interval -3.2-3.2), and at 1 year was 10.4%/8.3% in the tinzaparin/usual-care groups, respectively (difference 2.1%; 95% confidence interval -3.1-7.3). There were no between-group differences in deaths at 12 weeks or 1 year, or bleeding at 12 weeks. Patients in the tinzaparin group expressed significantly greater treatment satisfaction (P = .0024), particularly regarding freedom from the inconvenience of blood monitoring; were less likely to report signs/symptoms of post-thrombotic syndrome (individual odds ratios 0.66 to 0.91, overall odds ratio 0.77, P = .001); and reported fewer leg ulcers at 12 weeks: 1 (0.5%) versus 8 (4.1%) (P = .02) with usual care.\n Long-term home treatment with tinzaparin or usual care resulted in similar rates of recurrent venous thromboembolism, death, and bleeding. The significantly lower incidence of post-thrombotic syndrome and leg ulcers observed in the tinzaparin group is a potentially important benefit and deserves further study.", "A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis.\n We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months.\n Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH.\n Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.", "To evaluate the role of low-molecular weight heparin (LMWH) as an alternative to oral anticoagulants in the prevention of recurrent venous thromboembolism, we compared in a randomized trial conventional warfarin treatment with a three-month course of enoxaparin 4000 anti-Xa units once a day subcutaneously. 187 patients with symptomatic deep-vein thrombosis (DVT), diagnosed by strain-gauge plethysmography plus D-dimer latex assay and confirmed by venography in most cases, were treated with full-dose subcutaneous heparin for ten days and then randomized to secondary prophylaxis. During the 3-month treatment period, 6 of the 93 patients who received LMWH (6%) and 4 of the 94 patients on warfarin (4%) had symptomatic recurrence of venous thromboembolism confirmed by objective testing (p = 0.5; 95% confidence interval [CI] for the difference, -3% to 7%). Four patients in the LMWH group had bleeding complications as compared with 12 in the warfarin group (p = 0.04; 95% CI for the difference, 4% to 14%). In the 9-month follow-up period, during which 34 patients on warfarin prolonged treatment for other 3 months and 14 up to one year, 10 patients in the enoxaparin group and 4 patients in the warfarin group suffered a documented recurrence of venous thromboembolism. Of these 14 late recurrences, just one occurred in patients with postoperative DVT. After one year there were 16 recurrences (17%) in the LMWH group and 8 (9%) in the warfarin group (p = 0.07; 95% CI for the difference, 1% to 16%).(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "12747190", "10884499", "4562221", "2095610", "7510599", "7691481", "5551770", "8454476", "9701421", "9377957", "8688342", "10573224", "17309176", "17998689" ]

[ "Treatment of interstitial peumopathy by fei tong oral liquid in the malignant tumor patients after radio- and/or chemotherapy.", "High-dose rate brachytherapy of bronchial cancer: treatment optimization using three schemes of therapy.", "[Clinical study of the activity and tolerance of hydropropizine, a drug with antitussive activity].", "Comparative evaluation of the antitussive activity of butamirate citrate linctus versus clobutinol syrup.", "Prolonged survival after high-dose rate endobronchial radiation for malignant airway obstruction.", "High dose-rate intraluminal irradiation in bronchogenic carcinoma. Technique and results.", "[Clinical considerations on a new antitussive agent].", "Remote afterloading brachytherapy for the local control of endobronchial carcinoma.", "Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer.", "Local determinants of response to endobronchial high-dose rate brachytherapy in bronchogenic carcinoma.", "Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients.", "Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction.", "Combination of interventional pulmonology techniques (Nd:YAG laser resection and brachytherapy) with external beam radiotherapy in the treatment of lung cancer patients with Karnofsky Index < or =50.", "Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study." ]

[ "Fei Tong Kou Fu Ye ([symbol: see text]) Fei Tong Oral Liquid) was used to treat 30 cases of interstitial pneumopathy after radio- and/or chemotherapy. In comparison with the control group (15 cases) treated with hormones, the therapeutic effects in improving dyspnea, cough, respiratory rate, cyanosis, findings in X-films and CT examination, partial pressure of oxygen in artery, FVC and VC were found significantly better (P < 0.05). The total effective rate obtained was 83.33%.", "Our aim is to demonstrate that a fractionated high-dose rate endobronchial brachytherapy (HDRBT) treatment is tolerable for patients with advanced (IIIA-IIIB) non-small cell lung cancer and gives an improvement of symptoms. Patients and Methods. From January 1992 to July 1997, we treated 320 patients with external beam radiotherapy (EBRT) and concomitant HDRBT with Ir192. Eighty-four patients received 10 Gy in one fraction from January 1992 to March 1993 (Group A); 47 patients received two fractions of 7 Gy each from April 1993 to December 1993 (Group B), and 189 patients received three fractions of 5 Gy each from January 1994 to July 1997 (Group C).\n Mean survival from diagnosis is 11.1 months and mean survival from last HDRBT is 9.7 months. The symptomatic response rate is 90% for dyspnea, 82% for cough, 94% for hemoptysis and 90% for obstructive pneumonia. Performance status was improved in 70% of patients. Follow-up is in the range of 5-36 months with 280/320 evaluable patients (87.5%) (40 patients were lost to follow-up). For the patients treated with three fractions of HDRBT plus EBRT, a smaller number of side effects occurred while relief from symptoms linked to bronchial obstruction and survival was similar for the three groups.\n A three-fraction brachytherapy results in fewer side effects, such as bronchial fibrosis with or without stenosis, while survival and symptomatic relief are similar in the three groups treated.", "nan", "In a double-blind randomized study 60 patients with either irritative cough due to seasonal respiratory disorders or chronic cough of any etiology were treated with either butamirate citrate linctus (Sinecod, Zyma) or with clobutinol syrup (Silomat, Boehringer, Ingelheim) for a period of 5 days at a dose regimen of 3 tablespoons daily. Efficacy was assessed based on the reduction of the severity as well as frequency of the cough and on the global opinion of the physician. Both groups showed highly significant improvements for the severity and frequency parameters (p less than 0.001), thus demonstrating the effectiveness of both treatments. No significant differences between groups were detected globally for the whole collective. For cough due to carcinomas (n = 14), however, a significantly better effect of butamirate on the frequency of cough (p = 0.026) was found which originated other significant differences in the global scores (p = 0.013) and in the physician's opinion (p = 0.026). Seven patients in both groups complained about side effects (mainly nausea and drowsiness).", "To show that prolonged survival can be observed after high-dose rate (HDR) endobronchial brachytherapy as the sole treatment for some selected patients presenting with an endobronchial malignant obstruction.\n Twenty-nine patients (group 1) who presented with an endoluminal localized tumor without metastatic extension were treated by HDR endobronchial brachytherapy and are compared with 22 subjects who presented with extraluminal dissemination and were palliatively treated (group 2). TREATMENT PROTOCOL: Treatment consisted of sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center of the applicator each, and repeated every 15 days, to a maximum of six exposures. Endoscopic response and survival are the main criteria of assessment.\n Follow-up bronchoscopies, performed 2 months after the end of the procedure, showed tumor regressions: macroscopic complete responses (CR) were observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with histologic CR in 18 and 2 patients, respectively. Median overall survival was not reached in group 1 after 23 months of follow-up; it was 5 months for group 2.\n These results confirm that HDR brachytherapy can be used as a monotherapy for carefully selected patients who have small tumors to all appearances limited to the bronchial lumen and bronchial wall without adjacent parenchymal extension or metastatic disease.", "Patients who present with symptomatic airway obstruction often have limited therapeutic options. Intraluminal irradiation has been used in an attempt to obtain sustained palliation. Patients treated with high dose-rate endobronchial irradiation have shown good to excellent palliation of symptoms, as well as a high rate of local control; however, these results have not always been devoid of complications. Some recent reports have shown a high incidence of morbidity, including an excessive incidence of fatal pulmonary hemorrhage. In this series, we report on 80 high dose-rate endobronchial treatments in 32 patients who were treated with remote afterloading endobronchial irradiation. All patients had endoscopic and histologic proof of tumor. Patients were divided into two groups. Group 1 consisted of 17 patients who were treated with endobronchial brachytherapy as a boost to primary external-beam irradiation. The remaining 15 patients comprised group 2 and were treated for endobronchial recurrence after prior irradiation with an external beam (main dose, 5,000 cGy). The endobronchial irradiation treatments were delivered using a high dose-rate remote afterloader. The standard dose per fraction was 500 cGy prescribed at a distance of 1 cm from the central axis of the catheter for a median of 3 fractions at weekly intervals. Treatment length averaged 5 cm; the median total dose was 1,500 cGy. The median follow-up for the entire group was 9.3 months, with a range of 6 to 24 months. Symptomatic improvement was attained in 15 of 15 patients presenting with hemoptysis, in 6 of 7 of those with cough, and in 10 of 10 who presented with dyspnea. In ten patients, follow-up endoscopy was performed, which revealed a pathologic complete response (by negative results on biopsies). At 6 months past the last brachytherapy, clinical and radiographic local control was obtained in 15/17 (88 percent) of the patients in group 1 and in 70 percent of the patients in group 2. All patients tolerated treatment well, without any acute or late complications, and there were no instances of fistula formation or fatal pulmonary hemorrhage. There was no association between the location of recurrence and complications. Fractionation, dose per fraction, and total combined dose appear to be important parameters in reducing complications.", "nan", "The study was designed to, (a) standardize endobronchial brachytherapy and, (b) to evaluate the relief of obstructive signs and symptoms.\n Patients with endobronchial carcinoma were treated on a protocol (n = 342) with remote afterloading brachytherapy. Group 1 patients were treated with medium dose rate and received 1000 cGy at 5 mm depth for three fractions (n = 47). Group 2 were treated with high dose rate, 1000 cGy to a 10 mm depth for three fractions (n = 144) and Group 3 received 750 cGy delivered to a 10 mm depth for three fractions (n = 151). Each group was divided into curative, palliative, and recurrent categories. Neodymium yttrium aluminum garnet photoresection was used in 24% of patients prior to brachytherapy.\n Evaluation consisted of symptom index scoring with weighted responses of hemoptysis 99%, obstructive pneumonia 99%, cough 85%, and dyspnea 86%. Obstruction improvement was 80% overall, curative 87%, palliative 84%, and recurrent 70% of mean pretreatment scores. Survival 10% alive, 88% expired, and 2% lost to follow-up. Cause of death was intrathoracic carcinoma 41%, metastatic carcinoma 38%, intercurrent disease 9%, and unknown cause 13%. Survival from diagnosis and first treatment was, respectively, for curative 10.8 and 9.5 months, palliative 14 and 5.6 months, and recurrent 25.6 and 6.2 months. Significant complications were fatal hemoptysis 7%, and radiation bronchitis and stenosis 11%.\n Endoluminal brachytherapy provides excellent palliation of the endobronchial portion of neoplastic disease.", "Nonproductive cough is a frequent and distressing symptom in patients with lung cancer, and it is not even relieved by palliative chemotherapy. A double-blind, randomized clinical trial regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg t.i.d.) were evaluated in comparison with dihydrocodeine drops (10 mg t.i.d.; 7 days). Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with either levodropropizine and dihydrocodeine, the antitussive effect and its time-profile being similar for both drugs. Also, according to the investigator's evaluation, both levodropropizine and dihydrocodeine produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine (n=6) and dihydrocodeine (n=4) group. However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favourable benefit/risk profile when compared to dihydrocodeine.", "We evaluated bronchoscopic tumor appearance and tumor location as determinants of response to high-dose rate brachytherapy (HDR-BT) in patients with symptomatic unresectable bronchogenic carcinoma previously treated with external-beam irradiation.\n Thirty patients with symptomatic endobronchial bronchogenic carcinoma who had previously completed external irradiation were divided into two groups based on whether the initial bronchoscopic appearance showed an endoluminal mass or submucosal infiltration/extrinsic compression. Furthermore, patients were also classified based on tumor location: central (trachea or mainstem bronchi) and peripheral (lobar or segmental bronchi). Patients underwent three treatments of 800 cGy intraluminal irradiation at 2-week intervals, with follow-up evaluation 4 weeks later. We evaluated response in tumor extent based on bronchoscopic and chest radiograph appearance, as well as symptoms with standardized scales.\n Fifteen of 24 patients who underwent follow-up bronchoscopy had reductions in the degree of endobronchial obstruction. Seven of 24 patients had radiographic improvement in the extent of atelectasis. Patients with both tumor appearances (endoluminal and submucosal/extrinsic compression) had significant improvements following HDR-BT with regard to hemoptysis. Patients with submucosal disease also had improvement in cough. Patients with peripheral tumors had better rates of response for hemoptysis and cough than did those with central tumors.\n HDR-BT may result in symptomatic improvement in patients with bronchogenic carcinoma, whether characterized endoscopically as endoluminal projection or submucosal infiltration/extrinsic compression. Peripheral tumors have better rates of response than central tumors, possibly on the basis of less extensive disease.", "C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough.", "A prospective controlled randomized trial was performed in order to assess the effectiveness and safety of photodynamic therapy versus laser resection in 31 patients with partial or complete tracheobronchial obstruction due to inoperable non-small cell lung cancer. Fourteen patients received dihaematoporphyrin ether and argon dye laser photoradiation, and 17 patients received Nd-YAG laser resection. Endoluminal obstruction of >75% was found in 77.4% of the patients. Among the symptoms, cough was more severe in the Nd-YAG group (p=0.02). Patients in both groups experienced symptomatic relief after treatment (p=0.003). Patients in the photodynamic therapy (PDT) group showed a significantly longer time until treatment failure (p=0.03) and longer median survival (p=0.007). Bronchitis and photosensitization (both in the PDT group) were the most common adverse effects. There was one death, probably related to treatment, in the PDT group. Photodynamic therapy and neodymium-yttrium aluminium garnet laser resection showed similar effectiveness and safety in the palliation of symptoms. The more prolonged survival in the photodynamic therapy group may have been due to differences in tumour stage between the groups. The degree of obstruction improved after treatment in both groups. In conclusion, photodynamic therapy is a valid method of palliation in partially or totally obstructing non-small cell lung carcinoma.", "To compare Nd: YAG laser resection with Nd: YAG laser plus brachytherapy and external beam radiotherapy (EBRT) in the palliation of malignant central airway obstruction symptoms due to lung cancer.\n In this prospective non-randomized study we evaluated the effects of Nd:YAG laser photoresection alone vs. Nd:YAG laser resection in combination with brachytherapy and EBRT on cough, dyspnoea, thoracic pain, haemoptysis, body weight loss, atelectasis, postobstructive pneumonia, endoscopic findings, disease-free period and survival rate in lung cancer patients. Only patients with Karnofsky index (KI) < or =50 were included. Sixty-four patients were divided into 2 groups: group I patients ( = 20) were treated only with Nd: YAG laser, and group II patients (n = 44) were treated with Nd: YAG laser followed by brachytherapy and EBRT.\n Group I patients showed statistically significant improvement in all investigated parameters but cough. Group II patients achieved significant improvement in all investigated parameters. Comparative statistical analysis between the 2 groups revealed statistically significant improvement in group II with regard to dyspnoea, haemoptysis, KI and atelectasis. No significant improvement in group II was seen when other investigated parameters were considered. Disease-free period and survival rate were significantly longer in group II (p< or =0.0005).\n The combination of interventional pulmonology procedures with standard modalities is the best option for the treatment of selected lung cancer patients.", "Endobronchial brachytherapy (EBBT) is an established modality for the palliation in advanced non-small cell lung cancer. We compared three different schedules using EBBT with or without external radiation (XRT) in this setting.\n Forty-five patients were randomized to three treatment arms. Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each. Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm. Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT. Symptomatic response rates, duration of symptom palliation, obstruction scores, quality of life outcomes and complications were assessed and compared.\n The overall symptomatic response rates were 91% for dyspnea, 84% for cough, 94% for hemoptysis and 83% for obstructive pneumonia. There was no significant difference between the arms. The median time to symptom relapse was 4-8 months for all symptoms and the median time to symptom progression was 6-11 months. The results were comparable between groups except for hemoptysis, where a shorter palliation was seen in Arm C that achieved statistical significance (P < 0.01). Quality of life showed significant improvement, with maximum benefit in Arm A. Complication rates were low. Only one patient died of fatal hemoptysis.\n EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer, either alone or in conjunction with XRT. The difference between the treatment arms were not statistically significant in most categories, but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied." ]

[ "18947426", "20832848", "16873437" ]

[ "Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study.", "Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants.", "A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age." ]

[ "Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.\n In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.\n Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.\n Current Controlled Trials ISRCTN16211826.", "Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult.\n To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life.\n Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group).\n A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group (P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants.\n Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.\n Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.", "Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora.\n To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis (AD) during the first six months of life in formula fed infants at high risk of atopy.\n Prospective, double-blind, randomised, placebo controlled trial; 259 infants at risk for atopy were enrolled. A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study. If bottle feeding was started, the infant was randomly assigned to one of two hydrolysed protein formula groups (0.8 g/100 ml prebiotics or maltodextrine as placebo). All infants were examined for clinical evidence of atopic dermatitis. In a subgroup of 98 infants, faecal flora was analysed.\n Ten infants (9.8%; 95 CI 5.4-17.1%) in the intervention group and 24 infants (23.1%; 95 CI 16.0-32.1%) in the control group developed AD. The severity of the dermatitis was not affected by diet. Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts.\n Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants. Although the mechanism of this effect requires further investigation, it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy." ]

[ "11779741" ]

[ "Randomized controlled study of an oral jaw-positioning appliance for the treatment of obstructive sleep apnea in children with malocclusion." ]

[ "To evaluate the clinical usefulness and tolerability of an oral jaw-positioning appliance in the treatment of obstructive sleep apnea syndrome in children, we studied 32 patients (mean age, 7.1 +/- 2.6 yr; 20 males) with symptoms of obstructive sleep apnea, malocclusion, and a baseline apnea index > 1 event/h. A group of 19 subjects was randomly assigned to a 6-mo trial of an oral appliance; the remainder acted as control subjects. At baseline and after the trial all patients underwent physical examination, a standard polysomnography, and orthodontic assessment. A modified version of the Brouillette questionnaire related to obstructive sleep apnea symptoms was administered to parents before and after the trial and a clinical score was calculated. Of the 32 subjects enrolled, 4 treated subjects and 5 control subjects were lost to follow-up. Polysomnography after the trial showed that treated subjects all had significantly lower apnea index (p < 0.001) and hypopnea index values (p < 0.001) than before the trial, whereas in untreated control subjects these values remained almost unchanged. Clinical assessment before and after treatment showed that in 7 of the 14 subjects (50%) the oral appliance had reduced (a fall of at least 2 points in the respiratory score) and in 7 had resolved the main respiratory symptoms, whereas untreated patients continued to have symptoms. In conclusion, treatment of obstructive sleep apnea syndrome with an oral appliance in children with malocclusion is effective and well tolerated." ]

[ "11999177", "12757433", "16944192" ]

[ "Real-time, evidence-based medicine instruction: a randomized controlled trial in a neonatal intensive care unit.", "Educational workshop improved information-seeking skills, knowledge, attitudes and the search outcome of hospital clinicians: a randomised controlled trial.", "Effectiveness and efficiency of a literature search strategy to answer questions on the etiology of occupational diseases: a controlled trial." ]

[ "The study assesses potential for improving residents' evidence-based medicine searching skills in MEDLINE through real-time librarian instruction.\n Ten residents on a rotation in a neonatal intensive care unit participated.\n Residents were randomized into an instruction and a non-instruction group. Residents generated questions from rounds and searched MEDLINE for answers. Data were collected through observation, search strategy analysis, and surveys. Librarians observed searches and collected data on questions, searching skills, search problems, and the test group's instruction topics. Participants performed standardized searches before, after, and six-months after intervention and were scored using a search strategy analysis tool (1 representing highest score and 5 representing lowest score). Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction.\n Post-intervention, the test group formulated better questions, used limits more effectively, and reported greater confidence in using MEDLINE. The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting. The test and control groups had the following average search scores respectively: 3.0 and 3.5 (pre-intervention), 3.3 and 3.4 (post-intervention), and 2.0 and 3.8 (six-month post-intervention).\n Data suggest that measurable learning outcomes were achieved. Residents receiving instruction improved and retained searching skills six-months after intervention.", "A double-blind randomised controlled trial was conducted on a group of Hong Kong hospital clinicians. The objective was to test if a three-hour educational workshop (with supervised hands-on practice) is more effective (than no training) to improve clinical question formulation, information-seeking skills, knowledge, attitudes, and search outcomes. The design was a post-test-only control group; recruitment by stratified randomization (by profession), blocked at 800. End-user training was more effective than no training in improving clinical question formulation, in raising awareness, knowledge, confidence and use of databases, but had made no impact on preference for secondary databases. It changed the attitude of clinicians to become more positive towards the use of electronic information services (EIS). Participants had higher search performance and outcomes (satisfaction with information obtained (NNT = 3), EIS satisfaction (NNT = 3) and success in problem solving (NNT = 4)). The workshop improved knowledge and skills in evidence-based searching, but this effect gradually eroded with time. Search logs confirmed that follow-up is required if effects are to be sustained. Longer effects on search behaviours appear to be positive. A randomised controlled trial is valuable in identifying cause-and-effect relations and to quantify the magnitude of the effects for management decision-making.", "To evaluate the effectiveness and efficiency of a search strategy to find evidence-based answers to questions related to the possible occupational etiology of diseases.\n A controlled trial of 70 occupational health physicians and 55 insurance physicians who were asked to answer one out of four 'occupational disease case-vignettes' following the steps of evidence-based medicine (EBM). The intervention group were given the search strategy as a tool.\n The intervention group scored significantly better than the control group in answering the main question of the case-vignette correctly (57% versus 37%) using more adequate search terms. The intervention group scored significantly better regarding satisfaction with the applied search strategy (28% very satisfied versus 8%). We found no differences in time spent in solving the case or in the intention of future practice of EBM.\n The introduction and application of specific search strategies can have a positive effect on the effectiveness of searching literature. Future initiatives for developing and testing specific search strategies in the field of occupational health should be encouraged." ]

[ "16135584", "16707509", "20801444", "11679505", "17610879", "21872244", "15121557", "16045523", "19442782", "17803715", "17803714", "21122848", "16307967", "16764872", "16120856", "15760312", "11763977", "16051242", "11332212", "20846257" ]

[ "A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion.", "Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial).", "A randomized controlled trial of 400-μg sublingual misoprostol versus manual vacuum aspiration for the treatment of incomplete abortion in two Egyptian hospitals.", "Incomplete miscarriage: a randomized controlled trial comparing oral with vaginal misoprostol for medical evacuation.", "Comparison of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion.", "Oral misoprostol for the management of incomplete abortion in Ecuador.", "Two regimens of misoprostol for treatment of incomplete abortion.", "A randomised double blind trial comparing misoprostol or placebo in the management of early miscarriage.", "Two routes of administration for misoprostol in the treatment of incomplete abortion: a randomized clinical trial.", "Is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care? Results from a randomised trial in Burkina Faso, West Africa.", "Misoprostol for treatment of incomplete abortion at the regional hospital level: results from Tanzania.", "Oral misoprostol as an alternative to surgical management for incomplete abortion in Ghana.", "A randomized controlled study comparing 600 versus 1,200 microg oral misoprostol for medical management of incomplete abortion.", "A randomized study comparing efficacy and patient satisfaction in medical or surgical treatment of miscarriage.", "A comparison of medical management with misoprostol and surgical management for early pregnancy failure.", "A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage.", "Randomized outpatient clinical trial of medical evacuation and surgical curettage in incomplete miscarriage.", "Medical vs. surgical evacuation of first-trimester spontaneous abortion.", "[Spontaneous abortion. Drug treatment versus surgery].", "Comparative study between oral and sublingual 600 µg misoprostol for the treatment of incomplete abortion." ]

[ "To compare the safety, efficacy, and acceptability of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion in a hospital setting in Kampala, Uganda.\n Three hundred seventeen women with clinically diagnosed incomplete first-trimester abortions were randomized to treatment with either manual vacuum aspiration or 600 mug misoprostol orally to complete their abortions. All women received antibiotics posttreatment and were followed up 1-2 weeks later.\n Regardless of treatment allocation, nearly all women in this study successfully completed their abortions with either oral misoprostol or manual vacuum aspiration (96.3% versus 91.5%, relative risk 1.05, 95% confidence interval 0.98-1.14). Complications were less frequent in those receiving misoprostol than those having manual vacuum aspiration (0.9% versus 9.8%, relative risk 0.1, 95% confidence interval 0.01-0.78). In the 6 hours after treatment, women using misoprostol reported heavier bleeding but lower levels of pain than those treated with manual vacuum aspiration. Rates of acceptability were similarly high among women in the 2 treatment groups, with 94.2% and 94.7% of women reporting that their treatment was satisfactory or very satisfactory in the misoprostol and manual vacuum aspiration groups, respectively.\n For treatment of first-trimester uncomplicated incomplete abortion, both manual vacuum aspiration and 600 microg oral misoprostol are safe, effective, and acceptable treatments. Based on availability of each method and the wishes of individual women, either option may be presented to women for the treatment of incomplete abortion.\n I.", "To ascertain whether a clinically important difference exists in the incidence of gynaecological infection between surgical management and expectant or medical management of miscarriage.\n Randomised controlled trial comparing medical and expectant management with surgical management of first trimester miscarriage.\n Early pregnancy assessment units of seven hospitals in the United Kingdom.\n Women of less than 13 weeks' gestation, with a diagnosis of early fetal demise or incomplete miscarriage.\n Expectant management (no specific intervention); medical management (vaginal dose of misoprostol preceded, for women with early fetal demise, by oral mifepristone 24-48 hours earlier); surgical management (surgical evacuation).\n Confirmed gynaecological infection at 14 days and eight weeks; need for unplanned admission or surgical intervention.\n 1200 women were recruited: 399 to expectant management, 398 to medical management, and 403 to surgical management. No differences were found in the incidence of confirmed infection within 14 days between the expectant group (3%) and the surgical group (3%) (risk difference 0.2%, 95% confidence interval - 2.2% to 2.7%) or between the medical group (2%) and the surgical group (0.7%, - 1.6% to 3.1%). Compared with the surgical group, the number of unplanned hospital admissions was significantly higher in both the expectant group (risk difference - 41%, - 47% to - 36%) and the medical group (- 10%, - 15% to - 6%). Similarly, when compared with the surgical group, the number of women who had an unplanned surgical curettage was significantly higher in the expectant group (risk difference - 39%, - 44% to - 34%) and the medical group (- 30%, - 35% to - 25%).\n The incidence of gynaecological infection after surgical, expectant, and medical management of first trimester miscarriage is low (2-3%), and no evidence exists of a difference by the method of management. However, significantly more unplanned admissions and unplanned surgical curettage occurred after expectant management and medical management than after surgical management. TRIAL REGISTRATION NATIONAL RESEARCH REGISTER: N0467011677/N0467073587.", "To compare the safety, efficacy, and acceptability of 400-μg sublingual misoprostol with that of manual vacuum aspiration (MVA) in 2 Egyptian hospitals.\n Participating women were randomized to either MVA or misoprostol treatment for incomplete abortion. The primary outcome, complete uterine evacuation, was determined 1 week later, as were adverse effects, change in hemoglobin, acceptability, and satisfaction.\n Complete uterine evacuation was achieved in 98.3% of women who received misoprostol and 99.7% who underwent MVA (relative risk [RR] 0.99; 95% confidence interval [CI], 0.97-1.00). A decrease in hemoglobin of 2g/dL or more was comparably rare in the 2 groups (0.3% misoprostol vs 0.9% MVA; RR 0.34 [95% CI, 0.04-3.21]). Mean change in hemoglobin was also clinically similar (-0.5 g/dL misoprostol vs -0.4 g/dL MVA; P<0.01). Heavy bleeding was rare (2.4% misoprostol vs 1.6% MVA; RR 1.55 [95% CI, 0.51-4.68]) following treatment. Nearly all women (96.8% misoprostol vs 98.3% MVA) were satisfied with their treatment but those who received misoprostol were significantly more likely to prefer that method in the future (81.9% vs 62.8%; RR 1.30 [95% CI, 1.19-1.43]).\n The high efficacy, safety, and acceptability of 400-μg sublingual misoprostol indicate that it is analogous to surgery as a first-line treatment for incomplete abortion. Misoprostol might improve post-abortion care when resources are limited and surgical treatment is unavailable.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "A prospective randomized controlled trial was conducted to compare the efficacy and side-effects of vaginal versus oral misoprostol in the medical management of incomplete miscarriage.\n Two hundred and one patients who miscarried consented to randomization using computer-generated randomization model prior to treatment. A total of 800 microg of misoprostol was given either vaginally or orally to the randomized subjects. A second dose was repeated 4 h later if the product of conception had not been passed.\n The incidence of complete uterine evacuation following vaginal and oral misoprostol was similar [(58/95) 61.1% versus (67/103) 64.4%]. There was a significantly decreased incidence of diarrhoea [(12/95) 13.6% versus (62/103) 65.3%, P < 0.01] with the use of vaginal misoprostol.\n Vaginal misoprostol was as effective as oral misoprostol in medical uterine evacuation in patients with incomplete miscarriage. There was also a reduction in the incidence of diarrhoea with the use of vaginal misoprostol.", "To compare the safety, efficacy, and acceptability of misoprostol versus manual vacuum aspiration (MVA) for treatment of incomplete abortion in Maputo, Mozambique.\n A total of 270 women with clinically diagnosed incomplete abortions of up to 12 weeks of gestation were randomized to either 600 mug oral misoprostol or MVA. Women were followed-up seven days later to evaluate whether the abortion was complete.\n Success was high for both MVA and misoprostol groups (100% vs 91%, P=0.002). Women in the MVA arm reported fewer side effects but higher pain scores. Women who received misoprostol were significantly more likely to be \"very satisfied\" with the treatment and willing to choose the method again.\n Although oral misoprostol was less effective than MVA in this study, it was more acceptable to women. Misoprostol is well-suited for use in low-resource settings, and should be promoted as an option for the treatment of incomplete abortion.", "To assess the feasibility of introducing misoprostol for the treatment of incomplete abortion in Quito, Ecuador.\n In a randomized prospective study conducted at a large tertiary-level maternity hospital and a private secondary-level clinic between November 2006 and November 2007, women with incomplete abortion were treated with either 600 μg of oral misoprostol (n=122) or manual vacuum aspiration (MVA) (n=120). All participants were requested to return for follow-up care on day 7 to determine the success of the treatment and to document their satisfaction with the method and the adverse effects experienced.\n Sixteen percent of women (39/242) did not return for their follow-up visit and their outcomes are unknown. Among those who did return, 94% (100/106) of women showed successful completion of abortion after treatment with misoprostol, as compared with 100% (97/97) of women treated with MVA. Most women described their adverse effects after treatment as tolerable (misoprostol, 95%; MVA, 91%). Nearly all women reported being satisfied with their treatment (196/203); there were no differences among the women's reports of satisfaction according to treatment received.\n An oral dose of 600 μg of misoprostol was found to be an acceptable and effective non-surgical option for treating incomplete abortion. Clinical trials.gov NCT00674232.\n Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "Misoprostol shows promise for treatment of incomplete abortion. We evaluated 2 simple misoprostol regimens to estimate whether they were effective in treating incomplete abortion.\n A total of 169 women was randomly assigned to either a single or double dose of 600 microg misoprostol. The women, who would have received a surgical evacuation of the uterus for incomplete abortion, were patients at 2 hospitals in Bangkok, Thailand. The 2 groups of women were compared for success of treatment (no need for surgical evacuation), side effects, and acceptability.\n Sixty-six percent of women in the single-dose group and 70% of women in the double-dose group had complete abortions with misoprostol. More than 90% of women in the single- and double-dose groups reported that the side effects were tolerable; frequency of side effects was similar between the 2 groups. Women found the treatment acceptable. Approximately 90% of women in both groups would recommend the treatment to a friend. Acceptability and efficacy were different at the 2 participating clinics.\n Misoprostol is an effective treatment for incomplete abortion. Simple regimens may be as effective as more complicated ones and a single dose of 600 microg should be further evaluated in larger trials.", "To study if misoprostol 400 microg, administered vaginally, increased the successful resolution of early miscarriage compared with placebo.\n Randomised, double blind placebo controlled study.\n Sahlgrenska University Hospital, Göteborg, Sweden.\n One hundred and twenty-six women seeking medical attention for early miscarriage.\n Women with a non-viable, first trimester miscarriage were randomised to vaginal administration of misoprostol 400 microg or placebo.\n Main outcome measure was the proportion of successful complete resolution of miscarriage. Secondary outcomes were incidence of infection, bleeding, gastrointestinal side effects, pain, use of analgesics and length of sick leave between groups.\n Sixty-four patients were randomised to misoprostol and 62 to placebo. Eighty-one percent in the misoprostol and 52% in the placebo group had a complete miscarriage within one week of the primary visit (RR 1.57; 95% CI 1.20-2.06). Patients in the misoprostol group reported more pain as assessed on a visual analogue scale (60.4 [31.0] vs 43.8 [37.1] mm; P < 0.007) and required analgesics more often (83%vs 61%, RR 1.35; 95% CI 1.08-1.70). There were no significant differences in the occurrence of gastrointestinal side effects, infection, reduction in haemoglobin or sick leave between the groups.\n Treatment with 400 mug misoprostol administered vaginally increased the success rate of resolvement of uncomplicated early miscarriages compared with placebo. However, women who received misoprostol experienced more pain and required more analgesics than those who did not.", "This study was conducted to compare the safety, effectiveness and acceptability of 400 mcg sublingual misoprostol and 600 mcg oral misoprostol for treatment of incomplete abortion.\n We used an open-label randomized controlled trial conducted from July 2005 to August 2006 in a large tertiary level maternity hospital in Antananarivo, Madagascar, and a large tertiary level hospital in Chisinau, Moldova. Three hundred consenting women seeking treatment for clinically diagnosed incomplete abortion with uterine size <or=12 weeks since last menstrual period were randomized to misoprostol either 600 mcg orally or 400 mcg sublingually. The primary outcome measure was the complete resolution of clinical signs and symptoms of incomplete abortion without need for surgical intervention. Women were seen for follow-up on Day 7 and, if necessary, on Day 14 to assess abortion status. The study was powered to detect a 7% difference in efficacy with a total of 142 women required in each arm.\n Efficacy rates were 94.6% and 94.5%, for the oral and sublingual routes, respectively (RR: 1.00, 95% CI=0.95-1.06, p=.98). At 1 week follow-up, more than 80% of women had completed abortions (77.8% oral and 84.8% sublingual, p=.12). Mean pain scores were 2.95 and 3.04, respectively, for the oral and sublingual groups. Side effects included abdominal pain, bleeding, headaches and dizziness/weakness with no differences reported between the two groups. Acceptability and satisfaction were high for both routes and women indicated a preference for medical versus surgical treatment if ever needed in the future.\n Both treatment regimens were very effective. Four hundred micrograms of sublingual misoprostol and 600 mcg oral misoprostol appear to have similar safety and effectiveness profiles when used for the treatment of incomplete abortion. A lower 400-mcg misoprostol dose may provide an alternative treatment option as well as have potential benefits in terms of cost.", "Previous research has demonstrated the effectiveness of misoprostol for treatment of incomplete abortion; however, few studies have systematically compared misoprostol's effectiveness with that of standard surgical care. This study documents the effectiveness of a single 600 micrograms dose of oral misoprostol versus manual vacuum aspiration (MVA) for treatment of incomplete abortion in a developing country setting.\n Open-label randomised controlled trial.\n Two university teaching hospitals in Burkina Faso, West Africa.\n Women of reproductive age presenting with incomplete abortion.\n From April 2004 through October 2004, 447 consenting women with incomplete abortion were randomised to either a single dose of 600 micrograms oral misoprostol or MVA for treatment of their condition.\n Completed abortion following initial treatment.\n Regardless of treatment assigned, nearly all participants had a complete uterine evacuation (misoprostol = 94.5%, MVA = 99.1%; relative risk [RR] = 0.95 [95% CI 0.92-0.99]). Acceptability and satisfaction ratings were similar and high for both misoprostol and MVA, with three out of four women indicating that the treatment's adverse effects were tolerable (misoprostol = 72.9%, MVA = 75.8%; RR = 0.96 [95% CI 0.86-1.07]). The majority of women were 'satisfied' or 'very satisfied' with the method they received (misoprostol = 96.8%, MVA = 97.7%; RR = 0.99 [95% CI 0.96-1.02]), expressed a desire to choose that method again (misoprostol = 94.5%, MVA = 86.6%; RR = 1.09 [95% CI 1.03-1.16]) and to recommend it to a friend (misoprostol = 94.5%, MVA = 85.2%; RR = 1.11 [95% CI 1.04-1.18]).\n Six hundred micrograms of oral misoprostol is as safe and acceptable as MVA for the treatment of incomplete abortion. Operations research is needed to ascertain the role of misoprostol within postabortion care programmes worldwide.", "To investigate the safety, efficacy, and acceptability of misoprostol versus manual vacuum aspiration (MVA) for treatment of incomplete abortion.\n A prospective open-label randomised trial.\n Kagera Regional Hospital, Bukoba, Tanzania.\n Three hundred women with a clinical diagnosis of incomplete abortion and a uterine size <12 weeks.\n A total of 150 women were randomised to either a single dose of 600 micrograms of oral misoprostol or MVA. If abortion was clinically complete at 7-day follow up, the woman was released from the study. If it was still incomplete, the woman was offered the choice of an additional 1-week follow up or immediate MVA. Cases still incomplete after a further week were offered MVA.\n Incidence of successful abortion (success defined as no secondary surgical intervention provided), incidence of adverse effects, patient satisfaction.\n Success was very high in both arms (misoprostol: 99%; MVA: 100%; difference not significant). Most adverse effects were higher in the misoprostol arm, although the mean pain score was higher in the MVA arm (3.0 versus 3.5; P < 0.001). More women were very satisfied with misoprostol (75%) than with MVA (55%, P = 0.001), and a higher proportion of women in the misoprostol arm said that they would recommend the treatment to a friend (95% versus 75%, P < 0.001).\n Misoprostol is as effective as MVA at treating incomplete abortion at uterine size of <12 weeks. The acceptability of misoprostol appears higher. Given the many practical advantages of misoprostol over MVA in low-resource settings, misoprostol should be more widely available for treatment of incomplete abortion in the developing world.", "To investigate whether 600-μg oral misoprostol is an effective alternative to manual vacuum aspiration (MVA) for the treatment of incomplete abortion.\n From June 16, 2004, to July 20, 2005, 230 women of reproductive age presenting with incomplete abortion were randomized in an open-label trial to either 600-μg oral misoprostol or MVA for the treatment of incomplete abortion.\n Regardless of the assigned method, more than 98% of participants experienced complete uterine evacuation following initial treatment. Efficacy, acceptability, and satisfaction ratings were similar and high for both methods.\n 600-μg oral misoprostol is a safe, effective, and acceptable alternative to MVA for the treatment of incomplete abortion.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "Although a number of studies have shown misoprostol's promise as a nonsurgical treatment for incomplete abortion, few have systematically examined treatment protocols. This study documents the effectiveness of 600 versus 1,200 microg oral misoprostol for this indication.\n From May 2002 to January 2003, 300 women with incomplete abortion were recruited at a large tertiary facility in Vietnam and randomized to either a single-dose (600 microg) or a repeated-dose (600 microg x 2) regimen of oral misoprostol for the treatment of their condition.\n Misoprostol effectively evacuated the uterus for nearly all women (94.6%; n=279), with most reporting bleeding for 4 days (+/-2.3) and pain/cramps lasting 1 day (+/-1.0). Women indicated that the side effects were tolerable (96%) and that their experience was satisfactory (95%).\n Oral misoprostol (600 or 1,200 microg) offers a safe, effective and acceptable treatment for incomplete abortion. Larger studies to assess the advantages and disadvantages of misoprostol as compared with standard surgical care are needed to assess its role in postabortion care programs worldwide.", "To compare the efficacy of the medical treatment to surgical uterine evacuation and patient satisfaction in each group.\n A randomized, controlled study.\n An outpatient clinic in the Department of Gynecology and Obstetrics in Oulu University Hospital, Oulu, Finland.\n Ninety-eight eligible women who had had miscarriages.\n Medical treatment of miscarriage (n = 49) with 200 mg of mifepristone and 0.8 mg of misoprostol 1-3 days after the event or surgical uterine evacuation (n = 49). Questionnaires to collect data of experienced pain and patient satisfaction.\n The complete abortion rate with the primary treatment (primary outcome) and the patient satisfaction (secondary outcome).\n The success rate was equal (100% in surgical and 90% in medical group). More infections were diagnosed in the surgical group. Surgically treated patients were more satisfied with the treatment (100% vs. 88%). Medical treatment was considered more painful and fewer patients (70% vs. 91%) would choose the medical method in the future.\n Medical treatment is an effective alternative to surgical treatment and increases the choice available to women. Surgical treatment is associated with more infections. More medically treated patients experienced pain and dissatisfaction.", "Misoprostol is increasingly used to treat women who have a failed pregnancy in the first trimester. We assessed the efficacy, safety, and acceptability of this treatment in a large, randomized trial.\n A total of 652 women with a first-trimester pregnancy failure (anembryonic gestation, embryonic or fetal death, or incomplete or inevitable spontaneous abortion) were randomly assigned to receive 800 microg of misoprostol vaginally or to undergo vacuum aspiration (standard of care) in a 3:1 ratio. The misoprostol group received treatment on day 1, a second dose on day 3 if expulsion was incomplete, and vacuum aspiration on day 8 if expulsion was still incomplete. Surgical treatment (for the misoprostol group) or repeated aspiration (for the vacuum-aspiration group) within 30 days after the initial treatment constituted treatment failure.\n Of the 491 women assigned to receive misoprostol, 71 percent had complete expulsion by day 3 and 84 percent by day 8 (95 percent confidence interval, 81 to 87 percent). Treatment failed in 16 percent of the misoprostol group and 3 percent of the surgical group (absolute difference, 12 percent; 95 percent confidence interval, 9 to 16 percent) by day 30. Hemorrhage or endometritis requiring hospitalization was rare (1 percent or less in each group), with no significant differences between the groups. In the misoprostol group, 78 percent of the women stated that they would use misoprostol again if the need arose and 83 percent stated that they would recommend it to others.\n Treatment of early pregnancy failure with 800 microg of misoprostol vaginally is a safe and acceptable approach, with a success rate of approximately 84 percent.\n Copyright 2005 Massachusetts Medical Society.", "Medical management and expectant care have been considered possible alternatives to surgical evacuation of the uterus for first trimester spontaneous miscarriage in recent years.\n To compare the effectiveness and safety of medical and expectant management with surgical management for first trimester incomplete or inevitable miscarriage.\n Forty women were recruited following diagnosis of incomplete or inevitable miscarriage, and randomised to surgical, medical or expectant care via an off-site, computerised enrollment system. The primary outcome was the effectiveness of medical (vaginal misoprostol) and expectant management relative to surgical evacuation, assessed at 10-14 days and 8 weeks post-recruitment. Infection, pain, bleeding, anxiety, depression, physical and emotional recovery were assessed also. Analysis was by intention-to-treat.\n Effectiveness at 8 weeks was lower for medical (80.0%) and expectant (78.6%) than for surgical management (100.0%). Two women in the medical group had confirmed infections. Bleeding lasted longer in the expectant group than in the surgical group. There were no significant differences in pain, physical recovery, anxiety or depression between the groups. 54.6%, 42.9% and 57.1% of the surgical, medical and expectant groups respectively would opt for the same treatment again.\n Expectant care appears to be sufficiently safe and effective to be offered as an option for women. Medical management might carry a higher risk of infection than surgical or expectant care.", "To compare the efficacy and safety of misoprostol in outpatient medical evacuation with surgical curettage in uncomplicated incomplete spontaneous miscarriage.\n Eighty women with a history of vaginal bleeding, and passage of some products of the conceptus were randomized into two groups. Forty patients in Group 1 received 200 microg misoprostol q.i.d. after the application of 200 microg intravaginal misoprostol for 5 days; 40 patients in Group 2 had a surgical curettage performed. All of the patients were re-evaluated after 10 days. The success rates, mean number of days of bleeding, mean decreases in hemoglobin levels, the complications and the rates of patient dissatisfaction in the two groups were compared.\n The success rate in the misoprostol-administered group was 95% [corrected]. Although the mean number of days of bleeding was significantly higher in the misoprostol-administered group, the mean decreases in hemoglobin values in the two groups were not significantly different. The patient dissatisfaction rate was 2.5% in the misoprostol group, compared to 35% in the control group. The difference between the two groups was significant.\n The use of misoprostol in the outpatient treatment of uncomplicated incomplete spontaneous miscarriage is safe and effective and can be an alternative to surgical evacuation and expectant management.", "To determine whether management of incomplete first-trimester abortion with vaginal misoprostol in an under-resourced setting is a viable treatment option.\n A total of 94 women were randomized to 600 microg of misoprostol intravaginally or to surgical curettage. The women receiving misoprostol were administered a second dose if the abortion was incomplete; and if still not complete after a week, evacuation of retained products of conception was performed. All women had a follow-up visit 2 weeks following complete abortion.\n The overall success rate of medical management was 91.5%, with 15 of 47 successful cases after 1 dose of misoprostol; 8.5% of the 47 women required evacuation of retained products of conception after 1 week because of treatment failure. The success rate in the surgical arm was 100%. Patients in the medical arm had a longer duration of bleeding and a greater need for analgesia. There were no differences in hemoglobin levels, white blood cell count, adverse effects, pain score, and satisfaction with treatment at the follow-up visit. However, more women who received the medical treatment would recommend it or choose it in the future.\n Medical management using 600 microg of misoprostol in 2 doses is effective to treat incomplete first-trimester abortions in an under-resourced setting when there is no evidence of uterine sepsis.", "Studies of conservative management of early miscarriage have questioned the need for post abortem curettage.\n A prospective, randomised study was carried out to clarify the effect of vaginal administration of a prostaglandin E1 analogue (gemeprost) versus surgical management (curettage) of miscarriages at up to twelve weeks of gestation. A questionnaire revealed discomfort as bleeding and pain.\n The study comprised 61 patients: group 1 (n: 27) with an endometrial thickness less than 10 mm managed by expectancy, and group 2 with an endometrial thickness greater than 10 mm; group 2 was randomised to group 2A (n: 17), given gemeprost, and group 2B (n: 17), underwent curettage. On entry the mean gestational ages were 51 and 67.5 days for groups 1 and 2, respectively; transvaginal ultrasonography revealed a mean endometrial thickness of 8 mm in group 1 and 19 mm in group 2. One week later this was reduced to 4 mm in group 1 and 5.7 mm in group 2. The duration of vaginal bleeding was similar in all groups, with a mean of 1 week (2-3 days of moderate/heavy bleeding and 6-10 of no bleeding or spotting). The discomfort experienced was similar in all groups (a mean of 36-48 hours of moderate/strong pain and 7-10 days of no or insignificant pain).\n Conservative treatment can substitute general anesthesia and curettage in the management of complete spontaneous abortions with fresh vaginal bleeding and an endometrial thickness of up to 10 mm. Vaginal administration of 1 mg gemeprost can substitute general anesthesia and curettage in the management of incomplete spontaneous abortions of up to 12 weeks of gestation and absence of a gestation sac.", "To evaluate and compare effectiveness, side effects and patient acceptability between oral and sublingual 600 µg misoprostol for the treatment of incomplete abortion.\n A randomized controlled trial was conducted. Pregnant women of less than 14 weeks gestation, diagnosed with incomplete abortion, were randomly assigned to receive 600 µg misoprostol orally or sublingually. The patients were evaluated at 48 h after drug administration for complete abortion.\n A total of 64 women were recruited to the study (32 in the oral group and 32 in the sublingual group). The complete abortion rate was not statistically different between oral and sublingual groups (87.5% versus 84.4%, P > 0.05). There was no statistical difference in side effects and satisfaction rate. Fever/chills were the most common side effects.\n Both sublingual and oral 600 µg misoprostol are useful for the management of incomplete abortion. Side effects and satisfaction rates are not different. Thus, these methods may be used as alternative treatments of incomplete abortion.\n © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology." ]

[ "10626340", "12659989", "11286304", "4970482", "3516053", "12418118", "3101636", "9781975", "4864732", "2199589", "2093381", "12515103", "8198938", "2947149", "7645522", "9404250" ]

[ "[Comparative efficacy of combined therapy with preductal and amino acid composition in elderly patients with coronary heart disease and class II-III angina].", "Treatment of stable angina with low dose diltiazem in combination with the metabolic agent trimetazidine.", "Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies.", "Trimetazidine in the treatment of angina pectoris.", "[Value of the combination of trimetazidine and a calcium inhibitor in the treatment of chronic coronary insufficiency. Double-blind controlled study versus placebo].", "[Decrease in the sensitivity to the anti-ischemic effect of propranolol and prospects for correcting it in patients with stable angina pectoris].", "[The effects of trimetazidine on ergometric parameters in exercise-induced angina. Controlled multicenter double blind versus placebo study].", "Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease.", "Trimetazidine in the treatment of angina pectoris.", "Trimetazidine and stable angina a double-blind trial.", "Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study.", "[Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers].", "Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group.", "[Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency. A double-blind versus placebo study].", "Combination therapy of trimetazidine with diltiazem in patients with coronary artery disease. Group of South of France Investigators.", "Combination treatment with trimetazidine and diltiazem in stable angina pectoris." ]

[ "A comparative analysis of effectiveness of combined therapy including trimetazidine (preductal) and composition of amino acids (glutamic acid, glycin and cystein) in elderly patients with coronary heart disease and angina of functional class II-III (FC II-III).\n 60 patients (47 females and 13 males, mean age 66.4 +/- 0.5 years) with IHD, angina FC II-III, postinfarction cardiosclerosis and circulatory failure stage I-IIA were randomized into 3 randomized groups. Control patients received conventional antianginal therapy with nitrates, beta-adrenoblockers, calcium antagonists, diuretics, ACI inhibitors, cardiac glycosides and aspirin. Patients of group 1 received conventional treatment + complex of amino acids in dose 100 mg 3 times a day sublingually. Group 2 patients received adjuvant preductal for 20 days in dose 20 mg 3 times a day per os. Assessment was made clinically, with echo-CG data, bimanual isometric loading and Holter 24-h ECG monitoring.\n All the three methods showed antianginal, hypotensive effects, brought higher tolerance to exercise and improvement of hemodynamics. The basic therapy produced the least effect.\n Metabolic therapy with amino acids and preductal combined with conventional methods brings more pronounced antianginal and hemodynamic effects than combined therapy alone.", "The risk/benefit of moderate to high doses of calcium antagonists in stable angina is uncertain. This study investigates the efficacy and acceptability of low dose diltiazem in combination with trimetazidine for the treatment of stable angina.\n In a 28-day, randomized, double blind study, treatment with 90 mg diltiazem in combination with 60 mg trimetazidine or placebo per day was compared in 50 patients with stable angina. The primary outcomes were time to 1-mm ST segment depression and the Duke treadmill score.\n Of the 25 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was, in time to 1-mm ST segment depression, 13 (52) versus 5 (20), P<0.05; in the Duke treadmill score, 18 (72) versus 8 (32), P<0.01; and in angina 17 (68) versus 3 (12), P<0.01. Compared to placebo there was an improvement with trimetazidine in mean exercise time to 1-mm ST segment depression of 128 s (95% confidence interval 45.0-208.5; P<0.01); in the mean Duke treadmill score of 57.4% (95% confidence interval 9.9-100; P<0.02); and in mean anginal attacks of 5.1 per week (95% confidence interval, 3.1-7.3, P<0.01).\n The combination of low dose diltiazem with trimetazidine is effective with few side-effects in the symptomatic control of patients with stable angina.", "Several clinical studies have compared the anti-ischaemic properties of trimetazidine used as monotherapy with those of standard anti-anginal therapy. In the treatment of uncontrolled angina pectoris, the addition of a metabolic agent such as trimetazidine to existing therapy with a haemodynamic agent would appear to confer advantages over the addition of a second haemodynamic agent. Here we report the results of three studies conducted in Poland, the Czech Republic and Hungary that provide additional evidence for the beneficial effects of combining trimetazidine with a conventional haemodynamic agent such as beta-blockers, long-acting nitrate or calcium channel blockers. This combination provided significant benefits in terms of improved exercise capacity and decreased number of angina attacks along with a good tolerability profile.", "nan", "nan", "To study incidence of low sensitivity to an antiischemic effect of propranolol and feasibility of its correction with a metabolic drug--trimetazidine.\n Paired treadmill and bicycle exercise tests were made until depression of segment ST > 1 mm and a typical angina episode. The trial included 147 men with ischemic heart disease, stable angina pectoris (functional class II-III). The antiischemic effect of propranolol single doses 40 or 80 mg were assessed in 117 patients. Single doses of propranolol 40 mg, trimetazidine 20 mg and their combination were examined for an antiischemic effect in 30 patients. The absence of the above effect of propranolol was stated in 20 patients who participated in a double blind, randomised, placebo-controlled study with conduction of 2-week courses of regular administration of propranolol in a dose 120 mg/day, trimetazidine 60 mg/day and their combination. Echo-CG was made initially and in the end of each course.\n Propranolol's antiischemic effect of a single dose 40 mg was not found in 45.3% patients, 40-80 mg--in 21%. Among 20 patients without effect of the single propranolol dose, an increment of the threshold load made up 20.7 +/- 15.7 s, after intake of trimetazidine 16.3 +/- 18.6 s. The combination of these drugs significantly increases the increment of the threshold load duration to 90.8 +/- 80.4 s. The same picture was observed in the course treatment. The above increment in the course administration of propranolol was 46.3 +/- 15.3 s, of trimetazidine 22.8 +/- 20.2 s, of their combination 122.7 +/- 21.8 s (p = 0.02). In the absence of propranolol effect, echo-CG registered deterioration of disorder of left ventricular diastolic function. 10 patients with effect of the single propranolol dose this deterioration was not observed in combined use of propranolol and trimetazidine.\n The antiischemic effect of propranolol in a single dose 40 mg was not recorded in about half of the examined anginal patients. Combined use of propranolol and trimetazidine in cases with no propranolol effect provides a synergetic effect both in single and course administration.", "The antianginal effect of trimetazidine was assessed by a controlled multicentre double-blind versus placebo trial. The study included 32 males, average age 59.5 years, with stable angina of effort. The stability of angina was determined by two exercise stress tests performed at the beginning and at the end of a 15 day pre-selection period under placebo. The patients included in the trial were given 3 tablets a day of either trimetazidine (20 mg per tablet) or of placebo for one month. At the end of the treatment period the patients underwent a third exercise stress test. Comparing the results of exercise testing before and after treatment by a Mann and Whitney test, a statistically significant improvement with trimetazidine was demonstrated with respect to placebo for three parameters: total work increased from 4200 +/- 372 to 5620 +/- 387 Kpm in the trimetazidine group compared to 4191 +/- 399 to 4564 +/- 431 Kpm for placebo (p = 0.012); the duration of exercise increased from 10.2 +/- 0.5 to 12.1 +/- 0.5 minutes with trimetazidine compared to 10.2 +/- 0.5 to 10.7 +/- 0.5 with placebo (p = 0.016); the period to 1 mm ST depression increased from 8.3 +/- 0.6 to 9.8 +/- 0.5 minutes with trimetazidine compared to 8.4 +/- 0.5 to 9.0 +/- 0.7 minutes with placebo (p = 0.034). These results show that signs of ischaemia are delayed by trimetazidine. There were no significant changes in peripheral haemodynamics at rest or on effort. The antianginal action of trimetazidine seems therefore to be unrelated to a chronotropic or vasomotor effect and could be related to a mechanism of cellular regulation.", "We studied 15 patients with chronic coronary artery disease (13 men aged 62 +/- 8 years) undergoing dobutamine (5 to 40 microg/kg/min) echocardiography at the end of two 15-day treatment periods with placebo and trimetazidine (20 mg 3 times daily) given in random order, according to a double-blind, crossover design. Results show that trimetazidine improves resting left ventricular function and reduces the severity of dobutamine-induced ischemic myocardial dysfunction.", "nan", "The effect of trimetazidine was evaluated in patients with stable angina by adding it to the other antianginal regimen in a double blind crossover design each of 8 week's duration. The method of evaluation made use of symptom recall, daily dairy of the intake of sublingual nitrates or of anginal discomfort and in some, symptom limited treadmill exercise stress test (EST). Thirty-six patients completed the trial. Symptom-wise, 16 patients could not differentiate the effect of the true tablet from the placebo. Eight had less and 12 had more angina while on the drug. Of the 17 evaluable EST, 9 showed no change in the degree of ischemic changes while 4 performed with less and 4 with more ischemia while on the drug. Symptom-wise and taking into account the pre and post trial periods, a placebo effect was not found to be dominant. It is concluded that trimetazidine does not improve angina among those already being treated with conventional doses of nitrates, beta and calcium blockers.", "Trimetazidine has been shown to have an antianginal effect, increasing exercise capability without producing any significant change of heart rate or systolic blood pressure. The aim of this study was to compare trimetazidine efficiency to that of another classical antianginal drug. A double-blind crossover trimetazidine versus nifedipine trial was carried out in 39 male patients, mean age 58 years, with effort angina for 5 years on average, and a mean number of weekly attacks of 2.4. Thirteen patients had previous myocardial infarction. Nineteen patients received nifedipine (40 mg per day) then trimetazidine (60 mg per day), and 20 patients received the drugs in the opposite order. Each therapeutic period of 6 weeks was preceded by 1 week of washout with placebo. Drug efficacy was assessed by a bicycle exercise tolerance test, performed at the beginning and at the end of each therapeutic period, and by clinical symptoms observed with placebo or with treatment. The statistical analysis was performed according to a crossover design, with repeated measurements. The decrease of the number of weekly attacks was not significantly different with trimetazidine and nifedipine. Results on the exercise test showed no significant differences for maximum workload, the duration of exercise, ST-segment depression at peak exercise, and the time to 1-mm ST-segment depression. Heart rate and systolic blood pressure were not significantly different at rest and at peak exercise. However, the change in the rate-pressure product at the same workload differed significantly between the drugs: It decreased with nifedipine and remained unchanged with trimetazidine, indicating the difference to be in the mode of action of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)", "The extended use of interventional surgery of revascularisation has modified the prognosis and the evolution of ischaemic heart diseases. However, both coronary artery bypass graft and percutaneous transluminal coronary angioplasty failed to make the symptomatic or subclinical ischaemic manifestations of chronic coronary insufficiency disappear. The interest of using betablockers as a first-line therapy was widely demonstrated. However, their combination with another efficient molecule is often necessary. The aim of this trial has been to appreciate the efficiency of the association of a betablocker with either trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients retaining a positive effort test despite 100 mg of atenolol, received in addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide mononitrate (92 cases) for a two-month period and are then re-evaluated at the end of this period. The ischaemic threshold is delayed in a significant way in both groups (p < 0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%). Twenty-three percent of the exercise tests under trimetzidine and 19% under isosorbide mononitrate become negative after two months of the therapeutic combination. The clinical improvement is even clearer with the disappearance of the angina crisis during the week before the second exercise test in 63% of the cases under trimetazidine and 54% of the cases under isosorbide mononitrate, among the patients who had kept it under atenolol at the inclusion. In conclusion, the combination of a second efficient molecule, trimetazidine or isosorbide mononitrate, brings a functional and objective improvement to patients with insufficient chronic coronary disease not totally controlled using a betablocker, even with high dosage. One should notice two important advantages in favour of the trimetazidine: one is practical due to a better tolerance (lack of cephalalgia), the other is conceptual (use of the complementary metabolic approach of cellular oxygenation rather than the haemodynamic approach of nitrate compounds which are already in concurrency with all other anti-ischaemic molecules).", "1. Trimetazidine has a direct anti-ischaemic effect on the myocardium without altering the rate x pressure product or coronary blood flow. 2. The effects of trimetazidine (20 mg three times daily) were compared with those of propranolol (40 mg three times daily) in a double-blind parallel group multicentre study in 149 men with stable angina. 3. Reproducibility of exercise performance was verified during a 3 week run-in placebo washout period. All patients had > 1 mm ST-depression on exercise test. 4. After 3 months, similar anti-anginal efficacy was observed between the trimetazidine (n = 71) and propranolol (n = 78) groups. No significant differences were observed between trimetazidine and propranolol as regards anginal attack rate per week (mean difference P-TMZ: 2; 95% CI: -4.4, 0.5) and exercise duration (mean difference P-TMZ: 0 s; 95% CI: -33, 34) or time to 1 mm ST segment depression (mean difference P-TMZ: 13 s; 95% CI: -24, 51). Heart rate and rate x pressure product at rest and at peak exercise remained unchanged in the trimetazidine group but significantly decreased with propranolol (P < 0.001 in all cases). With both drugs there was a trend to decreased ischaemic episodes in the 46% patients who experienced ambulatory ischaemia on Holter monitoring. Six patients stopped trimetazidine and 12 propranolol. Of these, five in each group were withdrawn because of deterioration in cardiovascular status. 5. The results suggest that trimetazidine and propranolol at the doses studied have similar efficacy in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)", "The antianginal activity of trimetazidine (Vastarel 20 mg) was evaluated in a double blind study versus placebo. The 54 subjects of the survey were males, of mean age 55.2 +/- 1.4 years in the trimetazidine group and 55.5 +/- 1.8 years in the placebo group, suffering from stable angina. The stability of angina was tested by two exercise tests carried out at the beginning and at the end of a two-week preselection period under placebo. Three tablets daily of either trimetazidine or placebo were given at random for two weeks. At the end of that time, a third exercise test was carried out. The clinical results showed a significant reduction (P less than 0.001) in the number of weekly attacks from 8.1 +/- 0.3 to 2.9 +/- 0.5 under trimetazidine and from 7.6 +/- 0.2 to 4.9 +/- 0.5 under placebo. Moreover, nitroglycerin consumption over a week decreased from 9.1 +/- 0.6 to 3.1 +/- 0.5 tablets under trimetazidine and from 7.9 +/- 0.3 to 5.4 +/- 0.6 tablets under placebo. The difference was significant (P less than 0.001). The global evaluation of the exercise tests showed a significant difference in favor of trimetazidine: 19 patients out of 27 improved under trimetazidine, as compared to 11 out of 27 under placebo. The total workload-capacity after treatment was increased by 62.1% under trimetazidine, and by 24.7% under placebo (P = 0.007). The rate-pressure product diminished by 12% with trimetazidine and by 4% with the placebo. Nevertheless, the interaction was not significant (P = 0.079). This study made it possible to evaluate the significant reduction of stress attacks frequency and nitroglycerin consumption under trimetazidine versus placebo. This clinical improvement was assessed by ergometric parameters.", "The efficacy of trimetazidine, an antianginal agent with a direct effect on ischemic myocardium, has been tested alone or in combination with beta blockers or nifedipine. The combination with diltiazem, a widely used calcium antagonist, has not been studied. The aim of this study was to evaluate the potential benefit of oral trimetazidine (20 mg 3 times daily) in combination with oral diltiazem (60 mg three times daily). This was a multicenter, placebo-controlled study with a follow-up period of 6 months. Patients with stable angina and a positive exercise electrocardiogram before and after 15 days of diltiazem therapy were included. The 67 patients were randomized to diltiazem plus placebo (group I, 35 patients) and diltiazem plus trimetazidine (group II, 32 patients). Follow-up included a bicycle ergometer maximal exercise test and a physical examination at inclusion and at 3 and 6 months. The 2 groups were similar in terms of ergometric parameters, except for the ischemic threshold, defined as the time to 1-mm ST-segment depression. The latter was shorter in group II. Comparison of exercise tests performed at inclusion and after 6 months of therapy in both groups showed that the ischemic threshold was significantly prolonged (2 minutes 41 seconds; p < 0.001) in group II. This was not the case for group I, which showed a 41-second prolongation only (difference not significant). The work (kPM) produced at 1-mm ST-segment depression was also significantly increased in group II (1,445.9 kPM; p < 0.001) compared with group I (563.7 kPM; p = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina.\n Double blind, randomised, placebo controlled trial of four weeks duration.\n Outpatient department of two Indian hospitals.\n 64 male patients with stable angina, uncontrolled on diltiazem alone.\n Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily.\n Change in exercise time to 1 mm ST segment depression.\n 33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/ week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05).\n Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects." ]

[ "6349363" ]

[ "Pyelonephritis in pregnancy: a prospective randomized trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance." ]

[ "It has been advocated that if a patient develops acute pyelonephritis during pregnancy, she should receive suppressive therapy for the remainder of the gestation to prevent a recurrence of the disease. We have prospectively evaluated 200 patients following an acute episode of pyelonephritis during pregnancy. All patients were followed in a special clinic. Half the patients received nitrofurantoin as suppressive therapy. Recurrent pyelonephritis occurred in 7% of the patients receiving suppressive therapy versus 8% of those patients receiving close surveillance in the clinic. The results cast doubt upon the need for suppressive therapy and instead dramatized the beneficial effects of close surveillance with cultures. The data also suggest, at least in a high-risk population, that patients with gram-negative bacilluria of less than 10(5) colonies/ml may have a substantial risk of developing symptomatic recurrences. Prompt treatment of even low levels of gram-negative bacilluria should be considered in patients at risk for recurrent disease." ]

[ "17264106", "12154263", "17804936", "11022928", "16102151", "19479528", "14523701" ]

[ "Stress in caregivers of aphasic stroke patients: a randomized controlled trial.", "Telephone intervention with family caregivers of stroke survivors after rehabilitation.", "[The effects of a support group intervention on the burden of primary family caregivers of stroke patients].", "Family support for stroke: a randomised controlled trial.", "The impact of a nurse-led support and education programme for spouses of stroke patients: a randomized controlled trial.", "The effect of a Web-based stroke intervention on carers' well-being and survivors' use of healthcare services.", "Telephone group intervention for older stroke caregivers." ]

[ "Communication difficulties due to aphasia following stroke are particularly stressful to caregivers.\n To examine the impact of a psychoeducation programme on caregivers' burden and stress and communication between the caregiver and aphasic stroke patient.\n Randomized wait-list controlled trial with immediate or three-month delayed treatment.\n Three public hospital rehabilitation services in Sydney, Australia.\n Thirty-nine caregivers of aphasic stroke patients, up to 12 months post stroke: 19 given immediate treatment and 20 in a delayed treatment control group.\n Four-session weekly caregiver programme that included elements of education, support and communication skills conducted by a speech pathologist, social worker and clinical psychologist.\n The General Health Questionnaire (GHQ) was used to measure caregiver stress, the Relatives' Stress Scale was used to measure caregiver burden and a communication questionnaire was designed specifically for this project.\n Thirty-one caregivers completed the study. Caregivers in the immediate treatment group had significant reductions in GHQ measured stress (GHQ mean (SD) at baseline= 6.26 (5.67), GHQ post treatment 3.21 (SD 4.20), P = 0.006). There was no improvement in wait-listed caregivers. Improvement was not maintained at three-month follow-up. There were no significant effects of the programme on communication skills or on caregiver burden.\n Stroke caregiver support, education and training programmes have short-term effects on caregiver stress levels but are likely to require ongoing involvement to maintain their effect.", "Social problem-solving therapy shows promise as an intervention to improve the well-being of family caregivers. There is some evidence that training in problem solving may be effectively delivered by telephone. The purpose of this study was to quantify the impact of social problem-solving telephone partnerships on primary family caregiver outcomes after stroke survivors are discharged home from a rehabilitation facility.\n Using a randomized 3-group repeated-measures experimental design, 74 stroke survivors with an admitting diagnosis of ischemic stroke and their primary family caregivers were entered into the study. The intervention consisted of an initial 3-hour home visit between a trained nurse and the family caregiver within 1 week after discharge to begin problem-solving skill training. This initial session was followed by weekly (the first month) and biweekly (the second and third month) telephone contacts.\n Compared with the sham intervention and control groups, family caregivers who participated in the social problem-solving telephone partnership intervention group had better problem-solving skills; greater caregiver preparedness; less depression; and significant improvement in measures of vitality, social functioning, mental health, and role limitations related to emotional problems. There were no significant differences among the groups in caregiver burden. Satisfaction with healthcare services decreased over time in the control group while remaining comparable in the intervention and sham intervention groups.\n These results indicate that problem-solving training may be useful for family caregivers of stroke survivors after discharge from rehabilitative facilities.", "The purpose of this study was to develop and evaluate the effects of a support group intervention on the burden of primary family caregivers of stroke patients.\n A nonequivalent control group pretest-posttest design was used. The subjects were 36 primary family caregivers of stroke patients [experimental(N=18) and control(N=18) groups] in a neurosurgery ward of a university hospital. The experimental group members participated in six sessions of a support group intervention for two weeks and the degree of their caregiving burden was evaluated. Data was analyzed by Chi-square tests, t-tests, and paired t-tests using SPSS 10.0.\n The experimental group had a significantly lower total burden score (t=2.061, p= .047)and sub-scales of emotional(t=-3.319, p= .002), time-dependent(t=-2.045, p= .049) and developmental(t=-2.656, p= .012) burden scores than the control group, while no significant differences were found in physical, social or financial burden scores between the two groups. Within the experimental group, there was a significant decrease in physical(t=2.507, p= .023), emotional(t=4.754, p= .000), social(t=2.932, p= .009), time- dependent(t=5.015, p= .000) and developmental(t=7.541, p= .000) burden scores but not the financial burden score.\n The results suggest that a support group intervention can be utilized as an effective nursing program to reduce the burden of primary family caregivers of stroke patients.", "Attention is currently focused on family care of stroke survivors, but the effectiveness of support services is unclear. We did a single-blind, randomised, controlled trial to assess the impact of family support on stroke patients and their carers.\n Patients with acute stroke admitted to hospitals in Oxford, UK, were assigned family support or normal care within 6 weeks of stroke. After 6 months, we assessed, for carers, knowledge about stroke, Frenchay activities index, general health questionnaire-28 scores, caregiver strain index, Dartmouth co-op charts, short form 36 (SF-36), and satisfaction scores, and, for patients, knowledge about stroke and use of services, Barthel index, Rivermead mobility index, Frenchay activities index, London handicap scale, hospital anxiety and depression scales, Dartmouth co-op charts, and satisfaction.\n 323 patients and 267 carers were followed up. Carers in the intervention group had significantly better Frenchay activities indices (p=0.03), SF-36 scores (energy p=0.02, mental health p=0.004, pain p=0.03, physical function p=0.025, and general health perception p=0.02), quality of life on the Dartmouth co-op chart (p=0.01), and satisfaction with understanding of stroke (82 vs 71%, p=0.04) than those in the control group. Patients' knowledge about stroke, disability, handicap, quality of life, and satisfaction with services and understanding of stroke did not differ between groups. Fewer patients in the intervention group than in the control group saw a physiotherapist after discharge (44 vs 56%, p=0.04), but use of other services was similar.\n Family support significantly increased social activities and improved quality of life for carers, with no significant effects on patients.", "The aim of the present study was to determine the impact of a nurse-led support and education programme for improving the spouses' perceived general quality of life, life situation, general well-being and health state.\n Stroke is a disease with great consequences for the patients and their families. The spouses often feel obligated to care for the patient, providing psychological and physical support and having to cope with the patient's physical and cognitive impairments. This might lead to increased problems, as family members struggle to adapt to their new roles and responsibilities.\n Longitudinal, randomized controlled trial. One hundred spouses were randomly assigned to intervention or control groups, 50 in each group. The intervention group participated in a support and education programme, six times during six months, led by stroke specialist nurses. Both groups were followed for 12 months.\n No significant differences were found, between intervention and control groups, over time. In the sub analyses, we found that the group attending 5-6 times had a significant decrease in negative well-being and increased quality of life over time, while the group attending fewer times had a significant decrease in positive well-being and health state, similar to the control group, which also had a significant decrease in negative and general well-being.\n A support and education programme might have a positive effect on spouses' well-being, on condition that they attend at least five times.\n To facilitate the spouses' role as informal caregivers to the stroke patients, further development of the support and education programme used in the present study is needed, including empowerment approach and implementation of coping strategies.", "We hypothesised that carers of stroke survivors who participate in the Web-based intervention, Caring approximately Web, would have higher well-being than non-Web users. We also postulated that those survivors whose carers participated in Caring approximately Web would use fewer healthcare services.\n A randomised, two-group, repeated measures design was used. Subjects were recruited from four rehabilitation centres from which first-time stroke survivors were discharged to home in two Midwestern states. Of 144 carers screened, 103 carers of these survivors who were novice Internet users were assigned to a Web or non-Web user group. Seventy-three subjects completed the study.\n Caring approximately Web was a Web-based intervention of education and support provided to the Web user group for 1 year. A bi-monthly telephone survey collected data on all carers well-being (perceived depression, life satisfaction) and survivors healthcare service use (self-reported provider and emergency department visits, hospital re-admissions, nursing home placement).\n No statistical differences were found between the groups in carers well-being or in the number of provider visits for survivors. There were significant differences in emergency department visits (p = 0.001) and hospital re-admissions (p = 0.0005) related to the health of survivors.\n This Web-based intervention helped new carers make informed decisions about healthcare needs of stroke survivors, thus reducing service use.", "This study evaluated the effectiveness of telephone groups for older, spousal caregivers of stroke survivors.\n The 88 caregivers were mostly white females who were 70 years old on average and who had been providing care for an average of 3 years. Participants were randomized to treatment or control conditions, followed for 6 months, and assessed for depression, burden, loneliness, stress, and competence. Treatment participants engaged in an eight-session psychoeducational telephone group.\n Treatment participants showed decreased stress over time but were not significantly different from control participants in the amount of change in stress. Control participants showed a significant increase in burden during the study; treatment participants showed a significant increase in competence." ]

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[ "A randomised comparison and economic evaluation of laparoscopic-assisted hysterectomy and abdominal hysterectomy.", "Abdominal hysterectomy should not be considered as a primary method for uterine removal. A prospective randomised study of 100 patients referred to hysterectomy.", "Total laparoscopic hysterectomy versus total abdominal hysterectomy: an assessment of the learning curve in a prospective randomized study.", "The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy.", "Abdominal vs vaginal hysterectomy: a comparative study of the postoperative quality of life and satisfaction.", "A randomised prospective study of laparoscopic vaginal hysterectomy versus abdominal hysterectomy each with bilateral salpingo-oophorectomy.", "Metabolic and inflammatory responses after laparoscopic and abdominal hysterectomy.", "A randomized study of total abdominal, vaginal and laparoscopic hysterectomy.", "Identifying the indications for laparoscopically assisted vaginal hysterectomy: a prospective, randomised comparison with abdominal hysterectomy in patients with symptomatic uterine fibroids.", "Comparative study of vaginal, laparoscopically assisted vaginal and abdominal hysterectomies for uterine myoma larger than 6 cm in diameter or uterus weighing at least 450 g: a prospective randomized study.", "[Clinical comparison of laparoscopy-assisted vaginal hysterectomy (LAVH) and total laparoscopy hysterectomy (TLH) in women with benign disease of uterus--a prospective randomized study].", "Clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy: a randomized controlled study.", "Randomized, prospective, double-blind comparison of abdominal and vaginal hysterectomy in women without uterovaginal prolapse.", "Three methods for hysterectomy: a randomised, prospective study of short term outcome.", "Value of laparoscopic assistance for vaginal hysterectomy with prophylactic bilateral oophorectomy.", "Psychological wellbeing after laparoscopic and abdominal hysterectomy--a randomised controlled multicentre study.", "Pain and pulmonary function following laparoscopic and abdominal hysterectomy: a randomized study.", "Comparison of total laparoscopic hysterectomy and laparoscopically assisted vaginal hysterectomy.", "[Comparison of laparoscopically assisted vaginal hysterectomy with abdominal hysterectomy. Technique and results].", "Abdominal or vaginal hysterectomy for enlarged uteri: a randomized clinical trial.", "A randomised prospective trial comparing laparoscopic and abdominal hysterectomy.", "Prospective randomized comparison of laparoscopic-assisted vaginal hysterectomy (LAVH) with abdominal hysterectomy (AH) for the treatment of the uterus weighing >200 g.", "A multicenter randomized comparison of laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates.", "Total laparoscopic hysterectomy compared with abdominal hysterectomy in the presence of a large uterus.", "Quality of life and surgical outcome after total laparoscopic hysterectomy versus total abdominal hysterectomy for benign disease: a randomized, controlled trial.", "Is laparoscopic hysterectomy a waste of time?", "[Total laparoscopic hysterectomy versus vaginal hysterectomy: a prospective randomized trial].", "Recovery from vaginal hysterectomy compared with laparoscopy-assisted vaginal hysterectomy: a prospective, randomized, multicenter study.", "Laparoscopic-assisted vaginal hysterectomy versus minilaparotomy hysterectomy: a prospective, randomized, multicenter study.", "Vaginal hysterectomy for enlarged uteri, with or without laparoscopic assistance: randomized study.", "Laparoscopically assisted vaginal hysterectomy versus total abdominal hysterectomy: a prospective, randomized, multicenter study.", "Laparoscopically assisted vaginal hysterectomy versus total abdominal hysterectomy: a study of 100 cases on light-endorsed transvaginal section." ]

[ "To determine the safety, cost effectiveness and effect on quality of life of laparoscopic-assisted vaginal hysterectomy (LAVH) compared with total abdominal hysterectomy (TAH) in the management of benign gynaecological disease.\n Randomised controlled trial and economic evaluation.\n Three hospitals in the West of Scotland.\n Two hundred women scheduled for an abdominal hysterectomy for benign gynaecological disease.\n Conversion rate of LAVH to TAH, complication rates, NHS resource use and costs, quality of life using EuroQol 5 D visual analogue scale, and achievement of milestones.\n The overall incidence of operative complications was 14% in the TAH group and 8% in the LAVH group, with an 8% conversion rate. Length of operation was significantly greater in the women having LAVH at 81 +/- 30 min vs 47 +/- 16 min (P < 0.001). There was no difference in analgesic requirements between the groups although there was a significantly shorter hospital stay for those having LAVH. The rate of post-surgery recovery, satisfaction with operation and quality of life at four weeks post-operative were similar in the two groups of women. LAVH was significantly more expensive than TAH and remained more expensive for all but the most extreme scenario.\n This study demonstrates that despite the decreased length of hospital stay, LAVH is more expensive than TAH. In addition, recovery following operation and patient satisfaction were not affected by the route chosen. It is unlikely that LAVH represents an efficient use of NHS resources.", "The present study is a prospective randomized comparison of laparoscopically assisted vaginal hysterectomy (LH) with total abdominal hysterectomy (TAH).\n 100 patients referred for uterine removal were included in the study, 46 undergoing LH and 54 TAH, at two teaching hospitals in Norway.\n In the LH group, the duration of surgery was longer while duration of hospitalization and time from operation to return to normal activity were shorter as compared to the TAH group. Postoperative pain, assessed by the need for analgesics, was less in the LH group. All these differences were statistically significant. There were two ureteral lesions in the LH group, and one center withdrew early from the study for this reason.\n In expert hands, LH as a primary method for uterine removal is superior to TAH.", "The present randomized study was undertaken in order to compare the short-term results between total laparoscopic hysterectomy and abdominal hysterectomy in a centre with experience in laparoscopic surgery. From January 1997 to September 1998 inclusive, 102 women aged 44-71 years were randomly assigned to either total laparoscopic hysterectomy (n = 51 patients) or abdominal hysterectomy (n = 51 patients). The patients' demographic characteristics were similar in both groups. Average intra-operative blood loss was lower in laparoscopic hysterectomy than in abdominal hysterectomy (P </= 0. 001). The average time employed for laparoscopic hysterectomy was 104.1 +/- 26.98 min; according to the learning curve experienced in this study, the range was 72-163 min and the results after the plateau was reached showed no statistical difference between laparoscopic and abdominal operating times. The mean length of hospital stay was 2.38 +/- 0.30 days in the laparoscopic hysterectomy group versus 6.23 +/- 1.85 days in the abdominal hysterectomy group (P </= 0.001). In conclusion, this study shows that total laparoscopic hysterectomy can be effectively performed within reasonable time limits, provided that operators are experienced surgeons in operative laparoscopy and that operating times are comparable with those of abdominal hysterectomy.", "To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial.\n Two parallel, multicentre, randomised trials.\n 28 UK centres and two South African centres.\n 1380 women were recruited; 1346 had surgery; 937 were followed up at one year. Primary outcome Rate of major complications.\n In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence interval 0.9% to 9.1%) and the number needed to treat to harm was 20. Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes) but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks after the operation, laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy (SF-12, body image scale, and sexual activity questionnaires). In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, -5.2% to 5.8%), and the number needed to treat to harm was 333. We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes) and was associated with a higher rate of detecting unexpected pathology (16.4% v 4.8%, P = < 0.01). However, this trial was underpowered.\n Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy. It also took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life. The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications; however, vaginal hysterectomy took less time.", "To compare the short-term results of the quality of life and satisfaction of patients submitted to total abdominal hysterectomy (TAH) and vaginal hysterectomy (VH) for benign uterine disease.\n Women referred for hysterectomy for uterine myoma were randomized to TAH (n=30) or VH (n=30). The exclusion criteria were uterine prolapse, indication associated surgical procedures and uterine size > or =300 cm3. After a month, follow-up questionnaires had a response rate of 100%, and consisted of an interview with application of SF-36 questionnaire (functional capacity, physical aspect and pain) and evaluation of satisfaction rate.\n There were no differences in the patients' mean age, parity, body mass index, preoperative hemoglobin levels and uterine size between groups. Lower postoperative quality-of-life scores were found in the TAH group when compared to the VH group in functional capacity (P=0.002), physical aspect (P=0.008) and pain (P=0.002). The general satisfaction rate with the surgery was similar in the two groups of patients (P=0.147). However, a higher rate of patients submitted to VH would choose the same therapeutic modality (65.5 vs 90%; P=0.021).\n A better postoperative quality of life (functional capacity, physical aspect and pain) and higher satisfaction rate was found in the VH when compared to TAH.", "To identify differences in the peri-operative outcome of women undergoing hysterectomy with bilateral salpingo-oophorectomy performed either by abdominal hysterectomy and bilateral salpingo-oophorectomy or by laparoscopic-assisted salpingo-oophorectomy and vaginal hysterectomy. To identify any potential management implications, including financial differences, between these two forms of operations.\n Eighty women undergoing hysterectomy and bilateral salpingo-oophorectomy for benign gynaecological conditions were prospectively randomised to have the procedure by laparoscopic-assisted bilateral salpingo-oophorectomy and vaginal hysterectomy or total abdominal hysterectomy and bilateral salpingo-oophorectomy. The peri-operative and post-operative courses of both groups were compared.\n Although laparoscopic-assisted bilateral salpingo-oophorectomy and vaginal hysterectomy took longer (100 (SD 5.6) versus 57 (SD 4.7) min, P < 0.0001), the women undergoing this procedure had a shorter time in hospital (3.5 versus six days, P < 0.0001) quicker recovery (three versus six weeks, P < 0.0001) and returned to work earlier. There were minimal complications in both groups and they were not significantly different. The cost of the laparoscopic-assisted procedure was greater during the operation with longer operating time and cost of disposable instruments. However, the total cost of treatment was less in this group because of shortened post-operative stay.\n The study shows laparoscopic-assisted bilateral salpingo-oophorectomy and vaginal hysterectomy is a safe and cost-effective procedure for women requiring a hysterectomy and bilateral salpingo-oophorectomy.", "Our purpose was to quantify and compare the metabolic and inflammatory changes after laparoscopic and abdominal hysterectomy.\n Forty-four patients with no major medical disease requiring abdominal hysterectomy for benign disorders were randomly assigned to have laparoscopic hysterectomy (n = 20) and abdominal hysterectomy (n = 24). Venous blood and 24-hour urine samples were collected the day before and for each of the first 3 postoperative days.\n No differences were present in demographic characteristics, operating time, and uterine weight between the two groups. No major complications were encountered. The laparoscopic hysterectomy group had a significantly lower postoperative morphine consumption (median 5.5 vs 14 mg, P < .05), lower febrile morbidity rate (15% vs 45.8%, P < .05), and shorter hospital stay (median 4 vs 6 days, P < .001) and demonstrated a less intense stress response in terms of serum interleukin-6 (median 50.6 vs 73.9 pg/mL x hour x 10, P = .01), C-reactive protein (median 28.1 vs 44.7 mg/L x hour x 10(2), P = .005), cortisol (median 23.4 vs 27.2 mg/mL x hour x 10(3), P = .04), white blood cell count (median 59.5 vs 69.8 10(9)/L x hour x 10, P = .009), 24-hour urinary excretion of cortisol (median 34.8 vs 44.2 nmol/L x hour x 10(3), P = .02), and norepinephrine (median 80.8 vs 132.4 nmol/L x hour x 10(2), P = .001). No significant difference was detected in plasma glucose (median 41.5 vs 45.6 mmol/L x hour x 10, P = 6) and 24-hour urinary excretion of epinephrine (median 32.2 vs 34.1 nmol/L x hour x 10(2), P = .3).\n Laparoscopic hysterectomy is associated with a lower morbidity and a less intense stress response than abdominal hysterectomy for benign diseases.", "To evaluate operative time, blood loss and inflammatory response in patients submitted to hysterectomy.\n Sixty patients referred for hysterectomy were prospectively randomized to total abdominal hysterectomy (n=20), vaginal hysterectomy (n=20), or laparoscopic hysterectomy (n=20). The operative time, blood loss (variation in erythrocyte and hemoglobin) and inflammatory answer (CRP and interleukin-6 dosages) were compared by using Kruskal-Wallis, Dunn non-parametric test and variance analysis with repeated measurements.\n Operative time was shorter for vaginal hysterectomy, and there was no significant difference between total abdominal hysterectomy and laparoscopic hysterectomy. Reduction in erythrocyte and hemoglobin was more noticeable after vaginal hysterectomy, followed by total abdominal hysterectomy and laparoscopic hysterectomy. CRP levels increased steadily from vaginal hysterectomy to laparoscopic hysterectomy and then to total abdominal hysterectomy. The increase in interleukin-6 was substantially higher in total abdominal hysterectomy, whereas no difference was noted between vaginal and laparoscopic hysterectomy.\n Vaginal hysterectomy presents superior results in terms of operative time and inflammatory response when compared with total abdominal and laparoscopic hysterectomy and it should be the first option for hysterectomy. Laparoscopic hysterectomy should be considered when the vaginal approach is unfeasible, showing clear advantages over abdominal hysterectomy.", "To compare laparoscopically assisted vaginal hysterectomy (LAVH) and total abdominal hysterectomy (TAH) in patients with uterine fibroids.\n A prospective randomised study.\n The San Paolo Hospital, Milan.\n Sixty-two patients, who were not suitable for a vaginal hysterectomy, requiring treatment for uterine fibroids.\n Randomisation between LAVH and TAH. Comparison of outcomes on the whole series, patients with uteri < or = 500 g (Group 1) and patients with uteri > 500 g (Group 2).\n To establish operating time, blood loss, complications, febrile morbidity, analgesics administration and hospital stay for both treatment approaches.\n Median uterine weight was 400 g in both LAVH and TAH group. Median operating time was longer for LAVH (135 min compared with 120 min for TAH; P = 0.001), but patients undergoing LAVH had less analgesics administration (23% compared with 77%, P < 0.001) and a shorter median hospital stay (3.8 compared with 5.8 days; P < 0.001). LAVH, when compared with TAH in the two weight subgroups, required a significantly longer operating time only in Group 2, significantly reduced analgesics administration only in Group 1, and significantly reduced hospital stay in both groups. Conversions of LAVH to laparotomy were significantly more frequent in Group 2 (3/11) than in Group 1 (0/20) (P = 0.04).\n Compared with TAH, LAVH has advantages in removing uteri weighing < or = 500 g, with comparable operating time, less post-operative pain and shorter recovery. Among uteri weighing > 500 g LAVH showed a shorter recovery, but longer operating time than TAH and a 27% rate of conversion to laparotomy.", "The purpose of this study was to compare peri-operative morbidity, preoperative sonographic estimation of uterine weight and postoperative outcomes of women with uterine fibroids larger than 6 cm in diameter or uteri estimated to weigh at least 450 g, undergoing either vaginal, laparoscopically assisted vaginal or abdominal hysterectomies.\n Ninety patients who met the criteria of uterine fibroids larger than 6 cm by ultrasonographic examination were included in our prospective study. Patients were randomized into laparoscopic-assisted vaginal hysterectomy (30 patients), vaginal hysterectomy (30 patients) and abdominal hysterectomy (30 patients) groups.\n The laparoscopically assisted vaginal hysterectomy group had significantly longer operative times than the abdominal and vaginal hysterectomy groups (109 +/- 22 min, 98 +/- 16 min, and 74 +/- 22 min, respectively, p < 0.001). Blood loss for vaginal hysterectomy was significantly lower than for either abdominal or laparoscopically assisted vaginal hysterectomies (215 +/- 134 ml, 293 +/- 182 ml, and 343 +/- 218 ml, respectively, p = 0.04). Vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy groups had shorter hospital stays, lower postoperative pain scores, more rapid bowel recovery and lower postoperative antibiotic use than the abdominal hysterectomy group. Uterine weight in the abdominal hysterectomy group was significantly heavier than in the vaginal and laparoscopically assisted vaginal hysterectomy groups (1020 +/- 383 g, 835 +/- 330 g, and 748 +/- 255 g, respectively, p = 0.02). We estimated that when a myoma measured between 8 and 10 cm, the uterus weighed approximately 450 g, and the sensitivity of this prediction was 57.5%. For a myoma larger than 13 cm, the estimated uterine weight was more than 900 g and the sensitivity of this prediction was 71%.\n The study shows vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy can be performed in women with uterine weight of at least 450 g. Preoperative ultrasonographic examination can provide the surgeon with valuable information on the size of the fibroid and the estimated weight of the enlarged uterus before implementing a suitable surgical method.", "To compare two techniques of hysterectomy.\n Prospective, randomised study.\n Institute for the Mother and Child Care, Prague.\n 85 patients randomized into two groups--laparoscopically assisted vaginal hysterectomy (LAVH) and total laparoscopic hysterectomy (TLH). The criteria studied were length of the procedure, blood loss, complication rate, uterus weight, rate of conversions, consumption of analgesics, inflammatory response.\n Mean length of the procedure for LAVH, TLH was 85 and 111 min, respectivelly, the mean blood loss 306 and 184 ml. There was no difference in inflammatory response and use of antibiotics. Consumption of analgesics was higher in the TLH group. Conversions to laparotomy occurred only in the LAVH group. Only in the TLH group we noticed serious postoperative complications.\n LAVH seems to be the preferable technique of hysterectomy for benign diseases of the uterus.", "To evaluate clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy.\n Fifty women scheduled for abdominal hysterectomy were randomized to undergo either laparoscopic (n = 25) or abdominal (n = 25) hysterectomy. Surgical characteristics, hospital stay, convalescence and complications were analyzed. Blood samples for assay of markers of tissue trauma (interleukin-6, C-reactive protein, tumor-associated trypsin inhibitor and tumor-associated antigen CA 125) were taken preoperatively, on the first, second and seventh postoperative day and at the follow-up visit four weeks after surgery.\n In uncomplicated hysterectomies (n = 18) the operating time (85.3 min versus 57.5 min, p < 0.00001) was longer for laparoscopic group but the hospital stay (2.1 days versus 3.4 days, p < 0.00001) and sick leave (21.4 days versus 38.5 days, p < 0.00001) were shorter in the laparoscopic group. Postoperative increases in all markers were significant in both groups. The interleukin-6 concentration was highest on the first postoperative day in both groups, that of C-reactive protein on the second postoperative day in both groups, tumor-associated trypsin inhibitor on the seventh postoperative day in the laparoscopic group and on the second postoperative day in the abdominal group and tumor-associated antigen CA 125 on the seventh postoperative day in both groups. Both interleukin-6 and C-reactive protein levels were lower in the laparoscopic group on the first (p = 0.01 and p = 0.03, respectively) and on the second postoperative day (p = 0.02 and p < 0.001, respectively) compared with the abdominal group. No differences were seen in tumor-associated trypsin inhibitor and tumor-associated antigen CA 125 levels between the groups.\n Laparoscopic hysterectomy should replace abdominal hysterectomy whenever possible because of a more favorable clinical outcome and less tissue trauma.", "To determine under controlled conditions whether there are significant differences in the duration of hospitalization and recovery between abdominal and vaginal hysterectomy for indications other than uterovaginal prolapse.\n In a two-center prospective, double-blind randomized trial, 36 women with dysfunctional uterine bleeding, uterine fibroids or pelvic pain scheduled for hysterectomy were randomized to abdominal or vaginal hysterectomy. The primary outcome measure was the duration of hospital stay. Secondary outcome measures included analgesic requirements and return to normal health and function.\n There were no significant differences in peri-operative patient or surgical characteristics. Vaginal hysterectomy was associated with a reduction in hospital stay compared to abdominal hysterectomy (median stay 3 days vs. 5 days, p = 0.01). In addition, patients undergoing vaginal hysterectomy had reduced analgesic requirements (mean 75.4 mg vs. 131.4 mg morphine equivalent, p = 0.002), shorter need for intravenous hydration (mean 25.3 h vs. 32.7 h, p = 0.05), and faster return of bowel action (median 3 days vs. 4 days, p = 0.002). They also returned to normal domestic activities (mean 4.6 weeks vs. 8.5 weeks, p = 0.01) and work (mean 7.0 weeks vs. 13.9 weeks, p = 0.005), and completed their recovery (mean 7.9 weeks vs. 16.9 weeks, p = 0.008) more quickly.\n Vaginal hysterectomy was associated with significant benefits in terms of reduced hospital stay and improved patient recovery. Vaginal hysterectomy should be the route of choice not only for women with genital tract prolapse but also those without.", "To detect differences in clinical short term outcome between total abdominal hysterectomy, vaginal hysterectomy and laparoscopic assisted vaginal hysterectomy.\n Randomised controlled trial.\n Department of Obstetrics and Gynaecology, Hospital of Helsingborg, Sweden.\n One hundred-twenty women scheduled for hysterectomy for various indications.\n Randomisation into three treatment arms: total abdominal hysterectomy (n = 40); vaginal hysterectomy (n = 40) and laparoscopic assisted vaginal hysterectomy (n = 40). During traditional abdominal and vaginal surgery, laparoscopic assistance was kept to a minimum. Substantial number of cases needed volume-reducing manoeuvres due to uterine size.\n Duration of surgery, anaesthesia, time in hospital and recovery time.\n Mean duration (range) of surgery was significantly longer for laparoscopic assisted vaginal hysterectomy compared with vaginal hysterectomy and total abdominal hysterectomy, 102 min (50-175), 81 min (35-135) and 68 min (28-125), respectively. Mean stay in hospital and mean time to recovery was significantly longer for total abdominal hysterectomy compared with vaginal hysterectomy and laparoscopic assisted vaginal hysterectomy. The difference between vaginal hysterectomy and laparoscopic assisted vaginal hysterectomy was not significant. It was possible to remove uteri under 600 g with all three methods. Four laparoscopic assisted vaginal hysterectomies and one vaginal hysterectomy were converted to open surgery. Reoperation and blood transfusion were required after two vaginal hysterectomies and one laparoscopic assisted vaginal hysterectomy. One woman needed blood transfusion after total abdominal hysterectomy.\n Traditional vaginal hysterectomy proved to be feasible and the faster operative technique compared with vaginal hysterectomy with laparoscopic assistance. The abdominal technique was somewhat faster, but time spent in theatre was not significantly shorter. Abdominal hysterectomy required on average a longer hospital stay of one day and one additional week of convalescence compared with traditional vaginal hysterectomy. Vaginal hysterectomy should be a primary method for uterine removal.", "This study was undertaken to compare morbidity for women undergoing laparoscopy-assisted vaginal hysterectomy with bilateral oophorectomy (LAVHO) and vaginal hysterectomy with bilateral oophorectomy without laparoscopic assistance (VHO).\n Between April 1, 2002, and February 1, 2004, a prospective randomized study at Marseille University Hospital (La Conception) included 48 patients who underwent a hysterectomy with prophylactic bilateral oophorectomy for benign uterine conditions. These patients were allocated to 2 groups (LAVHO vs VHO). The study variables were duration of surgery and of hospitalization and surgical and postoperative complications.\n There was no significant difference in the duration of surgery between the LAVHO and VHO groups (100.2 +/- 27.9 vs 83.9 +/- 34.6, P = .08). The rate of complications was significantly higher in the LAVHO group (13/24 [54.1%] vs 6/24 [25%], P = .039).\n The overall complication rate was higher with LAVHO than VHO. It thus appears that laparoscopic assistance is not useful in performing vaginal hysterectomies with prophylactic bilateral oophorectomies in patients without other related disorders (endometriosis, adhesions, adnexal anomalies).", "To compare laparoscopic hysterectomy and abdominal total hysterectomy regarding influence on postoperative psychological wellbeing and surgical measures.\n A prospective, open, randomised multicentre trial.\n Five hospitals in the South East of Sweden.\n Hundred and twenty-five women scheduled for hysterectomy for benign conditions were enrolled in the study, and 119 women completed the study. Fifty-six women were randomised to abdominal hysterectomy and 63 to laparoscopic hysterectomy.\n Psychometric tests measuring general wellbeing, depression and anxiety preoperatively and 5 weeks and 6 months postoperatively.\n Effects of operating method on the psychological wellbeing postoperatively. Analysis of data regarding operating time, peroperative and postoperative complications, blood loss, hospital stay and recovery time.\n No significant differences in the scores were observed between the two groups in any of the four psychometric tests. Both the surgical methods were associated with a significantly higher degree of psychological wellbeing 5 weeks postoperatively compared with preoperatively. The operating time was significantly longer for the laparoscopic hysterectomy group, but the duration of the stay in hospital and sick-leave were significantly shorter for laparoscopic hysterectomy group compared with the abdominal hysterectomy group.\n General psychological wellbeing is equal after laparoscopic and abdominal hysterectomy within 6 months after the operation. The advantages of the laparoscopic hysterectomy are the shorter stay in hospital and shorter sick-leave, but these issues must be balanced by a longer duration of the operation.", "The aim of this study was to evaluate pain and pulmonary function the first two days after abdominal and laparoscopic hysterectomy.\n Women scheduled for abdominal hysterectomy were prospectively randomized to either laparoscopic (n=20) or abdominal (n=20) hysterectomy. Analgesics were self-administered by the patients by means of a programable infusion pump containing morphine. Postoperative pain was evaluated using a visual analog scale. Oxygen saturation was measured with an oxymeter. Pulmonary function was assessed using a peak flow meter measuring peak expiratory flow and a vitalograph measuring forced vital capacity and forced expiratory volume in one second.\n Pain scores were lower after laparoscopic hysterectomy at the first (p<0.05) and second postoperative day (p<0.01). Lung function was impaired on days 1 and 2 postoperatively, measured as peak expiratory flow, forced vital capacity and forced expiratory volume in one second, in both groups compared to the preoperative values. The patients undergoing laparoscopic hysterectomy had less impairment of lung function measured by peak expiratory flow (p<0.01), forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.05) the first postoperative day compared to the patients undergoing abdominal hysterectomy. The second postoperative day differences between the groups remained for peak expiratory flow (p<0.05) and forced expiratory volume in one second (p<0.05).\n Laparoscopic hysterectomy results in less pain and less impairment of respiratory function compared to abdominal hysterectomy.", "We compare the surgical results of 60 women undergoing laparoscopically assisted vaginal hysterectomy (LAVH) and 41 having total laparoscopic hysterectomy (TLH) under the indications of uterine fibroids or adenomyosis. With similar specimen weight, TLH required longer surgery duration (140.4 vs. 115.1 min; p < 0.05) than LAVH. Among women with uteri weighing <or=200 g, TLH resulted in relatively smaller blood loss with comparable operating time (115.6 vs. 116.0 min for LAVH; p > 0.05) although the TLH group had a significantly higher rate of previous abdominal surgery (57.7 vs. 20%; p < 0.05). There were no significant differences between the two groups with respect to the mean cost, length of hospital stay and rate of various complications (p > 0.05). As for sexual symptoms, dyspareunia decreased significantly post-operatively in the LAVH group (p < 0.05), but not in the TLH group. A significant reduction in the frequency of orgasms after surgery was detected in both groups (p < 0.05). In conclusion, LAVH has advantages over TLH with reduced operating time. Although it is a technical challenge, TLH can be effectively performed within reasonable time limits in selected cases. The effects on sexual function, following either LAVH or TLH, are found to be similar.\n Copyright 2002 S. Karger AG, Basel", "Technique and Results: The aim of this prospective randomised study was to compare laparoscopy-assisted vaginal hysterectomy (LAVH, group A) with abdominal hysterectomy (abd. HE, group B). Therefore, 35 hysterectomies due to non-malignant diseases such as uterine fibroma were performed in each group. A rather simple technique of LAVH was developed. In respect of the indication for hysterectomy, mean duration of operation and the size of the excised uteri there were no statistical differences between the two groups. One severe complication of haemorrhage was observed after LAVH in a patient suffering from a coagulopathy. The requirements for analgesics were significantly lower after LAVH compared to abd. HE during the postoperative period. A significantly lower serum concentration of the c-reactive protein on the first and third days after operation was found in group A. The patients of group A were discharged on the average 5 days after operation and 11 days in group B, respectively. Hence LAVH should replace abd. HE in most cases with the advantages of shorter hospitalisation, minimised requirements for analgesics and cost reduction.", "The purpose of this study was to compare advantages, disadvantages, and outcomes in patients who undergo vaginal or abdominal hysterectomy for enlarged symptomatic uteri.\n In a prospective, randomized study, 60 vaginal hysterectomies (study group) were compared with 59 abdominal hysterectomies (control group); all of the hysterectomies were performed for symptomatic uterine fibroids from January 1997 through December 2000. We excluded from the study the other common causes of hysterectomy such as prolapse, bleeding, adenomyosis, and endometrial or cervical carcinoma. In both groups, uterine weights ranged from 200 g to 1300 g. For enlarged uteri, vaginal hysterectomies were performed with the use of volume reduction techniques: Intramyometrial coring, corporal bisection, and morcellation. The evaluated parameters included patient age, weight, parity, uterine weight, operative time, blood loss, demand for analgesics, eventual surgical complications, length of admission, and hospital charges. The Mann-Whitney U test and chi(2) tests were applied for statistical analysis. Probability values of <.05 were considered statistically significant.\n There were no major differences in patient age, weight, parity, and uterine weight between the two groups. Operative time was significantly lower for the vaginal route as compared with the abdominal route (86 minutes vs 102 minutes, P <.001). No intraoperative complications were noted both in the study and control groups or the control group. Surgical bleeding (expressed by hemoglobin loss) was not significantly different between the two groups. In the postoperative period, we found a higher incidence of fever (30.5% vs 16.6%, P <.05) and demand for analgesics (86% vs 66%, P <.05) in the abdominal group as compared with the vaginal group. Significant advantages of vaginal hysterectomy were a reduction in the hospital stay (3 days vs 4 days, P <.001) and cost.\n These results should lead to the choice of vaginal hysterectomy as a valid alternative to the abdominal hysterectomy, even for enlarged uteri.", "To compare short term clinical results in a prospective randomised trial of laparoscopic hysterectomy compared with abdominal hysterectomy.\n One hundred and forty-three women scheduled for total abdominal hysterectomy, with or without salpingo-oophorectomy and with a maximum uterine width of less than ll cm, were prospectively randomised to undergo the procedure by laparoscopic hysterectomy (n = 71) or abdominal hysterectomy (n = 72). During laparoscopic hysterectomy, the uterine arteries as well as the upper portion of the cardinal ligaments were transected laparoscopically. The perioperative and post-operative courses of the groups were compared.\n The number of women with a complication did not differ significantly between laparoscopic hysterectomy (27%) and abdominal hysterectomy (33%) groups. The post-operative fall in erythrocyte volume fraction was significantly greater following abdominal hysterectomy (5.6% compared with 4.1% median value, P < 0.001). Post operative pain, assessed by the patients two days after surgery on a visual analogue scale, was significantly higher following abdominal hysterectomy (4.2 compared with 3.6 units median value, P < 0.05). Although laparoscopic hysterectomy took longer (148 min compared with 85 min median value, P < 0.001), the women undergoing this procedure had a shorter post-operative time in hospital (two compared with four days median value, P < 0.001) and a shorter convalescence (16 compared with 35 days median value, P < 0.001).\n Laparoscopic hysterectomy is a safe procedure for selected patients scheduled for abdominal hysterectomy, and offers benefits to the patients in the form of less operative bleeding, less post-operative pain, shorter time in hospital and shorter convalescence time.", "Laparoscopic-assisted vaginal hysterectomy (LAVH) can be used for the vaginal removal of large uteri (200 g), which are conventionally treated with an abdominal approach (AH).\n Forty-eight women with a sonographically estimated uterine weight of >200 g were prospectively randomized to undergo either LAVH (n = 28) or AH (n = 20).\n The median uterus weight was 334 g for LAVH vs 428 g for AH (not significant). The median operative time (133 vs 132 min) and duration of recuperation (42 vs 42 days) were similar. LAVH was associated with significantly less intraoperative blood loss (median, 200 vs 600 ml; p < 0.05), a lower pain index at postoperative day 4 (median [who scale], 0 VS 5; P < 0.05), a lower decrease in hemoglobin (median,-0.6 VS -1.55 MG/DL; P < 0.05), and a lower decrease in hematocrit (median, -0.03% VS -0.07%; P < 0.05). There were no significant differences in the frequency of postoperative complications (14.3% for LAVH VS 30% for AH). Although all LAVH patients who answered the questionnaire said they would undergo the same procedure again, only 45% of the AH group were satisfied (P < 0.05).\n For the treatment of uteri >200 g, LAVH has several advantages over AH: lower postoperative morbidity, quicker short-term recuperation, and better patient acceptance.", "To compare intraoperative and postoperative outcomes between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy among patients who are not eligible for vaginal hysterectomy.\n Study subjects were randomly assigned to undergo laparoscopically assisted vaginal hysterectomy or standard abdominal hysterectomy. Intraoperative and postoperative management was similar for each group. Surgical characteristics, complications, length of hospital stay, charges, and convalescence were analyzed.\n Sixty-five women at three institutions underwent laparoscopically assisted vaginal hysterectomy (n = 34) or abdominal hysterectomy (n = 31). Three patients in the laparoscopic group required conversion to abdominal hysterectomy. Mean operating time was significantly longer for laparoscopically assisted vaginal hysterectomy (179.8 versus 146.0 minutes). There were no differences in blood loss or incidence of intraoperative complications. There was a higher incidence of wound complications in the abdominal hysterectomy group, but no significant difference in the frequency of postoperative complications. Laparoscopically assisted vaginal hysterectomy required a significantly shorter mean hospital stay (2.1 days) and convalescence (28.0 days) than abdominal hysterectomy (4.1 days and 38.0 days, respectively). There were no significant differences in mean hospital charges between the study groups (laparoscopic $8161, abdominal $6974).\n Except for operating time, there are no differences between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy regarding intraoperative characteristics among abdominal hysterectomy candidates. Postoperatively, laparoscopically assisted vaginal hysterectomy requires a shorter hospital stay and convalescence. Hospital charges are similar between the procedures. A larger number of cases will help determine the indications for laparoscopically assisted vaginal hysterectomy.", "To evaluate in a prospective series whether, even in presence of a large uterus, total laparoscopic hysterectomy is feasible and safe, and may be substituted for abdominal hysterectomy.\n Randomized comparison (Canadian Task Force classification I). Setting. Center for Reconstructive Pelvic Endosurgery, Bologna, Italy.\n One hundred twenty-two women with large uterus (>14 wks' gestation) caused by myomas.\n Total laparoscopic hysterectomy and total abdominal hysterectomy.\n Sixty women underwent laparoscopic hysterectomy (group 1) and 62 abdominal hysterectomy (group 2). Mean longitudinal diameter of the uterus, mean number and diameter of myomas, operating time, and average drop in hemoglobin were similar in the groups. One conversion to laparotomy was necessary because of a bowel injury in a patient with severe pelvic adhesions. Cystotomy occurred in one woman in group 2 and was immediately repaired. Febrile morbidity was statistically more frequent in group 2 than in group 1. Postoperative hospitalization and convalescence were statistically shorter in group 1.\n Laparoscopic hysterectomy is safe and feasible even in the presence of large uterus, and is a valid alternative to abdominal hysterectomy when the vaginal route is contraindicated.", "Minimally invasive surgery aims to achieve at least a similar clinical effectiveness with a quicker recovery than traditional open techniques. Although there have been numerous randomized clinical trials comparing laparoscopic hysterectomy with hysterectomy by laparotomy, only a few studies have compared quality of life after different types of hysterectomy. None of these studies evaluated total laparoscopic hysterectomy. In this paper, we report on a randomized comparison of quality of life after total laparoscopic versus total abdominal hysterectomy.\n Randomized, controlled trial (Canadian Task Force classification I).\n Single-center teaching hospital in The Netherlands.\n Patients scheduled for hysterectomy for a benign condition, in whom a vaginal hysterectomy was not possible and laparoscopic hysterectomy was feasible (mobile uterus not exceeding the size of 18 weeks' gestation).\n Abdominal versus laparoscopic hysterectomy.\n Patients completed the Dutch version RAND-36 health survey preoperatively as well as at 5 time points in the first 12 weeks after surgery. The primary outcome of the study was quality of life as measured by the RAND-36. A linear mixed model was used for statistical analysis while accounting for baseline values. Secondary outcomes were hospital stay and complications. There were 88 patients eligible, of whom 59 gave consent for randomization. Twenty-seven women were allocated to the laparoscopic arm and 32 to the abdominal arm. We found a significant treatment effect favoring laparoscopic hysterectomy in the RAND-36 scale for vitality. Laparoscopic hysterectomy performed better on all other scales of the RAND-36, but these differences were not statistically significant.\n Laparoscopic hysterectomy results in more postoperative vitality when compared with abdominal hysterectomy. For this reason, all women with a benign condition requiring abdominal hysterectomy, in whom the laparoscopic approach is feasible, should have the chance to choose laparoscopic hysterectomy.", "Laparoscopic hysterectomy (LH) is a way to avoid laparotomy. However, there is evidence that most women treated by abdominal hysterectomy are suitable for vaginal surgery. To test this hypothesis, and to determine the relative merits of laparoscopic and vaginal hysterectomy (VH) and the best technique for LH, we prospectively studied 98 women who had relative contraindications for vaginal surgery by traditional criteria. 75 underwent LH and 23 VH. The LH group included 22 women who had been assigned to this route of surgery as part of a prospective randomised controlled comparison with VH (23 women). Surgery was completed with the intended technique in 93.9% of cases. 5 women in the LH group (6.7%) and 2 in the VH group required laparotomy or additional procedures. In the prospective randomised study LH took longer than VH (mean duration 131 vs 77 min). VH was the faster procedure, irrespective of uterine size and need for oophorectomy. With LH, the operative time increased as more of the hysterectomy was carried out with laparoscopic rather than vaginal dissection. Complication rates, blood loss, analgesia requirements, and recovery were similar for the two techniques. Our study confirms that most hysterectomies could be performed vaginally, and that LH is a much slower procedure. If LH is done, it should be converted to a vaginal procedure as early as possible to reduce the overall operating time. LH does seem to be a waste of time for most patients.", "The aim of the study was to compare the effects of total laparoscopic hysterectomy with those of vaginal hysterectomy.\n We conducted a prospective randomised trial on 400 patients who agreed to be randomized to either laparoscopic total hysterectomy or vaginal hysterectomy. They were monitored for one year to evaluate the rate of major complications and the results on quality of life.\n Total laparoscopic hysterectomy was associated with a higher rate of major haemorrhages and ureteric injuries than vaginal hysterectomy (7% vs 2.5% and 2.5% vs 0%; P<0.05) only during the first year of study according to a normal learning-curve. It took longer to perform (85.9 min vs 46.6 min), but was less painful (visual analogue scale 5.3 vs 6.0; P<0.01) and there was a shorter stay in hospital after the operation (2.9 vs 3.3 days). Six weeks after the operation, total laparoscopic hysterectomy was associated with less pain and better quality of life than vaginal hysterectomy (SF-12).\n Total laparoscopic hysterectomy was associated with a significantly higher rate of major haemorrhages and ureteric injuries than vaginal hysterectomy only during the first year of study according to a normal learning-curve. It took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life.", "To evaluate short-term recovery of vaginal hysterectomy with those of laparoscopic assisted vaginal hysterectomy performed in a prospective, randomized multicentric study.\n Eighty patients referred for hysterectomy for benign pathology were randomized to either vaginal hysterectomy (40 patients) or laparoscopic assisted vaginal hysterectomy (40 patients). Inclusion criteria were uterine size larger than 280 g and one or more of the following: previous pelvic surgery, history of pelvic inflammatory disease, moderate or severe endometriosis, concomitant adnexal masses, and indication for adnexectomy. No upper limit of uterine size was set. All the laparoscopic and the vaginal hysterectomies were done under endotracheal general anesthesia.\n There was no statistically significant difference in terms of patient's age, parity, postmenopausal state, indication for surgery and mean uterine weight between the 2 groups. Laparoconversion was performed in three women in the laparoscopic group. Operative time was significantly shorter in the vaginal versus the laparoscopic groups 108+/-35 and 160+/-50 respectively (p<0.001). The use of paracetamol, non steroidal anti-inflammatory drugs, and opioid during hospitalization were similar in the 2 groups. There was no difference in the 1st day hemoglobin level drop, time of passing gas and stool, or hospital stay between the 2 groups.\n In contrast with earlier reports, there was no difference in short-term recovery between patients undergoing vaginal or laparoscopic hysterectomy. No advantage was found performing laparoscopic assisted vaginal hysterectomy in comparison with the standard vaginal hysterectomy.", "The aim of this study was to compare operative and early postoperative outcomes of laparoscopic-assisted vaginal hysterectomy (LAVH) and minilaparotomy in a randomized clinical trial including patients undergoing total hysterectomy for benign gynecologic disease and having 1 or more of the generally considered contraindications to vaginal route.\n Prospective, randomized, multicenter trial (Canadian Task Force classification I).\n Departments of Gynecology from 3 major university hospitals in Rome.\n Eighty-one patients who were candidates for abdominal hysterectomy.\n Laparoscopic-assisted vaginal hysterectomy and minilaparotomy hysterectomy.\n Forty patients were randomized to LAVH and 41 to minilaparotomy. Characteristics of patients and indications for surgery in the 2 arms were comparable. In the minilaparotomy group, complications were as follows: 1 case (2.4%) of delayed laparotomy with 2 units of red blood cell transfusion, 2 cases (4.8%) of wound infection, and 3 cases (7.3%) of fever of unknown origin. No minor or major complications were observed in the LAVH group. Postoperative visual analog scale pain scores at days 1 and 2 were significantly lower in the LAVH group (p <.05). The complication rate between the 2 groups was significantly lower for LAVH (p = .026).\n Because LAVH was associated with significantly lower early postoperative pain scores and complication rates, in general LAVH should be preferred to minilaparotomy hysterectomy when the vaginal approach cannot be used.", "To compare short-term results of vaginal hysterectomy (VH) with those of laparoscopically assisted vaginal hysterectomy (LAVH) in women with enlarged uteri.\n Eighty women referred for abdominal hysterectomies for benign disease were assigned randomly to vaginal hysterectomy or LAVH. Inclusion criteria were uterine size larger than 280 g and one or more of the following traditional contraindications of vaginal hysterectomy: previous pelvic surgery, history of pelvic inflammatory disease, moderate or severe endometriosis, concomitant adnexal masses, indication for adnexectomy, and nulliparity without uterine descent.\n There were no differences in patients' mean age, parity, rate of postmenopausal state, previous pelvic surgery, preoperative hemoglobin levels, and mean uterine weight. Indications for surgery were similar between groups. No difference was found in the mean +/- standard deviation (SD) uterine weight (range) between vaginal hysterectomy and LAVH groups (424 +/- 211 g [280--930 g] and 513 +/- 360 g [290--1560 g]), respectively. Except for one bladder injury in the laparoscopic group (injury treated laparoscopically), there were no other major complications. Complication rates in vaginal and laparoscopic groups were 15% and 37.5%, respectively (P <.05). Mean operating time was shorter in the vaginal than the laparoscopic group (108 +/- 35 minutes and 156 +/- 50 minutes, respectively [P <.001]). There was no difference in first day hemoglobin level drops or hospital stays between groups.\n Vaginal hysterectomy can be successful even in women with enlarged uteri and other conditions considered by some to contraindicate the operation. Laparoscopically assisted vaginal hysterectomy offered no advantages over the standard vaginal hysterectomy.", "The objective of this study was to evaluate short-term results of laparoscopically assisted vaginal hysterectomy with those of total abdominal hysterectomy in a prospective, randomized, multicenter study.\n One hundred sixteen patients referred for abdominal hysterectomy were randomized to either laparoscopically assisted vaginal hysterectomy (58 patients) or abdominal hysterectomy (58 patients). Inclusion criteria were one or more of the following, where a vaginal hysterectomy would be traditionally contraindicated: uterine size larger than 280 g, previous pelvic surgery, history of pelvic inflammatory disease, moderate or severe endometriosis, concomitant adnexal masses or indication for adnexectomy, and nulliparity with lack of uterine descent and limited vaginal access. An upper limit of uterine size was set at 16 weeks' gestation (ie, 700 g).\n There were no differences in terms of patient's age, parity, preoperative hemoglobin levels, mean uterine weight, and total operating time between the 2 groups. Estimated blood losses and postoperative day 1 hemoglobin drop were significantly lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy (P<.05). There were 1 major and 2 minor complications in the laparoscopically assisted vaginal hysterectomy group compared with 2 major and 5 minor complications in the abdominal hysterectomy group (P not significant). Postoperative pain was lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy on postoperative days 1, 2, and 3 (P<.05). Postoperative hospital stay was significantly shorter for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy (P<.001).\n The present study demonstrates that, given adequate training in laparoscopic surgery, laparoscopically assisted vaginal hysterectomy may replace abdominal hysterectomy in most patients who require a hysterectomy and have contraindications to vaginal hysterectomy, with all the benefits associated with the vaginal route.", "The objective of this study was to compare the results of a modified laparoscopically assisted vaginal hysterectomy (LAVH) procedure, using light-endorsed transvaginal section by two puncture trocars, with those of total abdominal hysterectomy (TAH) in a prospective, randomized, short-term study. A new, modified LAVH technique using Endo GIA stapler and two puncture trocars was established. For the laparoscopic phase, each adnexum was dissected, and the vesicouterine junction was identified clearly with the laparoscopic light from the vaginal side. Vaginal-phase surgery was performed as usual. Two hundred patients scheduled for abdominal hysterectomy were randomized to either LAVH (n = 100) or TAH (n = 100). Duration of hospitalization, time of surgery, dose of analgesics, and rates of complications were significantly lower in the LAVH group (p < 0.001). The average operating time was 77 +/- 30 min for LAVH and 102 +/- 18 min for TAH. The duration of hospitalization was 3.2 +/- 0.7 days for LAVH and 5.5 +/- 1.3 days for TAH. There were three complications in the LAVH group and 15 in the TAH group. Postoperative meperidine requirements (1.2 vs. 3.7 ampoules, 1 ampoule = 50 mg) were significantly fewer in the LAVH group. Regarding the training time, the mean operating time in the first 20 cases was 98 min, and in the last 20 cases it was 70.9 min. As compared with TAH and other modified LAVH procedures reported previously, the present technique is easy to learn and timesaving with fewer complications.\n Copyright 2003 S. Karger AG, Basel" ]

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[ "The effect of a programme of organised and supervised peer support on the initiation and duration of breastfeeding: a randomised trial.", "[Educational intervention on breastfeeding promotion to the Family Health Program team].", "Nursing intervention to increase the duration of breastfeeding.", "Comparison of the effect of two systems for the promotion of exclusive breastfeeding.", "Evaluating the effect of a breastfeeding consultant on the duration of breastfeeding.", "Antenatal education and postnatal support strategies for improving rates of exclusive breast feeding: randomised controlled trial.", "Effect of intervention to improve breastfeeding technique on the frequency of exclusive breastfeeding and lactation-related problems.", "Effects of home visits and telephone contacts on breastfeeding compliance in Taiwan.", "Exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa (PROMISE-EBF): a cluster-randomised trial.", "Efficacy of home-based peer counselling to promote exclusive breastfeeding: a randomised controlled trial.", "Factors related to breastfeeding duration.", "Home breastfeeding support by health professionals: findings of a randomized controlled trial in a population of Italian women.", "The effect of a postnatal education and support program on breastfeeding among primiparous women: a randomized controlled trial.", "Effect of early postnatal breastfeeding support: a cluster-randomized community based trial.", "[Controlled study of a regular telephone support program given by volunteers on the establishment of breastfeeding].", "Training peer counselors to promote and support exclusive breastfeeding in Bangladesh.", "Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.", "Randomised controlled trial of support from volunteer counsellors for mothers considering breast feeding.", "Effectiveness of home-based peer counselling to promote breastfeeding in the northeast of Brazil: a randomized clinical trial.", "A breast-feeding promotion and support program a randomized trial in The Netherlands.", "Home versus hospital breastfeeding support for newborns: a randomized controlled trial.", "Effect of an extended midwifery postnatal support programme on the duration of breast feeding: a randomised controlled trial.", "A pilot randomized controlled trial of a breastfeeding self-efficacy intervention with primiparous mothers.", "[Promotion of breast-feeding in urban localities of southern Brazil: a randomized intervention study].", "Lactation nurse increases duration of breast feeding.", "The influence of additional information, advice and support on the success of breast feeding in working class primiparas.", "Costs and effectiveness of community postnatal support workers: randomised controlled trial.", "Counseling and motivational videotapes increase duration of breast-feeding in African-American WIC participants who initiate breast-feeding.", "[Promotion of breastfeeding: the importance of pediatricians with specific training].", "Postnatal home visits in teenage mothers: a randomised controlled trial.", "A prospective study of individual courses of breast feeding.", "Breastfeeding duration, costs, and benefits of a support program for low-income breastfeeding women.", "Effectiveness of exclusive breastfeeding promotion in low-income mothers: a randomized controlled study.", "Effect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trial.", "Dads as breastfeeding advocates: results from a randomized controlled trial of an educational intervention.", "Randomized, controlled trial of a prenatal and postnatal lactation consultant intervention on duration and intensity of breastfeeding up to 12 months.", "Randomized trial of postpartum care after hospital discharge.", "Does continuity of care by well-trained breastfeeding counselors improve a mother's perception of support?", "Maternal and infant health problems after normal childbirth: a randomised controlled study in Zambia.", "The effect of individualized professional support on duration of breastfeeding: a randomized controlled trial.", "Lactation counseling increases exclusive breast-feeding rates in Ghana.", "Effect of breastfeeding education on the feeding pattern and health of infants in their first 4 months in the Islamic Republic of Iran.", "Efficacy of breastfeeding support provided by trained clinicians during an early, routine, preventive visit: a prospective, randomized, open trial of 226 mother-infant pairs.", "Assignment to a hospital-based breastfeeding clinic and exclusive breastfeeding among immigrant Hispanic mothers: a randomized, controlled trial.", "Lactation counseling increases breast-feeding duration but not breast milk intake as measured by isotopic methods.", "Differential response to an exclusive breastfeeding peer counseling intervention: the role of ethnicity.", "Maternal dietary counseling in the first year of life is associated with a higher healthy eating index in childhood.", "The effect of postpartum lactation counseling on the duration of breast-feeding in low-income women.", "Effectiveness of policy to provide breastfeeding groups (BIG) for pregnant and breastfeeding mothers in primary care: cluster randomised controlled trial.", "The effect of postnatal breastfeeding education/support offered at home 3 days after delivery on breastfeeding duration and knowledge: a randomized trial.", "Effect of postnatal home visits on maternal/infant outcomes in Syria: a randomized controlled trial.", "A randomized controlled community-based trial to improve breastfeeding rates among urban low-income mothers.", "The effect of peer support on breast-feeding duration among primiparous women: a randomized controlled trial." ]

[ "Peer support may improve breastfeeding rates but the evidence is inconclusive. Previous studies and reviews recommend trials in different healthcare settings.\n To test if a specified programme of peer support affects the initiation and/or the duration of breastfeeding.\n A two-group randomised controlled trial of peer support for breastfeeding with evaluation of breastfeeding initiation and duration on an intention-to-treat basis.\n General practice in Ayrshire, Scotland.\n Following informed consent, 225 women at 28 weeks gestation were allocated to control or peer support group by post-recruitment concealed allocation. All peer support and control group mothers received normal professional breastfeeding support. Additionally, those in the peer support group still breastfeeding on return home from hospital had peer support until 16 weeks.\n Thirty-five of the 112 (31%) women in the peer support group were breastfeeding at 6 weeks compared to 33/113 (29%) in the control group, a difference of 2% (95% confidence interval = -10% to 14%). The median breastfeeding duration for all women in the peer support group was 2 days compared to 1 day for the control group and the Kaplan-Meier survival plot shows the peer support group overall breastfeeding slightly longer than the control group, with no statistically significant difference by logrank test (P = 0.5). The median breastfeeding duration among primagravidae in the peer support group was 7 days, compared to 3 days for the control group. Among women who started to breastfeed the medians were 72 days in the peer support group and 56 days in the control group. These differences were not statistically significant.\n Peer support did not increase breastfeeding in this population by a statistically significant amount.", "Breastfeeding Friendly Primary Care Initiative comprises educational activities focused on primary care units. The To evaluate the effectiveness of a strategy on breastfeeding promotion to the Family Health Program team.\n A controlled intervention study was performed with 20 family health care teams randomly selected into intervention and control group in Montes Claros, Southeastern Brazil, in 2006. The teams randomly selected into intervention and control group, and the intervention group took part in a 24-hour training program on breastfeeding promotion for health providers, modeled on the Baby-Friendly Hospital Initiative. It was emphasized health provider's support for breastfeeding and management of major lactation problems. The control group received routine breastfeeding training. Mothers of all children under two cared by the teams were interviewed at home before (n=1,423) and 12 months after the intervention (n=1,491) and answered questions about breastfeeding practices. Survival curves of breastfeeding were plotted and compared for both time points studied using the log rank test.\n There was a significant increase in exclusive breastfeeding after the educational activities for the Family Health Program teams. Survival curves of exclusive breastfeeding at the fi rst time point studied showed no statistical significance difference between the groups by log rank test (p=0.502). After the intervention, survival curves of exclusive breastfeeding were significantly different by the log rank test (p=0.001).\n The training of Family Health Program teams as proposed by the Baby-Friendly Hospital Initiative proved to be an effective, low-cost strategy for raising awareness among health providers, providing consistent information, and assuring the required support to mothers with breastfeeding issues.", "nan", "Promotion of breastfeeding is an important child-survival intervention, yet little is known about which promotional strategies are the most effective. We aimed to compare the effects on rates of breastfeeding of two systems for promotion of breastfeeding in Brazil--a hospital-based system and the same system combined with a programme of home visits.\n In February, 2001, maternity staff from two hospitals in Pernambuco, Brazil, were trained according to the Baby-Friendly Hospital Initiative (BFHI). In a randomised trial between March and August, 2001, 350 mothers giving birth at these hospitals were assigned ten postnatal home visits to promote and support breastfeeding (n=175) or no home visits (n=175). Breastfeeding practices were studied on days 1, 10, 30, 60, 90, 120, 150, and 180 by researchers unaware of group allocation. The primary outcome measure was the rate of exclusive breastfeeding from birth to 6 months. Analyses were by intention to treat.\n The hospital-training intervention achieved a high rate (70%) of exclusive breastfeeding in the hospitals, but this rate was not sustained at home and at 10 days of age only 30% of infants were exclusively breastfed The patterns of exclusive breastfeeding in the two trial groups for days 10-180 differed significantly (p<0.0001), with a mean aggregated prevalence of 45% among the group assigned home visits compared with 13% for the group assigned none.\n The BFHI achieves high rates of exclusive breastfeeding in hospital; however, in Brazil at least, the rates fall rapidly thereafter. Reliance on the BFHI as a strategy for breastfeeding promotion should be reassessed. A combination of promotional systems (hospital-based and in the community) is needed.", "nan", "To investigate whether antenatal breast feeding education alone or postnatal lactation support alone improves rates of exclusive breast feeding compared with routine hospital care.\n Randomised controlled trial.\n A tertiary hospital in Singapore.\n 450 women with uncomplicated pregnancies.\n Primary outcomes were rates of exclusive breast feeding at discharge from hospital and two weeks, six weeks, three months, and six months after delivery. Secondary outcomes were rates of any breast feeding.\n Compared with women who received routine care, women in the postnatal support group were more likely to breastfeed exclusively at two weeks (relative risk 1.82, 95% confidence interval 1.14 to 2.90), six weeks (1.85, 1.11 to 3.09), three months (1.87, 1.03 to 3.41), and six months (2.12, 1.03 to 4.37) postnatally. Women receiving antenatal education were more likely to breast feed exclusively at six weeks (1.73, 1.04 to 2.90), three months (1.92, 1.07 to 3.48), and six months (2.16, 1.05 to 4.43) postnatally. The numbers needed to treat to achieve one woman exclusively breast feeding at six months were 11 (6 to 80) for postnatal support and 10 (6 to 60) for antenatal education. Women who received postnatal support were more likely to exclusively or predominantly breast feed two weeks after delivery compared with women who received antenatal education (1.53, 1.01 to 2.31). The rate of any breastfeeding six weeks after delivery was also higher in the postnatal support group compared with women who received routine care (1.16, 1.02 to 1.31).\n Antenatal breast feeding education and postnatal lactation support, as single interventions based in hospital both significantly improve rates of exclusive breast feeding up to six months after delivery. Postnatal support was marginally more effective than antenatal education.\n Clinical Trials NCT00270920 [ClinicalTrials.gov].", "This randomized clinical trial compared frequencies of exclusive breastfeeding and lactation-related problems during the first 30 days among 74 mothers who received a 30-minute counseling session on breastfeeding technique in the maternity ward, and 137 controls. The frequency of exclusive breastfeeding among mothers who had received intervention was similar to controls by 7 days (79.7% vs 82.5%, respectively) and 30 days (60.8% vs 53.3%). There was no difference between groups in the frequency of sore nipples at 7 and 30 days, in breast engorgement and mastitis, and in the quality of breastfeeding technique at 30 days. Therefore, a single intervention at maternity was not sufficient to improve breastfeeding technique, increase exclusive breastfeeding rates, and reduce the incidence of breastfeeding problems during the first month.", "The purpose of this quasi-experimental study was to test the effects of home visits and telephone contacts on mothers' compliance to breastfeeding in Taiwan. A total of 180 mothers was assigned to three groups: home visit, telephone contact, and control. No significant differences were found between groups. However, multiparas showed a significantly longer duration of breastfeeding and a more positive experience of breastfeeding than primiparas. The best subsets to predict breastfeeding duration were level of breastfeeding easiness and a home visit, which accounted for 20% of the total variance.", "Exclusive breastfeeding (EBF) is reported to be a life-saving intervention in low-income settings. The effect of breastfeeding counselling by peer counsellors was assessed in Africa.\n 24 communities in Burkina Faso, 24 in Uganda, and 34 in South Africa were assigned in a 1:1 ratio, by use of a computer-generated randomisation sequence, to the control or intervention clusters. In the intervention group, we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers. The data gathering team were masked to the intervention allocation. The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks. Country-specific prevalence ratios were adjusted for cluster effects and sites. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00397150.\n 2579 mother-infant pairs were assigned to the intervention or control clusters in Burkina Faso (n=392 and n=402, respectively), Uganda (n=396 and n=369, respectively), and South Africa (n=535 and 485, respectively). The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 (79%) of 392 and 139 (35%) of 402, respectively, in Burkina Faso (prevalence ratio 2·29, 95% CI 1·33-3·92); 323 (82%) of 396 and 161 (44%) of 369, respectively, in Uganda (1·89, 1·70-2·11); and 56 (10%) of 535 and 30 (6%) of 485, respectively, in South Africa (1·72, 1·12-2·63). The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 (77%) and 94 (23%), respectively, in Burkina Faso (3·27, 2·13-5·03); 305 (77%) and 125 (34%), respectively, in Uganda (2·30, 2·00-2·65); and 41 (8%) and 19 (4%), respectively, in South Africa (1·98, 1·30-3·02). At 24 weeks, the prevalences based on 24-h recall were 286 (73%) in the intervention cluster and 88 (22%) in the control cluster in Burkina Faso (3·33, 1·74-6·38); 232 (59%) and 57 (15%), respectively, in Uganda (3·83, 2·97-4·95); and 12 (2%) and two (<1%), respectively, in South Africa (5·70, 1·33-24·26). The prevalences based on 7-day recall were 279 (71%) in the intervention cluster and 38 (9%) in the control cluster in Burkina Faso (7·53, 4·42-12·82); 203 (51%) and 41 (11%), respectively, in Uganda (4·66, 3·35-6·49); and ten (2%) and one (<1%), respectively, in South Africa (9·83, 1·40-69·14). Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 (5%) and 36 (9%), respectively, in Burkina Faso (0·57, 0·27-1·22); 39 (10%) and 32 (9%), respectively, in Uganda (1·13, 0·81-1·59); and 45 (8%) and 33 (7%), respectively, in South Africa (1·16, 0·78-1·75). The prevalence at age 24 weeks in the intervention and control clusters was 26 (7%) and 32 (8%), respectively, in Burkina Faso (0·83, 0·45-1·54); 52 (13%) and 59 (16%), respectively, in Uganda (0·82, 0·58-1·15); and 54 (10%) and 33 (7%), respectively, in South Africa (1·31, 0·89-1·93).\n Low-intensity individual breastfeeding peer counselling is achievable and, although it does not affect the diarrhoea prevalence, can be used to effectively increase EBF prevalence in many sub-Saharan African settings.\n European Union Sixth Framework International Cooperation-Developing Countries, Research Council of Norway, Swedish International Development Cooperation Agency, Norwegian Programme for Development, Research and Education, South African National Research Foundation, and Rockefeller Brothers Foundation.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "Exclusive breastfeeding is recommended worldwide but not commonly practised. We undertook a randomised controlled study of the efficacy of home-based peer counselling to increase the proportion of exclusive breastfeeding among mothers and infants residing in periurban Mexico City.\n Two intervention groups with different counselling frequencies, six visits (44) and three visits (52), were compared with a control group (34) that had no intervention. From March, 1995, to September, 1996, 170 pregnant women were identified by census and invited to participate in the study. Home visits were made during pregnancy and early post partum by peer counsellors recruited from the same community and trained by La Leche League. Data were collected by independent interview. Exclusive breastfeeding was defined by WHO criteria.\n 130 women participated in the study. Only 12 women refused participation. Study groups did not differ in baseline factors. At 3 months post partum, exclusive breastfeeding was practised by 67% of six-visit, 50% of three-visit, and 12% of control mothers (intervention groups vs controls, p<0.001; six-visit vs three-visit, p=0.02). Duration of breastfeeding was significantly (p=0.02) longer in intervention groups than in controls, and fewer intervention than control infants had an episode of diarrhoea (12% vs 26%, p=0.03).\n This is the first reported community-based randomised trial of breastfeeding promotion. Early and repeated contact with peer counsellors was associated with a significant increase in breastfeeding exclusivity and duration. The two-fold decrease in diarrhoea demonstrates the importance of breastfeeding promotion to infant health.", "The purpose of this study was to discover factors related to breastfeeding duration. Of the 131 women who volunteered to complete questionnaires at one, three and six months postpartum, 46 provided baseline data, and 37 and 48 (randomly assigned) constituted low and high intervention groups respectively. Comparisons were made between breastfeeding and bottle feeding. Factors shown at three and six months to be related to duration of breastfeeding at the p < .05 level were: identified high risk factors in labor and delivery, admission of the infant to the intensive care nursery, and length of mother's and/or infant's hospitalization. The three months' data also showed a significant relationship between spontaneous births and `breastfeeding only'. No positive relationship was found between breastfeeding duration and support from nursing staff. The results suggest that when mothers and infants experience intrapartum high risk factors, delivery by cesarean section and long hospital stay, the mothers are likely to stop breastfeeding early.", "We conducted a randomized controlled trial to assess the effectiveness of a support intervention delivered by health professionals to increase the rate and duration of breastfeeding.\n A randomized controlled intervention study was conducted in the period 2000-2001 among 605 mothers who had given birth in a public maternity ward located in the city of Rome, Italy. The intervention consisted of a home visit by a midwife from the maternity ward of the hospital. The outcome of the study was the infant's feeding habits, assessed by a 24-h recall. The effect of the intervention on the duration of breastfeeding was estimated by the Kaplan-Meier method and by the Cox multivariate regression model.\n According to intention-to-treat analysis, there was no significant difference between the intervention and the control group, after controlling for confounding factors (hazard ratio (HR) 1.04; 95% confidence interval (95% CI): 0.85-1.26). The duration of breastfeeding was shorter (HR 1.61; 95% CI: 1.13-2.31) for women in the intervention group who refused the obstetric visit.\n Our study shows that an early home support programme delivered by health professionals was not effective in increasing breastfeeding initiation and duration.", "Women's traditional way of breastfeeding has altered in Jordan with rates declining in recent years.\n The objectives of this study were to test whether the introduction of an educational program supporting breastfeeding would increase the proportion of women who breastfed fully to six months, improve the women's level of breastfeeding knowledge, and decrease the proportion of infants admitted to hospitals due to gastrointestinal illnesses.\n A randomized controlled trial was conducted in 90 primiparous women who had given birth to a healthy, full term, singleton baby at two hospitals in the southern region of Jordan. Women were randomly allocated to either the intervention group (n=45), in which they were offered a one-to-one postnatal educational session and follow-up phone calls at two months and four months postpartum, or the control group (n=45), in which they received routine postnatal care. The primary outcomes were the proportion of women fully breastfeeding their babies at six months and the women's level of breastfeeding knowledge at six months postpartum.\n The postnatal education and support program significantly improved breastfeeding knowledge measured by differences between mean pre- and post-test scores. This was statistically significant for the intervention group (p<0.001) but was not significant for the control (p=0.23). The proportion of women fully breastfeeding their babies at 6 months was not found to be statistically significantly different between the intervention group (39%) and the control group (27%), percentage difference=12% (95% confidence interval [-9% to 30%], Chi squared: χ(2)=3.54, p>0.05).\n Although the postnatal education and support program improved breastfeeding knowledge among women in the study, this increase in knowledge did not translate to an increase in the duration of full breastfeeding to six months.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "To assess the impact of a supportive intervention on the duration of breastfeeding.\n A community based cluster-randomized trial in Western Denmark.\n Fifty-two health visitors and 781 mothers in the intervention group, and 57 health visitors and 816 mothers in the comparison group. Intervention: Health visitors in the intervention group received an 18-h course. The intervention addressed maternal psychosocial factors and consisted of 1-3 home visits during the first 5 weeks post-partum. Health visitors in the comparison group offered their usual practice. Main outcome measure: Duration of exclusive breastfeeding during 6 months of follow-up.\n Mothers in the intervention group had a 14% lower cessation rate (HR = 0.86 CI: 0.75-0.99). Similar results were seen for primipara, and multipara with previously short breastfeeding experience. Mothers in the intervention group received their first home visit earlier, had more visits and practical breastfeeding training within the first 5 weeks. Babies in the intervention group were breastfed more frequently, fewer used pacifiers, and their mothers reported more confidence in not knowing the exact amount of milk their babies had received when being breastfed.\n Home visits in the first 5 weeks following birth may prolong the duration of exclusive breastfeeding. Postnatal support should focus on both psychosocial and practical aspects of breastfeeding. Mothers with no or little previous breastfeeding experience require special attention.", "The goal of this controlled trial was to evaluate the impact of a volunteer telephone support program on the ability of the mothers to reach their breastfeeding objectives and to reduce the number of difficulties while nursing. Two hundred expectant women were randomly assigned to two groups. The first group received the usual services from the professionals and the second had the extra service from a trained volunteer. By comparing the proportions of women still breastfeeding at each month, the present study showed that this type of support was ineffective in meeting the objectives. The gap between the intended length of breastfeeding and the duration achieved was equally large in both groups. Only 30% breastfed for the length of time envisaged during pregnancy. Strategies to increase the effectiveness of this type of service are suggested.", "Exclusive breastfeeding is rare in Bangladesh. About 90% of women have home deliveries, so the Baby-Friendly Hospital Initiative has no mechanism to reach them. Mother support groups do not exist, and community health workers do not have time to promote and support exclusive breastfeeding. To provide this kind of support at the community level, an area in Dhaka was selected for a peer-counseling intervention program. Using certain selection criteria, 1 woman from each community was trained as a peer counselor. The training was based on the World Health Organization/United Nations International Children's Emergency Fund 40-hour breastfeeding counseling course and related books. Counseling skills were taught using demonstrations and role play, followed by practical training in the project area. The intervention was very successful, as 70% of the mothers in the project area breastfed their infants exclusively for 5 months compared to only 6% in the control area. The authors describe the peer counseling training, strategies used for peer counseling visits, and lessons learned.", "Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies. Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries.\n To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants.\n The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted June 1996-December 1997 with a 1-year follow-up.\n Thirty-one maternity hospitals and polyclinics in the Republic of Belarus.\n A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up.\n Sites were randomly assigned to receive an experimental intervention (n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children's Fund, which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support, or a control intervention (n = 15) of continuing usual infant feeding practices and policies.\n Duration of any breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection, 2 or more episodes of respiratory tract infection, and atopic eczema during the first 12 months of life, compared between the intervention and control groups.\n Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69), were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28).\n Our experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life. These results provide a solid scientific underpinning for future interventions to promote breastfeeding.", "To investigate whether offering volunteer support from counsellors in breast feeding would result in more women breast feeding.\n Randomised controlled trial.\n 32 general practices in London and south Essex.\n 720 women considering breast feeding.\n Primary outcome was prevalence of any breast feeding at six weeks. Secondary outcomes were the proportion of women giving any breast feeds, or bottle feeds at four months, duration of any breast feeding, time to introduction of bottle feeds, and satisfaction with breast feeding.\n Offering support in breast feeding did not significantly increase the prevalence of any breast feeding to six weeks (65% (218/336) in the intervention group and 63% (213/336) in the control group; relative risk 1.02, 95% confidence interval 0.84 to 1.24). Survival analysis up to four months confirmed that neither duration of breast feeding nor time to introduction of formula feeds differed significantly between control and intervention groups. Not all women in the intervention group contacted counsellors postnatally, but 73% (123/179) of those who did rated them as very helpful. More women in the intervention group than in the control group said that their most helpful advice came from counsellors rather than from other sources.\n Women valued the support of a counsellor in breast feeding, but the intervention did not significantly increase breastfeeding rates, perhaps because some women did not ask for help.", "To evaluate the effectiveness of home-based peer counselling to increase breastfeeding rates for unfavourably low birthweight babies.\n Randomized clinical trial carried out in maternity hospitals and households in Fortaleza, one of the regions in Brazil with very low income; 1003 mothers and their newborns were selected in eight maternity hospitals. Newborns needed were healthy and weighed less than 3000 g.\n Breastfeeding counselling, conducted by lay counsellors from the community, during home visits carried out on days 5, 15, 30, 60, 90 and 120 after birth.\n Feeding methods in the fourth month of life.\n The intervention increased exclusive breastfeeding (24.7% vs 19.4%; p=0.044), delayed the introduction of formula and increased the time infants substituted breastfeeding to bottle milk (bottle milk 33.4% in the control group and 20.1% in the intervention group; p=0.00002). When comparing the frequency of artificial breastfeeding versus all other forms of breastfeeding (exclusive+predominant+partial), the intervention increased breastfeeding rates in 39% (RR=0.61; CI 95%: 0.50-0.75); 15% of children were free from artificial feeding (absolute risk reduction). The number of families to be visited to avoid one child receiving artificial feeding (NNT) was 7 (CI 95%: 5-13).\n Breastfeeding counselling, promoted by lay counsellors, can impact favourably on exclusive breastfeeding rates and contribute to delaying the utilization of milk formula and weaning. The intervention has great application potential because most cities in the northeast of Brazil count on community health workers that could do the counselling.", "In the Netherlands, the initiation rate of breast-feeding (BF) was 80% in 2002, but only 35% of the mothers continued to breast-feed for 3 months. This study examined the effectiveness of a breast-feeding promotion program to increase the continuation of breast-feeding.\n A cluster-randomized intervention trial was used. Ten child health care centers in three regions of the home health care were randomly allocated to the program or usual care. Elements in the program were health counseling, measures to enhance cooperation, early signaling of breast-feeding problems and continuity of care, and lactation consultancy. Pregnant mothers who applied for home health care in the intervention or usual care regions were enrolled and were followed up from pregnancy until 6 months postpartum (n = 683). The primary outcome measure was the continuation of breast-feeding until at least 3 months.\n The 3-month breast-feeding rate was 32% in the intervention and 38% in the control groups (OR = 0.79, 95% CI = 0.58-1.08).\n The program was not effective. We discuss possible explanations from the design and execution of the trial and give some points for improvement of our program, such as the categories of caregivers involved and the number and duration of contacts after parturition.", "The advantages of breastfeeding have been well established for both mothers and their infants. Existing research reports equivocal effects of early discharge and postpartum home care on breastfeeding success. The purpose of this study was to compare the effects of breastfeeding support offered in hospital and home settings on breastfeeding outcomes and maternal satisfaction for mothers of term and near-term newborns who experienced standard or early discharge.\n In a randomized controlled trial with prognostic stratification for gestational age, 101 term and 37 near-term (35-37 weeks' gestational age) mother-newborn pairs were randomized to either a standard care group (standard care and standard length of hospitalization) or an experimental group (standard hospital care with early discharge and home support from nurses who were certified lactation consultants). Data collection occurred before randomization, at discharge from hospital, and from 5 to 12 days postpartum. Primary outcomes included breastfeeding rates and maternal satisfaction.\n More mothers of term newborns in the experimental group were breastfeeding exclusively at follow-up (p = 0.02) compared with the control group. No significant breastfeeding differences occurred among mothers with near-term newborns in the experimental and standard care groups.\n In-home lactation support appears to facilitate positive breastfeeding outcomes for mothers of term newborns. This may also be a beneficial model of postpartum care for mothers of near-term newborns; however, further research is required. The findings suggest implications for health caregivers and policy makers with respect to postpartum lactation and health care services.", "to evaluate the effects of an extended midwifery support (EMS) programme on the proportion of women who breast feed fully to six months.\n randomised controlled trial.\n large public teaching hospital in Australia.\n 849 women who had given birth to a healthy, term, singleton baby and who wished to breast feed.\n participants were allocated at random to EMS, in which they were offered a one-to-one postnatal educational session and weekly home visits with additional telephone contact by a midwife until their baby was six weeks old; or standard postnatal midwifery support (SMS). Participants were stratified for parity and tertiary education.\n the main outcome measures were prevalence of full and any breast feeding at six months postpartum.\n there was no difference between the groups at six months postpartum for either full breast feeding [EMS 43.3% versus SMS 42.5%, relative risk (RR) 1.02, 95% confidence interval (CI) 0.87-1.19] or any breast feeding (EMS 63.9% versus SMS 67.9%, RR 0.94, 95%CI 0.85-1.04).\n the EMS programme did not succeed in improving breast-feeding rates in a setting where there was high initiation of breast feeding. Breast-feeding rates were high but still fell short of national goals.\n continuing research of programmes designed to promote breast feeding is required in view of the advantages of breast feeding for all mothers and babies.\n Copyright 2008 Elsevier Ltd. All rights reserved.", "To pilot test a newly developed breastfeeding self-efficacy intervention.\n Pilot randomized controlled trial (RCT).\n An acute care hospital located in Northwestern Ontario that is the sole provider of maternity care for the city and referral center for the region.\n One-hundred-and-fifty primiparous women intending to breastfeed their healthy, term, singleton infant.\n A standardized, individualized nursing intervention protocol was designed and administered to increase mothers' breastfeeding self-efficacy. Participants were randomly allocated to the intervention group or control group using sealed, opaque envelopes. Participants in the intervention group received three individualized, self-efficacy enhancing sessions with the researcher: two in-hospital and one by telephone. Participants in the control group received standard in-hospital and community care.\n Feasibility, compliance, and the acceptability of the breastfeeding self-efficacy intervention. Other outcomes assessed were breastfeeding self-efficacy, duration, and exclusivity.\n Findings suggest that the intervention was feasible; there was a high degree of protocol compliance, and the majority of mothers reported that the intervention was beneficial. Mothers in the intervention group had higher rates of breastfeeding self-efficacy, duration, and exclusivity at 4 and 8 weeks postpartum. However, the differences between groups were not statistically significant.\n The pilot RCT provided valuable information in examining the feasibility of the trial design and intervention.\n © 2011 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.", "A randomized intervention trial to promote breast-feeding was carried out in southern Brazil. A group of 450 mothers and babies was visited at home 5, 10 and 20 days after birth and compared to a non-visited control group of the same size. Ninety-two per cent of the families visited received the three home visits planned. The evaluation of breast-feeding patterns and reasons for weaning took place 6 months after birth for both groups. Ninety-four per cent of the group visited and 92% of the non-visited controls group were traced on the occasion of the assessment. The intervention increased the duration of breast-feeding (median duration of 120 days in the group visited and 105 days in the controls; p = 0.03) and delayed the introduction of milk bottles (median age of introduction of 90 days in the group visited and 60 days in the controls; p = 0.01). Causes of weaning were classified as underlying, intermediate and immediate. The most common underlying cause of weaning was \"the baby cried too much\", which suggests that mothers should be taught about normal patterns of infant behaviour in the first weeks of life, particularly the need for crying, and the fact that this not necessarily reflects hunger.", "In a randomised controlled trial a lactation nurse assisted mothers during the early weeks after parturition both in hospital and at home. All mothers who started breast feeding were entered into the trial. The lactation nurse significantly extended duration in the study group compared with controls, particularly during the first four weeks and among women of lower social class.", "A sample of 38 white working class primiparas intending to breast feed were alternately assigned to either an experimental or control group during the last trimester of pregnancy. All women were visited at home antenatally for a structured interview on their attitudes towards and information on breast feeding. The experimental group were visited twice before the birth, seen within the first 5 days in hospital, and visited immediately after they returned home, to enable the provision of information, advice and support regarding breast feeding. All women were seen again at 3 months postpartum. There was a significant difference between the two groups in level of breast feeding success, and explanations for this effect are put forward in terms of the experimental intervention components.", "To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives.\n Randomised controlled trial with six month follow up.\n Recruitment in a university teaching hospital and care provided in women's homes.\n 623 postnatal women allocated at random to intervention (311) or control (312) group. Intervention: Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker. Main outcome measure: General health status as measured by the SF-36 and risk of postnatal depression. Breast feeding rates, satisfaction with care, use of services, and personal costs.\n At six weeks there was no significant improvement in health status among the women in the intervention group. At six weeks the mean total NHS costs were pound 635 for the intervention group and pound 456 for the control group (P=0.001). At six months figures were pound 815 and pound 639 (P=0.001). There were no differences between the groups in use of social services or personal costs. The women in the intervention group were very satisfied with the support worker visits.\n There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36. There were no savings to the NHS over six months after the introduction of the community postnatal support worker service.", "To evaluate the relative effects introducing motivational videotapes and/or peer counseling in Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinics serving African-American women have on breast-feeding duration.\n Experimental intervention study. Pregnant women were enrolled at or before 24 weeks gestation and were followed up until postpartum week 16. Women were interviewed at enrollment, 7 to 10 days, 8 weeks, and 16 weeks postpartum. SUNJECTS/SETTING: One hundred fifteen African-American WIC participants who initiated breast-feeding and who had been enrolled in 1 of 4 clinics.\n Two-by-two factorial design, in which 4 clinics were randomly assigned to receive either no intervention, a motivational video package intervention, a peer-counseling intervention, or both interventions.\n Breast-feeding duration in weeks and relative risk ratios for breast-feeding cessation before 16 weeks postpartum.\n Contingency table analysis, including chi2 tests and log-rank tests; multivariate analysis using Cox proportional hazards regression analysis.\n A higher proportion of women were breast-feeding at 8 and 16 weeks postpartum in the intervention clinics than in the control clinic. The proportion of women reporting breast-feeding declined at 8 and 16 weeks postpartum, but the rate of decline was slower in the 3 intervention clinics than in the control clinic. Being younger than 19 years of age or older than 25 years of age, having a male infant, and returning to work or school all negatively affected breastfeeding duration, whereas previous breast-feeding experience positively influenced breast-feeding duration.\n WIC-based peer counselor support and motivational videos can positively affect the duration of breast-feeding among African-American women. WIC nutritionists and other health professionals in contact with this population should expand their efforts toward promoting increased duration of breast-feeding.", "To study the factors involved in the maintenance of exclusive breastfeeding in healthy infants during the first 4 months of life, with emphasis on the role of pediatricians. Material and methods: A longitudinal study was carried out with 101 healthy term babies at a pediatrics outpatient clinic in Uberaba, state of Minas Gerais, Brazil. The babies were divided at random into three groups: G1, receiving advice from a multiprofessional breastfeeding team; G2, receiving advice from a pediatrician trained in breastfeeding; and G3, receiving advice from a pediatrician with no breastfeeding training. Group randomization was confirmed by analysis of variance. The factors involved in the type of feeding at 4 months were analyzed by the chi-square test, by analysis of variance and by multiple variable analysis.\n At the end of follow-up, Groups 1 and 2 showed similar percentages with respect to exclusive breastfeeding. In addition, the percentage of exclusively breastfed babies in Groups 1 and 2 was significantly higher than in Group 3 (p = 0.002). The use of a pacifier was negatively correlated with exclusive breastfeeding (p = 0.003). More maternal schooling increased the chance of exclusive breastfeeding at 4 months (p = 0.041).\n In this study, a pediatrician who was prepared and motivated to encourage breastfeeding performed similarly to a multiprofessional breastfeeding team in terms of promoting exclusive breastfeeding until 4 months.", "Teenage pregnancies are associated with negative socioeconomic effects. Our aim was to ascertain whether a postnatal home-visiting service for teenage mothers younger than age 18 years could reduce the frequency of adverse neonatal outcomes and improve knowledge of contraception, breastfeeding, and infant vaccination schedules in this parent group.\n We enrolled 139 adolescents, attending a teenage pregnancy clinic, in a randomised controlled trial. After completing an antenatal questionnaire designed to assess their knowledge of contraception, infant vaccination, and breastfeeding, we assigned participants to either receive five structured postnatal home visits by nurse-midwives (n=65) or not (n=71). Assessment interviews were done 6 months postpartum. Our primary endpoint was unadjusted difference in knowledge between groups, and incidence of predefined adverse neonatal outcomes. Analysis was by intention to treat.\n Three women withdrew before randomisation because of late fetal loss, 11 mothers withdrew because of adverse neonatal outcomes (adverse neonatal outcome was a primary endpoint, but resulted in withdrawal from the study for knowledge outcomes), and one left voluntarily. Follow-up data were, therefore, available for 124 teenagers. Postnatal home visits were associated with a reduction in adverse neonatal outcomes (intervention: 2; control: 9; relative risk 0.24, 95% CI 0.05-1.08), and a significant increase in contraception knowledge (mean difference 0.92, 95% CI 0.32-1.52). However, there was no significant increase in knowledge with respect to breastfeeding or infant vaccination schedules associated with the home visits.\n Postnatal home-visiting services by nurse-midwives reduce adverse neonatal events and improve contraception outcomes, but do not affect breastfeeding or infant vaccination knowledge or compliance.", "A prospective study of the course of breast feeding was carried out in 75 randomly selected women. Weekly interviews were performed from the day after delivery until the termination of breast feeding, but in no case for longer than 6 months. In each case a detailed analysis was made of the factors leading to transient lactation crises or to complete cessation of breast feeding. A second group of 71 mothers, also randomly selected, was interviewed in retrospect only, 6 months after delivery, and served as controls. Twenty-four weeks after delivery 47% of the mothers in the weekly interview group were still breast feeding. The corresponding figure in the control group was 38%. In both groups only few mothers terminated lactation for medical reasons, while about one fourth stopped for some other reason and about one half because of a combination of factors. Brief case reports are presented to illustrate how varying the factors were that threatened breast feeding.", "Breastfeeding can ameliorate some of the complex health issues faced by low-income families. Women who breastfeed and their infants have lower health care costs compared with those who formula feed. Increasing the duration of breastfeeding is recognized as a national priority, particularly for low-income women. This community-based randomized clinical trial involving low-income mothers compared usual care with an intervention comprising hospital and home visits, and telephone support by a community health nurse/peer counselor team for 6 months after delivery.\n Forty-one women were recruited after delivery of a full-term singleton infant and randomly assigned to intervention or usual care groups.\n Women receiving the community health intervention breastfed longer than the women receiving usual care. The infants in the intervention group had fewer sick visits and reported use of fewer medications than infants in the usual care group. The intervention cost ($301/mother) was partially offset by cost savings on formula and health care.\n Community health nurse and peer counselor support can increase breastfeeding duration in low-income women, and has the potential to reduce total costs including the cost of support.", "To evaluate the effectiveness of a breastfeeding promotion program in the Women, Infant and Children (WIC) Supplemental Nutrition Program participants.\n This randomized clinical trial included 52 women in the intervention group who received one-to-one pre- and postnatal breastfeeding education and support from a lactation consultant. Women (n = 52) randomized to controls received standard breastfeeding services. Data regarding their infants' feeding (classified as exclusive, partial, and bottle) during the first 7 days, 1, 2, and 3 months of age were compared. Additionally, the mothers were surveyed to assess their knowledge, attitude, and beliefs regarding breastfeeding.\n Among the 104 enrolled women, 91 (87.5%) were Hispanic. Almost all the pregnant women had planned to breastfeed their infants. Although the majority of women reported breastfeeding their infants, 45.6% in the intervention group and 28.9% of controls practiced exclusive breastfeeding during the first 7 days. By 3 months, the rate of exclusive breastfeeding in the intervention and control groups had dropped to 13.9% and 10.5%, respectively. Parity, mode of delivery, previous experience with breastfeeding, rooming in, and return to work did not significantly affect the exclusive breastfeeding rate. Maternal knowledge, attitude, and beliefs regarding breastfeeding were comparable between the study groups at the baseline stage as well as 3 months postpartum.\n Participation in the proposed breastfeeding promotion program by the low-income mothers was associated with an insignificant increase in the exclusive breastfeeding rate during the first 3 postpartum months.", "Exclusive breastfeeding is recommended until age 6 months. We assessed the feasibility, effectiveness, and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India.\n We developed the intervention through formative research, pair-matched eight communities on their baseline characteristics, and randomised one of each pair to receive the intervention and the other to no specific intervention. We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities. We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities. Feeding at age 3 months, and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed. All analyses were by intention to treat.\n We assessed 483 and 412 individuals at 3 months in the intervention and control groups, respectively, and 468 and 412 at 6 months. At 3 months, exclusive breastfeeding rates were 79% (381) in the intervention and 48% (197) in the control communities (odds ratio 4.02, 95% CI 3.01-5.38, p<0.0001). The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months (0.64, 0.44-0.95, p=0.028) and 6 months (0.85, 0.72-0.99, p=0.04). The mean weights and lengths, and the proportion with weight-for-height or height-for-age Z scores of 2 or less, at age 3 months and 6 months did not differ much between groups. Intervention effect on exclusive breastfeeding, diarrhoeal morbidity, and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births.\n Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering.", "Recognizing that an expectant father may influence a mother's decision to breast- or formula-feed, we tested the effectiveness of a simple, educational intervention that was designed to encourage fathers to advocate for breastfeeding and to assist his partner if she chooses to breastfeed.\n We conducted a randomized controlled trial in which expectant fathers (n = 59) were assigned randomly to attend either a 2-hour intervention class on infant care and breastfeeding promotion (intervention) or a class on infant care only (control group). The classes, which were led by a peer-educator, were interactive and informal and utilized different media to create an accessible environment for participants. Couples were recruited during the second trimester from a university obstetrics practice.\n Overall, breastfeeding was initiated by 74% of women whose partners attended the intervention class, as compared with 41% of women whose partners attended the control class (P = .02).\n Expectant fathers can be influential advocates for breastfeeding, playing a critical role in encouraging a woman to breastfeed her newborn infant.", "To determine whether an individualized, prenatal and postnatal, lactation consultant intervention resulted in increased cumulative intensity of breastfeeding up to 52 weeks.\n The randomized, nonblinded, controlled trial recruited women from prenatal care. Baseline prenatal interviews covered demographic data and breastfeeding experience, intention, and knowledge. Interviews at 1, 2, 3, 4, 6, 8, 10, and 12 months after birth collected data on weekly feeding patterns, infant illness, and infant health care use.\n Two community health centers serving low-income, primarily Hispanic and/or black women.\n The analytic sample included 304 women (intervention: n = 145; control: n = 159) with > or = 1 postnatal interview.\n Study lactation consultants attempted 2 prenatal meetings, a postpartum hospital visit, and/or home visits and telephone calls. Control subjects received the standard of care.\n Cumulative breastfeeding intensity at 13 and 52 weeks, based on self-reports of weekly feeding, on a 7-level scale.\n The intervention group was more likely to breastfeed through week 20 (53.0% vs 39.3%). Exclusive breastfeeding rates were low and did not differ according to group. In multivariate analyses, control subjects had lower breastfeeding intensity at 13 weeks (odds ratio [OR]: 1.90; 95% confidence interval [CI]: 1.13-3.20) and 52 weeks (OR: 2.50; 95% CI: 1.48-4.21). US-born control subjects had lowest breastfeeding intensity at 13 weeks (OR: 5.22; 95% CI: 2.43-11.22) and 52 weeks (OR: 5.25; 95% CI: 2.44-11.29). There were no significant differences in breastfeeding intensity among the US-born intervention, foreign-born intervention, and foreign-born control groups.\n This \"best-practices\" intervention was effective in increasing breastfeeding duration and intensity. Breastfeeding promotion should focus on US-born women and exclusive breastfeeding.", "Harmful effects of short postpartum hospital stays include dehydration and malnutrition of breastfed infants. These may be prevented by adequate breastfeeding frequency; however, rigorous research to determine the relative effectiveness of various follow-up strategies in supporting breastfeeding frequency is absent. This study addressed the question, \"Is there a difference in breastfeeding frequency or infant weight gain for singleton infants discharged within 36 hours' postpartum who received either community nurse (home visit) or hospital nurse (clinic) follow-up?\"\n A randomized, controlled trial was conducted at a university teaching hospital (3700 births/y) and affiliated community health centers. A consecutive sample of 586 healthy mother-infant pairs were recruited from January 1997 to September 1998 before discharge; 513 (87.5%) contributed data on 1 or more outcomes. Forty-eight-hour postpartum telephone contact and day 3 nurse contact in the home (experimental) or at the hospital (control) were provided. The main outcomes measured were breastfeeding frequency and infant weight gain assessed at 2 weeks' postpartum by maternal diary and weight at home by research assistants, masked to group allocation.\n No clinically important or statistically significant group differences were found in daily breastfeeding frequency (mean difference experimental minus control = 0.1 feeds [95% confidence interval: -0.1-0.3]) or daily rate of infant weight gain (-1.1 g [-2.5-0.3]) based on intention-to-treat analyses.\n Follow-up by nurses after short postpartum hospital stays, in either the home or a hospital-based clinic, of healthy infants discharged at <36 hours seems associated with satisfactory infant breastfeeding outcomes.", "Social support has been shown to be greatly important for breastfeeding success. The objective of this study was to investigate if mothers who were attended by midwives and nurses specially trained in breastfeeding counseling perceived better continuity of care and emotional and informative breastfeeding support than mothers who received only routine care.\n Ten municipalities, each with an antenatal center and child health center, in southwest Sweden were randomized either to intervention or control municipalities. The intervention included a process-oriented training in breastfeeding counseling and continuity of care at the antenatal and child health centers. Primiparas were asked to evaluate the care given, and those living in the control municipalities were divided into control groups A and B. Data collection took place at different points in time for the two control groups. The 540 mothers responded to 3 questionnaires at 3 days and at 3 and 9 months postpartum. The perception of support provided by the health professionals and from the family classes was rated on Likert scales.\n Intervention group mothers rated the breastfeeding information given during the family class as significantly better during pregnancy than both control groups, and better than control group B mothers at 3 months postpartum; compared with both control groups, intervention group mothers perceived that they received significantly better overall support and that postnatal nurses provided better information about breastfeeding and the baby's needs. At 9 months, intervention group mothers were more satisfied with knowledge about social rights, information about the baby's needs, and their social network than control group B mothers. Both intervention group and control group B mothers perceived better overall support than control group A during pregnancy. At 3 and 9 months, intervention group mothers perceived that postnatal nurses were more sensitive and understanding compared with both control groups.\n After implementation of a process-oriented breastfeeding training program for antenatal midwives and postnatal nurses that included an intervention guaranteeing continuity of care, the mothers were more satisfied with emotional and informative support during the first 9 months postpartum. The results lend support to family classes incorporating continuity of care.", "The main aim of the study was to discover if a midwife home visiting programme has a significant effect on the prevalence of health problems and breast feeding behaviour of mothers who delivered normally and their healthy fullterm newborn babies, during a period of 42 days after delivery. Another aim was to compare the mothers', the midwife's, and the doctor's findings of prevalence of health problems at the end of the puerperium period.\n A randomised controlled trial was carried out. One group of mothers and their infants were randomly allocated to a home visiting group (Group A); the other group (Group B) was only visited at day 42.\n The study was carried out at the University Teaching Hospital (UTH) in Lusaka, the capital city of Zambia.\n A total of 408 mothers who had a normal delivery and gave birth to a healthy fullterm infant, as assessed by the attending midwife, were randomised to two groups. Group A consisted of 208 mother/infant dyads who were visited by a midwife in their homes at days 3, 7, 28, and 42 after delivery and Group B consisted of 200 mother/infant dyads who were only visited at day 42.\n At day 42 an equal proportion (30%) of mothers in both groups perceived that they had health problems. The prevalence of infant health problems in Group B was significantly higher (p < 0.01) as perceived by mothers. There were more mothers in Group B (p < 0.01) perceiving insufficient milk production and giving supplementary feeding. At day 42, mothers in Group A (56%) took more actions than mothers in Group B (41%) to solve infant health problems (p < 0.03). In both groups the mothers' perceived own health problems, were significantly higher (p < 0.01) than those observed by the obstetrician and those observed by the midwife. The midwife found more infant health problems in Group B (p < 0.01) than in Group A and more infants with health problems in both groups compared with the paediatrician's findings (p < 0.01).\n There was a significant difference between the mothers' reported health problems and the health problems identified by the midwife and the doctors. The study shows that a midwife home visit and individual health education to mothers, reduce the prevalence of infant health problems, and enables the mother to more often take action when an infant health problem is identified. There is a need to re-evaluate the midwifery training curriculums with the intention to include more infant management care.", "A trial was conducted with 51 women randomly assigned either to a conventional nursing care group or to an individualized professional support group to examine the effect of professional support on breastfeeding status at 4 weeks postpartum. All participants identified themselves as having no prior support. At 4 weeks postpartum, 17 out of 25 (68%) and 26 out of 26 (100%) women in the control and intervention groups, respectively, continued to breastfeed (P = .005). Results indicate that postpartum care augmented with individualized professional support commenced in the hospital and continued in the community significantly increases the duration of breastfeeding among women who identify themselves as being without support for the first month postpartum.", "Exclusive breast-feeding (EBF) rates remain low despite numerous health benefits associated with this behavior. We conducted a randomized trial on the effect of lactation counseling on EBF, which controlled for the Hawthorne effect while also varying the timing of the intervention. Pregnant women attending prenatal clinics in Tema were randomly assigned to 1 of 2 intervention groups (IG) or to a control group (C), as follows: 1) EBF support given pre-, peri-, and postnatally (IG1; n = 43); 2) EBF support given only peri- and postnatally (IG2; n = 44); or 3) nonbreast-feeding health educational support (C; n = 49) that had an equal amount of contact with lactation counselors. Two educational sessions were provided prenatally, and 9 home follow-up visits were provided in the 6-mo postpartum period. Infant feeding data were collected monthly at the participant's home. The 3 groups did not differ in sociodemographic characteristics. At 6 mo postpartum, 90.0% in IG1 and 74.4% in IG2 had exclusively breast-fed during the previous month. By contrast, only 47.7% in C were doing so (P = 0.008). Similarly, the percentage of EBF during the 6 mo was significantly higher (P = 0.02) among IG1 and IG2 (39.5%) than among C (19.6%). The 100% increase in EBF rates can be attributed to the lactation counseling provided. Additional prenatal EBF support may not be needed within a context of strong routine prenatal EBF education.", "This quasi-experimental study was conducted in Shiraz, the Islamic Republic of Iran, on 120 pairs of mothers and infants in a maternity hospital that had a rooming-in programme. All 59 mothers in the study group received breastfeeding education, face-to-face, after delivery and during follow-up for 4 months in the mother and child health (MCH) centre or in their homes; the remaining 61 mothers comprised the control group. Exclusive breastfeeding rates were significantly higher in the study group (54%) than in the control group (6.5%), but 5% and 18% of infants, respectively, in the study and control groups had stopped breastfeeding by the age of 4 months. The mean number of days of diarrhoea experienced by infants in the study group were significantly lower (P < or = 0.004) than in the control group. At the end of 4 months, the mean weight and length of the infants were significantly higher (both P < 0.05) in the study group than in the control group. The findings indicate that rooming-in is very important for promoting exclusive breastfeeding and that there is a need for continuous breastfeeding education of mothers.", "Despite growing evidence of the benefits of prolonged breastfeeding for mother and infant health, the rate of breastfeeding at infant age of 6 months remains below the Healthy People 2010 goal. The greatest decrease in the breastfeeding rate occurs during the first 4 postpartum weeks. Mothers who discontinue breastfeeding early are more likely to report lack of confidence in their ability to breastfeed, problems with the infant latching or suckling, and lack of individualized encouragement from their clinicians in the early postdischarge period. Observational studies suggest that primary care physicians can increase breastfeeding rates through specific advice and practices during routine preventive visits. However, robust scientific evidence based on randomized, controlled trials is currently lacking.\n The purpose of this study was to determine whether attending an early, routine, preventive, outpatient visit delivered in a primary care physician's office would improve breastfeeding outcomes.\n The study was a prospective, randomized, parallel-group, open trial.\n Participants were recruited at a level 3 maternity facility, with an average of 2000 births per year, in France.\n A total of 231 mothers who had delivered a healthy singleton infant (gestational age: > or =37 completed weeks) and were breastfeeding on the day of discharge were recruited and randomized (116 were assigned to the intervention group and 115 to the control group) between October 1, 2001, and May 31, 2002; 226 mother-infant pairs (112 in the intervention group and 114 in the control group) contributed data on outcomes.\n Support for breastfeeding in the control group included the usual verbal encouragement provided by the maternity ward staff members, a general health assessment and an evaluation for evidence of successful breastfeeding behavior by the pediatrician working in the obstetrics department on the day of discharge, provision of the telephone number of a peer support group, mandatory routine, preventive, outpatient visits at 1, 2, 3, 4, 5, and 6 months of infant age, and 10 weeks of paid maternity leave (extended to 18 weeks after the birth of the third child). In addition to the usual predischarge and postdischarge support, the mothers in the intervention group were invited to attend an individual, routine, preventive, outpatient visit in the office of 1 of the 17 participating primary care physicians (pediatricians or family physicians) within 2 weeks after the birth. The participating physicians received a 5-hour training program on breastfeeding, delivered in 2 parts in 1 month, before the beginning of the study.\n The primary outcome was the prevalence of exclusive breastfeeding reported at 4 weeks (defined as giving maternal milk as the only food source, with no other foods or liquids, other than vitamins or medications, being given). The secondary outcomes included any breastfeeding reported at 4 weeks, breastfeeding duration, breastfeeding difficulties, and satisfaction with breastfeeding experiences. Classification into breastfeeding categories reported at 4 weeks was based on 24-hour dietary recall.\n Ninety-two mothers (79.3%) assigned to the intervention group and 8 mothers (7.0%) assigned to the control group reported that they had attended the routine, preventive, outpatient visit in the office of 1 of the 17 primary care physicians participating in the study. Mothers in the intervention group were more likely to report exclusive breastfeeding at 4 weeks (83.9% vs 71.9%; hazard ratio: 1.17; 95% confidence interval [CI]: 1.01-1.34) and longer breastfeeding duration (median: 18 weeks vs 13 weeks; hazard ratio: 1.40; 95% CI: 1.03-1.92). They were less likely to report any breastfeeding difficulties (55.3% vs 72.8%; hazard ratio: 0.76; 95% CI: 0.62-0.93). There was no significant difference between the 2 groups with respect to the rate of any breastfeeding at 4 weeks (89.3% vs 81.6%; hazard ratio: 1.09; 95% CI: 0.98-1.22) and the rate of mothers fairly or very satisfied with their breastfeeding experiences (91.1% vs 87.7%; hazard ratio: 1.04; 95% CI: 0.95-1.14).\n Although we cannot exclude the possibility that findings might differ in other health care systems, this study provides preliminary evidence of the efficacy of breastfeeding support through an early, routine, preventive visit in the offices of trained primary care physicians. Our findings also suggest that a short training program for practicing physicians might contribute to improving breastfeeding outcomes. Multifaceted interventions aiming to support breastfeeding should involve primary care physicians.", "A randomized controlled trial is used to determine whether assigning mixed feeders to a breastfeeding clinic within 1 week postpartum will increase exclusive breastfeeding at 1 month among Hispanic immigrants. Subjects are eligible for the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), and 85% are monolingual Hispanic. Mothers (n = 522) of infants at low risk for hyperbilirubinemia are approached at bedside 20 to 48 hours after delivery and randomly assigned to treatment or control groups. Intent-to-treat analysis of feeding behavior at 4 weeks postpartum indicates that the intervention group is more likely to be exclusively breastfeeding (16.4% vs 10% in the control group, P = .03; adjusted odds ratio 1.87; 95% confidence interval, 1.07-3.26); that the incidence of formula supplementation does not differ between groups; and that the intervention group is less likely to supplement with water and tea (P < .002).", "The importance of exclusive breast-feeding in the first 6 mo of life is widely recognized, but most mothers still do not reach this goal. Several studies have shown that face-to-face lactation counseling is effective in increasing not only exclusive breast-feeding rates but also the total duration of breast-feeding. However, it is unclear whether counseling could increase breast milk intake. The purpose of this study was to evaluate the effect of lactation counseling on breast milk intake, assessed through the deuterium dilution method. This was a blind, randomized intervention trial of lactation counseling in a sample of 188 babies born in Pelotas, selected with the same criteria used for the WHO Multicentre Growth Reference Study (MGRS). The main outcomes were breast-feeding pattern and duration for all infants as well as breast milk intake for a subsample of 68 infants at the age of 4 mo. Mothers in the control group were almost twice as likely to stop breast-feeding by 4 mo as those in the intervention group (prevalence ratio 1.85; P = 0.04). Cox regression confirmed that the velocity of weaning was twice as high in the control group. Breast milk and total water intakes did not differ between the groups. The deuterium dilution technique proved to be a practical means of assessing breast milk intake. Lactation counseling reduced early weaning, but breast milk intake at 4 mo was not affected.", "The authors analyzed data from a trial assessing the efficacy of breastfeeding peer counseling (PC) for increasing exclusive breastfeeding (EBF) to (1) examine whether different ethnic groups responded differently to the intervention and (2) document the determinants of EBF. At 2 months postpartum, the prevalence of EBF in the intervention group was 11.4% among Puerto Ricans compared to 44.4% among non-Puerto Ricans (P = .008). Multivariate logistic regression analyses showed that women who had the intention prenatally to engage in EBF were more likely to do so and those whose mothers lived in the United States were less likely to engage in EBF at hospital discharge. At 2 months postpartum, mothers who were breastfed as children were more likely to engage in EBF, whereas non-Puerto Ricans had a significantly greater response to the intervention than Puerto Ricans (odds ratio, 6.40; 95% confidence interval, 1.45-28.33). There is a need for further studies to determine why different ethnic groups respond differently to EBF promotion interventions.", "Food preferences are established in early childhood and track later in life. Therefore, it is important to promote healthy feeding practices as early as possible. A randomized field trial was conducted with 500 mother-child pairs from a low-income area of São Leopoldo, State of Rio Grande do Sul, Brazil, to evaluate the impact of a nutritional intervention in the first year of life on the dietary quality of 3- to 4-y-old children. Mother-child pairs were randomized either to intervention and control groups and dietary counseling was provided for mothers in the intervention group during 10 home visits in the course of the first year of life. These visits were carried out by fieldworkers who counseled the mothers about the Ten Steps for Healthy Feeding from Birth to Two Years of Age, based on the WHO guidelines. Dietary intake was assessed at 3-4 y of age for 345 children using two 24-h food recalls. Overall diet quality was determined by the Healthy Eating Index. The prevalence of poor diet in the intervention group was lower compared with the control group [relative risk (RR) = 0.30; 95% CI = 0.13-0.71). The number of children who achieved the 75th percentile for the vegetable and fruit component score was higher in the intervention than in control group (RR = 1.95; 95% CI = 1.31-2.89 and RR = 1.49; 95% CI = 1.07-2.07, respectively). Such data provide evidence that dietary counseling for mothers during the first year of life improves the overall dietary quality of children in a low-income population.", "We investigated the effectiveness of a program of intensive postpartum support for low-income, breast-feeding women and identified potential predictors of prolonged breast-feeding in this population. Ninety-seven low-income women were randomized to receive intensive postpartum education and support for breast-feeding or to receive only the routine assistance provided by the obstetrical nurses. Both groups were telephoned 6 weeks post partum to determine the method of infant feeding then, and those still breast-feeding were contacted monthly until complete weaning had occurred. No significant difference in breast-feeding duration between the two groups was noted. There was no association between duration of nursing and race, marital status, or the need to return to work or school. Earlier age at introduction of supplement, younger maternal age, and participation in prenatal classes predicted breast-feeding duration by logistic regression.", "To assess the clinical effectiveness and cost effectiveness of a policy to provide breastfeeding groups for pregnant and breastfeeding women.\n Cluster randomised controlled trial with prospective mixed method embedded case studies to evaluate implementation processes.\n Primary care in Scotland.\n Pregnant women, breastfeeding mothers, and babies registered with 14 of 66 eligible clusters of general practices (localities) in Scotland that routinely collect breastfeeding outcome data.\n Localities set up new breastfeeding groups to provide population coverage; control localities did not change group activity.\n Primary outcome: any breast feeding at 6-8 weeks from routinely collected data for two pre-trial years and two trial years. Secondary outcomes: any breast feeding at birth, 5-7 days, and 8-9 months; maternal satisfaction.\n Between 1 February 2005 and 31 January 2007, 9747 birth records existed for intervention localities and 9111 for control localities. The number of breastfeeding groups increased from 10 to 27 in intervention localities, where 1310 women attended, and remained at 10 groups in control localities. No significant differences in breastfeeding outcomes were found. Any breast feeding at 6-8 weeks declined from 27% to 26% in intervention localities and increased from 29% to 30% in control localities (P=0.08, adjusted for pre-trial rate). Any breast feeding at 6-8 weeks increased from 38% to 39% in localities not participating in the trial. Women who attended breastfeeding groups were older (P<0.001) than women initiating breast feeding who did not attend and had higher income (P=0.02) than women in the control localities who attended postnatal groups. The locality cost was pound13 400 (euro14 410; $20 144) a year.\n A policy for providing breastfeeding groups in relatively deprived areas of Scotland did not improve breastfeeding rates at 6-8 weeks. The costs of running groups would be similar to the costs of visiting women at home.\n Current Controlled Trials ISRCTN44857041.", "The aim of this study was to determine the effects of breastfeeding education/support offered at home on day 3 postpartum on breastfeeding duration and knowledge.\n The study included a total of 60 women who gave birth at Zübeyde Hanım Maternity Hospital located in Aydın, Turkey. In addition to a standard breastfeeding education in the first few hours after delivery, which was provided to all women in this \"baby-friendly initiative\" (BFI) hospital, the mothers in the intervention group received breastfeeding education at home on day 3 postpartum from supporters.\n Both groups were comparable in terms of maternal and neonatal characteristics. The breastfeeding education/support offered during a home visit on day 3 postpartum was associated with a significant increase in the percentage of exclusively breastfed infants both at 2 weeks and 6 weeks, and at 6 months, and was also associated with a significant increase in exclusive breastfeeding and in total breastfeeding duration. In addition, increased breastfeeding knowledge scores were observed in the intervention group at 2 weeks and at 6 weeks after delivery, when compared with the respective scores in the control group.\n Breastfeeding education offered at home on day 3 postpartum was effective in increasing the breastfeeding duration and breastfeeding knowledge.", "Early postpartum home visiting is universal in many Western countries. Studies from developing countries on the effects of home visits are rare. In Syria, where the postpartum period is rather ignored, this study aimed to assess whether a community-based intervention of postnatal home visits has an effect on maternal postpartum morbidities; infant morbidity; uptake of postpartum care; use of contraceptive methods; and on selected neonatal health practices.\n A randomized controlled trial was carried out in Damascus. Three groups of new mothers were randomly allocated to receive either 4 postnatal home visits (A), one visit (B), or no visit (C).\n A total of 876 women were allocated and followed up.\n Registered midwives with special training made a one or a series of home visits providing information, educating, and supporting women.\n A significantly higher proportion of mothers in Groups A and B reported exclusively breastfeeding their infants (28.5% and 30%, respectively) as compared with Group C (20%), who received no visits. There were no reported differences between groups in other outcomes.\n While postpartum home visits significantly increased exclusive breastfeeding, other outcomes did not change. Further studies framed in a nonbiomedical context are needed. Other innovative approaches to improve postnatal care in Syria are needed.", "The purpose of this study was to assess whether providing a breastfeeding support team results in higher breastfeeding rates at 6, 12, and 24 weeks postpartum among urban low-income mothers.\n Design: A randomized controlled trial with mother-infant dyads recruited from 2 urban hospitals. Participants: Breastfeeding mothers of full-term infants who were eligible for Special Supplemental Nutrition Program for Women, Infants, and Children (n=328) were randomized to intervention (n=168) or usual-care group (n=160). Intervention: The 24-week intervention included hospital visits by a breastfeeding support team, home visits, telephone support, and 24-hour pager access. The usual-care group received standard care. Outcome Measure: Breastfeeding status was assessed by self-report at 6, 12, and 24 weeks postpartum.\n There were no differences in the sociodemographic characteristics between the groups: 87% were African American, 80% single, and 51% primiparous. Compared with the usual-care group, more women reported breastfeeding in the intervention at 6 weeks postpartum, 66.7% vs 56.9% (odds ratio, 1.71; 95% confidence interval, 1.07-2.76). The difference in rates at 12 weeks postpartum, 49.4% vs 40.6%, and 24 weeks postpartum, 29.2% vs 28.1%, were not statistically significant.\n The intervention group was more likely to be breastfeeding at 6 weeks postpartum compared with the usual-care group, a time that coincided with the most intensive part of the intervention.\n 2010 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.", "Most mothers stop breast-feeding before the recommended 6 months post partum. A systematic review showed that breast-feeding support programs by health care professionals did not substantially improve breast-feeding outcomes beyond 2 months post partum. We conducted a randomized controlled trial to evaluate the effect of peer (mother-to-mother) support on breast-feeding duration among first-time breast-feeding mothers.\n We recruited 256 breast-feeding mothers from 2 semi-urban community hospitals near Toronto and randomly assigned them to a control group (conventional care) or a peer support group (conventional care plus telephone-based support, initiated within 48 hours after hospital discharge, from a woman experienced with breast-feeding who attended a 2.5-hour orientation session). Follow-up of breast-feeding duration, maternal satisfaction with infant feeding method and perceptions of peer support received was conducted at 4, 8 and 12 weeks post partum.\n Significantly more mothers in the peer support group than in the control group continued to breast-feed at 3 months post partum (81.1% v. 66.9%, p = 0.01) and did so exclusively (56.8% v. 40.3%, p = 0.01). Breast-feeding rates at 4, 8 and 12 weeks post partum were 92.4%, 84.8% and 81.1% respectively among the mothers in the peer support group, as compared with 83.9%, 75.0% and 66.9% among those in the control group (p < or = 0.05 for all time periods). The corresponding relative risks were 1.10 (95% confidence interval [CI] 1.01-2.72) at 4 weeks, 1.13 (95% CI 1.00-1.28) at 8 weeks and 1.21 (95% CI 1.04-1.41) at 12 weeks post partum. In addition, when asked for an overall rating of their feeding experience, significantly fewer mothers in the peer support group than in the control group were dissatisfied (1.5% v. 10.5%) (p = 0.02). Of the 130 mothers who evaluated the peer support intervention, 81.6% were satisfied with their peer volunteer experience and 100% felt that all new breast-feeding mothers should be offered this peer support intervention.\n The telephone-based peer support intervention was effective in maintaining breast-feeding to 3 months post partum and improving satisfaction with the infant feeding experience. The high satisfaction with and acceptance of the intervention indicates that breast-feeding peer support programs, in conjunction with professional health services, are effective." ]

[ "2262233", "2937252", "1458806", "3516907", "8294170", "16223204", "2076622", "2040104", "15155436", "12472980", "2105985", "10568212", "16078335", "11926695", "15722295", "2696550", "1810522", "7804585", "2530027", "12866363", "3913078", "7541355", "2202553", "7021266", "338395" ]

[ "Topical indomethacin in overuse injuries in athletes. A randomized double-blind study comparing Elmetacin with oral indomethacin and placebo.", "[Local anti-inflammatory treatment with a ketoprofen gel: current clinical findings].", "[Efficacy and tolerability of ketoprofen lysine salt foam for topical use in the treatment of traumatic pathologies of the locomotor apparatus].", "Portable thermogram technique for topically applied benzydamine cream in acute soft-tissue injuries.", "Ketoprofen 2.5% gel versus placebo gel in the treatment of acute soft tissue injuries.", "Analgesic efficacy of a lecithin-vehiculated diclofenac epolamine gel in shoulder periarthritis and lateral epicondylitis: a placebo-controlled, multicenter, randomized, double-blind clinical trial.", "A double-blind comparison of naproxen gel and placebo in the treatment of soft tissue injuries.", "Piroxicam 0.5% topical gel compared to placebo in the treatment of acute soft tissue injuries: a double-blind study comparing efficacy and safety.", "Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study.", "Comparative efficacy of a proprietary topical ibuprofen gel and oral ibuprofen in acute soft tissue injuries: a randomized, double-blind study.", "A double-blind study of the efficacy of topical ketorolac tromethamine gel in the treatment of ankle sprain, in comparison to placebo and etofenamate.", "Double-blind controlled clinical study of the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel compared with diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel in patients with peri and extraarticular inflammatory diseases.", "Topical ketoprofen patch in the treatment of tendinitis: a randomized, double blind, placebo controlled study.", "Efficacy of a proprietary ibuprofen gel in soft tissue injuries: a randomised, double-blind, placebo-controlled study.", "Topical ketoprofen patch (100 mg) for the treatment of ankle sprain: a randomized, double-blind, placebo-controlled study.", "Soft tissue trauma: a randomised controlled trial of the topical application of felbinac, a new NSAID.", "Effects of meclofenamic acid in the treatment of lesions deriving from minor traumatology.", "Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains.", "[Treatment of soft tissue trauma with BPAA gel. Results of an Italian multicenter study vs. placebo].", "Double-blind, randomized, controlled study on the efficacy and safety of a novel diclofenac epolamine gel formulated with lecithin for the treatment of sprains, strains and contusions.", "[Treatment of sprained ankles with 5% benzydamine creme. A double-blind study].", "Flurbiprofen local action transcutaneous (LAT): clinical evaluation in the treatment of acute ankle sprains.", "Clinical evaluation of niflumic acid gel in the treatment of uncomplicated ankle sprains.", "Controlled clinical trial with Fentiazac cream in sport microtraumatology.", "A double-blind clinical study with benzydamine 3% cream on soft tissue injuries in an occupational health centre." ]

[ "In this double-blind trial in 70 athletes with superficial overuse injuries, the effect of topically and systemically administered indomethacin was compared with a placebo control. The treatment period was 2 weeks and blindness was secured by the double-dummy technique. The basic data of the patients showed no significant differences on entry to the study. The majority of cases were acute or subacute, the mean duration of symptoms being 7.4 weeks. The results showed a marked therapeutic effect after 3-7 days of treatment and statistically significant differences between the topical formulation and the placebo were reached in the parameters patients assessment of improvement and pain in connection with daily activity within the first week of treatment. However, during the second week the statistical significances were lost. Only in the topically treated patients local adverse reactions were observed. In the oral indomethacin group all reactions were systemic, GI- and CNS-complaints being predominant. The results on efficacy as well as adverse reactions favour the use of topical indomethacin in superficial overuse injuries in athletes.", "nan", "In this study the authors evaluated the efficacy and tolerability of a foam of 15% ketoprofen lysine salt versus placebo in patients with articular traumas, pains and strains, distortions etc. All parameters considered were statistically significantly decreased after 7 days of active treatment as compared to placebo. Pain score decreased significantly at pressure (p < 0.001), pain on active movement (p < 0.005), pain on passive movement and pain at rest. Efficacy of the active foam was graded as satisfactory in 81.7% and its tolerability in 92.7% versus 44% and 29% with placebo respectively. Patients reported high acceptability (89%) of the new foam formulation. No systemic or local side effects were observed or reported. The 15% ketoprofen lysine salt foam for topical use can be considered an effective antiinflammatory and analgesic drug for the treatment of minor orthopedic and traumatic disorders, and was found to be perfectly tolerated.", "A double-blind, parallel trial was undertaken with 3% benzydamine cream compared with a matching placebo, on patients suffering acute soft-tissue injuries. 21 patients received active material and 22 received placebo material. Patients applied the cream lightly 6 times a day for 6 days. Assessments were made (by the same physician) on days 0, 2, 4 and 6, and signs and symptoms were graded as \"absent\", \"slight\", \"moderate\" or \"severe\". Thermograms were taken on day 0 and day 6. The results showed significant relief of spontaneous pain, significant reduction in tenderness on pressure and in swelling on days 2, 4 and 6 of the trial, and a significant reduction in functional impairment on days 4 and 6, in the patients who had received the 3% benzydamine cream.", "A parallel, double-blind, placebo controlled and randomized study in a single center was done with ketoprofen 2.5% gel to treat acute soft tissue injuries. Patients applied the gel twice a day for seven days, corresponding to 250 mg of ketoprofen per day. Assessments were made on the third and seventh day by VAS, subjective evaluation and pain threshold algometry. The study group consisted of 29 patients and the control group 27 patients. Pain at rest was significantly relieved in the ketoprofen group, whereas in the placebo group the difference was not significant. In terms of side-effects, no difference between the groups was noticed. In both groups, local dermal irritation was found. Our results suggested that ketoprofen 2.5% gel was safe and superior to placebo in the treatment of soft tissue injuries.", "Diclofenac epolamine (2-hydroxyethyl-pyrrolidine) (DHEP) is a diclofenac salt endowed with enhanced cutaneous permeation. To optimize its absorption after topical application, a lecithin-enriched DHEP 1.3% gel has been developed (DHEP lecithin gel) and investigated in patients with shoulder periarthritis and lateral epicondylitis in a placebo-controlled, multicenter double-blind clinical trial. One hundred fifty-eight patients were randomized to a 10-day treatment with DHEP lecithin gel or placebo (5 g t.i.d. applied on the painful area). The efficacy criteria were pain measured by visual analog scale (VAS) while performing a specific standardized movement, intake of rescue medication (paracetamol), and the disabilities of the arm, shoulder and hand (DASH) questionnaire. VAS scores indicated a consistently higher analgesic activity of DHEP lecithin gel. At day 3, pain was reduced by -20.1 +/- 20.2 and -9.9 +/- 12.7 mm in the DHEP lecithin gel- and placebo-treated patients, respectively (p < 0.001); at day 6 of treatment, DHEP lecithin gel induced a pain reduction of -33.2 +/- 26.1 mm, while the reduction achieved with placebo was only -21.2 +/- 18.8 mm (p < 0.001). The mean changes in DASH questionnaire indicated that DHEP lecithin gel was more effective than placebo in improving patient well-being and reducing difficulties in performing the activities most severely impaired by rheumatism, while no difference was observed between the two treatments in consumption of rescue medication. In conclusion, these results indicate that DHEP lecithin gel is a topically effective analgesic product in patients with shoulder periarthritis or lateral epicondylitis and provide further evidence on the use of topical nonsteroidal anti-inflammatory drugs as an optimal approach to the treatment of localized musculoskeletal disorders.", "A double-blind study was carried out in 120 patients who had received soft tissue injuries within the preceding 48 hours to compare the effectiveness of naproxen gel (10%) with placebo gel (base alone). The injuries were predominantly synovitis and tendinitis. Standard clinical evaluations of the patients' condition were made by physicians and patients on entry and after 3 and 7 days of treatment. Both treatments resulted in a significant improvement in symptoms, but naproxen gel was significantly superior to placebo gel (p less than 0.05). The response produced by naproxen was more rapid; all symptoms were significantly improved by Day 3 (p less than 0.05). The greater efficacy of naproxen was reflected in a lower usage of active drug compared with placebo which was consistent throughout the study. While the physicians' global assessments of the two gels did not differ significantly, the patients showed a preference in favour of naproxen (p less than 0.05) Naproxen gel was well tolerated; only 1 adverse event of itching occurred. It is suggested that naproxen gel offers an effective and convenient alternative to systemic non-steroidal anti-inflammatory drugs for patients where side-effects are to be avoided or when oral administration is undesirable.", "Piroxicam 0.5% gel, administered as 5 mg q.i.d. was compared to placebo gel in a double-blind study of the treatment of selected acute soft tissue injuries (ankle or acromioclavicular sprains, supraspinatus, or achilles tendinitis). A total of 200 patients (100 per treatment) were evaluated. Six patients (6%) in the piroxicam group discontinued treatment due to inefficacy, compared to 42/100 in the placebo group (p less than 0.001). Significantly greater reduction in pain (spontaneous and on movement), degree of joint restriction, pressure threshold and tenderness of the affected site were observed with piroxicam gel compared to placebo gel. The time to improvement was significantly less with the piroxicam gel. The overall evaluation of efficacy and of benefit to injury favoured piroxicam over placebo (p less than 0.0001). Both piroxicam and placebo gels were well tolerated, with 7 piroxicam and 15 placebo patients reporting primarily skin-related adverse effects. This study indicates that piroxicam 0.5% gel, administered as 5 mg q.i.d. is an effective treatment of musculoskeletal injuries (sprains and tendinitis), is significantly more effective than placebo, and is well tolerated.", "To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries.\n This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrollment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient.\n The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group.\n A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries.", "The efficacy of a novel, proprietary topical formulation of ibuprofen 5% gel (Ibugel) and ibuprofen 400 mg tablets (1200 mg daily) was compared in a double-blind, double-dummy, parallel group study in patients with acute soft tissue injuries. Patients received either active gel plus placebo tablets (n = 50) or active tablets plus placebo gel (n = 50) for at least 7 days. The gel was applied and one tablet was taken three times daily. The two treatments showed similar efficacy. There were no significant differences between the groups for either the primary efficacy endpoint, the median time for the injury to be rated as 'completely better' by the patients (>14 days active gel, 13.5 days active tablets; P = 0.59), or for other efficacy measures including the times to clinically significant relief from pain at rest or on movement and swelling. In summary, ibuprofen gel shows similar efficacy to oral ibuprofen 400 mg and may offer improved tolerability.", "In a double-blind, placebo-controlled study the efficacy and safety of topical ketorolac tromethamine were assessed in the reduction of inflammation and pain due to ankle sprain. Ketorolac 2% gel was compared with etofenamate and placebo (ketorolac vehicle) in a 15-day study. Patients attended for visits on days 1 (admission), 2, 3, 4, 8, and 15 of the study. Measurements of efficacy were ankle volume, pain measured on visual analogue scales (VAS) and verbal rating of pain. Safety was assessed by volunteered adverse events and vital signs. A total of 37 patients was admitted to the study of whom 13 received ketorolac, 12 placebo, and 12 etofenamate. One patient receiving ketorolac was lost to follow-up on day 15 owing to an unrelated accident. The remaining 36 patients completed the study. Ketorolac was significantly better than placebo in reducing the volume of the injured ankle based on the maximum, the area under the curve, and the day 15 percentage changes in ankle volume. Results for etofenamate were similar to those for ketorolac for all three variables and there were no significant differences between the active treatments. Reductions in VAS pain at rest were more marked in the ketorolac group than either of the other groups at all visits. On day 4 the differences between ketorolac and each of the other groups were statistically significant. Reductions in VAS pain on movement were also greatest for the ketorolac group at all visits. The differences between ketorolac and each of the other groups achieved statistical significance on days 4 and 8, but were marginal in terms of significance on day 2.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the efficacy and tolerability of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel (DHEP lecithin gel, with 1.3% DHEP and 2.4% lecithin) compared with the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel (DHEP gel) in peri and extraarticular inflammatory states, a controlled, randomized, double-blind clinical study was conducted. Two groups of 50 patients each were enrolled and were given one of the two different formulations with a slight massage on the painful area three times a day for 10 consecutive days. Patients received a self-evaluation notebook in which to record daily assessment of spontaneous pain (Huskisson's visual analogue scale). On days 0, 3 and 10, the patients were visited by the investigator. All patients completed the study. The assessment of spontaneous pain showed that although pain decreased in both groups, the decrease was more marked in patients taking DEHP lecithin gel and that it reached a statistically significant difference at days 5, 6, 7 and 8. This decrease was also confirmed by assessments on the ordinal scale. Although periarticular swelling disappeared in both groups, swelling severity decreased sooner in patients taking DHEP lecithin gel. The efficacy and safety of both treatments was judged to be good or excellent by 70% of the patients in each group. The efficacy of the active principle, pyrrolidine salt, is confirmed. Moreover, the formulation containing lecithin passes through the skin lipid barrier more easily than the formulation without lecithin and is as valid as the other in the therapy of rheumatic disorders. Finally, DHEP lecithin gel preparation has a quicker therapeutic action on symptoms, such as spontaneous pain and local swelling, than DHEP gel.", "To evaluate the efficacy and tolerability of ketoprofen patch in the treatment of tendinitis.\n A multicenter, 14 day, randomized, double blind placebo controlled trial of a once-a-day ketoprofen 100 mg patch in symptomatic tendinitis of recent onset, not requiring orthopedic or surgical treatment. Pain on daily activities scored on a 100 mm visual analog scale was the primary efficacy criterion. Other criteria were spontaneous pain at rest, pain on full passive motion, pain relief, and pain intensity assessed twice daily by the patient (calculation of total pain relief and summed time-weighted pain intensity difference). Statistical analysis was performed on the differences between the 2 groups in the intention-to-treat population.\n One hundred seventy-two patients were included. Good compliance was obtained in 98% of patients. Twenty-six patients (15%) discontinued the study mainly because of adverse events, inefficacy, or cure. Decrease in pain after one week of treatment (primary criterion) was -38.4 +/- 25.6 mm (56%) and -25.8 +/- 24.5 mm (37%) in the ketoprofen and placebo groups, respectively (p = 0.0013). The differences of the secondary criteria during the trial between the 2 groups were significant more often than not. Tolerance was considered satisfactory in both groups, most adverse events reported being local reactions: 47 versus 44 were possibly or probably related to treatment in the ketoprofen and placebo groups, respectively. These local skin reactions resolved spontaneously and rarely led to premature termination of treatment.\n This trial suggested that a 3-14 day course of treatment by ketoprofen patch is useful in nonarticular rheumatisms, the duration of treatment depending on the results obtained. The safety profile revealed no unexpected adverse events.", "The efficacy of a novel, proprietary topical formulation of ibuprofen 5% gel (Ibugel) was evaluated in a placebo-controlled study in patients with soft tissue injuries. Patients received either active gel (n=40) or placebo gel (n=41) for a maximum of seven days. Pain and interference with physical activity were assessed daily using visual analogue scales. There was a significant difference (p<0.001) in favour of active treatment for the time to achieve clinically meaningful reduction in pain. By day 7, 75% of patients in the active gel group had a clinically meaningful reduction of pain compared with 39% of patients who received placebo. Despite differences between study centres, the data for interference with physical activity also showed an advantage for active treatment. By day 7, 79% of patients in the active gel group had a clinically meaningful reduction in interference with physical activity, compared with 44% of patients who received placebo.", "Topical nonsteroidal anti-inflammatory drugs offer the advantage of enhanced drug delivery to local affected tissues with low plasma levels and an expected reduced incidence of systemic adverse events (mainly peptic ulcer disease and gastrointestinal hemorrhage).\n To test the efficacy and tolerability of a 100-mg patch of ketoprofen applied once a day.\n Randomized controlled clinical trial; Level of evidence, 1.\n The 2-week trial included patients suffering painful (spontaneous pain >or=50 mm on a 0- to 100-mm visual analog scale), benign (grade I or II), recent (<2 days) ankle sprains as a model of general traumatic soft tissue injuries. The primary efficacy criterion was spontaneous pain change after 7 days of treatment in the intention-to-treat population. One hundred sixty-three patients were randomized (ketoprofen, 81; placebo, 82).\n After 1 week of treatment, the decrease in spontaneous pain was -50+/-20 mm for ketoprofen and -38+/-24 mm for the placebo, showing a statistically significant intergroup difference (P=.0007). The majority of the secondary criteria were also statistically significant in favor of the ketoprofen patch. Tolerance was good in both groups, adverse events being mostly local.\n This trial suggested that a 7-day course of treatment with a ketoprofen patch is useful in benign ankle sprain, without revealing unexpected adverse events.", "Two hundred and thirty-one patients with acute soft tissue injuries were treated in a double-blind placebo-controlled study of felbinac (biphenylacetic acid) gel applied three times daily to the injured site. Those treated with felbinac had significantly greater improvement at Day 4 (p less than 0.001) and Day 7 (p less than 0.02) than those who received placebo. Patients' self-assessment diary cards confirmed superiority of the active treatment as early as Day 2 of the study. Local skin reactions were few (three per cent), mild and recovered spontaneously. Felbinac is an effective management for acute soft tissue injuries and because of its topical application may be safer than oral non-steroidal anti-inflammatory drugs for the treatment of these conditions.", "The clinical efficacy and tolerability of topical 5% meclofenamic acid gel versus placebo and oral sodium meclofenamate versus sodium naproxen were evaluated in patients affected with minor traumatologies. Ninety patients were studied: 60 were treated with either meclofenamic acid gel or placebo for 10 days, and 30 were administered with either sodium meclofenamate capsules or sodium naproxen capsules for 7 days. The 5% meclofenamic acid gel and its sodium salt in capsules proved significantly more rapid and efficient than did the reference compounds in reducing pain symptomatology. In the patients treated with 5% meclofenamic acid gel, a greater effect was seen as regards rapidity of spontaneous movement and nocturnal pain reduction. In other variables examined, that is, surface and deep hyperalgesia, and swelling and functional restriction, there was also a significantly higher efficacy than with placebo. Confirmation of the therapeutic efficacy of meclofenamic acid (sodium salt) was obtained with the capsule formulation, that was seen to exert a significant analgesic and antiphlogistic action; the onset of this action was particularly rapid. Both formulations of meclofenamic acid (gel and capsules) were found to be well tolerated. Thus, in the examined formulations, meclofenamic acid proved to be a useful tool in the treatment of lesions in the minor traumatology category.", "One hundred patients who presented to the accident and emergency (A&E) department with an acute ankle sprain were entered into a study to determine the efficacy of topical ibuprofen cream by using a double-blind placebo controlled design in a single type of soft-tissue injury. The subjects were given either topical ibuprofen cream or a placebo cream in addition to the standard management of the department. Patients kept diaries recording walking ability and pain visual analogue scales for resting, standing and walking. A total of 51 patients returned diaries that were suitable for analysis. Patients using the topical ibuprofen cream had significant reduction in pain scores over the first 48 h of treatment.", "A double-blind study vs placebo was carried out on 82 pts suffering from soft tissue trauma, to evaluate the efficacy and tolerance of a new anti-inflammatory, non-steroidal analgesic for topical use, 3% BPAA. Clinical results obtained by the group treated with BPAA gel were highly significant (p = 0.01) and positive, showing absence of local and systemic side-effects. Accordingly, BPAA gel can be recommended for treatment of soft tissue trauma.", "To evaluate the efficacy of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel formulated with lecithin (DHEP lecithin) compared with diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel (DHEP gel) without lecithin in mild-to-moderate posttraumatic injuries (grade 1 ankle, knee and muscle injuries), a multicenter, double-blind, controlled study was carried out. A total of 100 patients were enrolled and randomly assigned to either DHEP lecithin (n = 52) or DHEP gel (n = 48) treatment. All patients concluded the treatment period except for five, who did not turn up to their respective investigational sites for the follow-up visits. According to an intention-to-treat approach, they were all included in the statistical analysis. As for the efficacy and safety analysis, the primary variable was \"pain on movement\" as measured by a Huskisson visual analog scale. During the first 3 days of treatment each group recorded a significant within-group decrease, but patients treated with DHEP lecithin showed a decrease in absolute value that was statistically greater than that obtained with DHEP gel (p = 0.025). At the end of the treatment period (day 10) the difference between groups was still statistically significant (p = 0.036). The statistical analysis of the secondary efficacy variables showed significant results in favor of DHEP lecithin treatment. These were superimposable on the results found for the primary variable. The global efficacy and tolerability judgments, reported either by patient or by physician, showed no statistical difference between treatment groups. Due to the presence of lecithin in the new gel formulation, DHEP lecithin showed a faster and significantly more marked therapeutic effect compared with that of DHEP gel.", "nan", "One hundred and thirty-one male and female outpatients, aged 18-70 yr, with acute pain in the ankle joint caused by a post-traumatic sprain, entered a multicentre, randomised, double-blind, parallel-group, study. The patients were assigned to a 40 mg flurbiprofen patch (n = 65) or a non-medicated (but otherwise identical) control (n = 66), 12-hourly over 7 days, and were assessed at entry and after 3 and 7 days treatment. On day 7, spontaneous pain (the prime efficacy parameter), as evaluated by the patient on a visual analogue scale in the physician's office, showed significant improvement in the 40 mg flurbiprofen patch group compared to control (change from baseline) (p = 0.039), a result corroborated by the evaluation of the periarticular oedema: a reduction of 77.4% was observed in the 40 mg flurbiprofen patch group, compared with 63.8% in the control group (p = 0.025). The other selected efficacy criteria showed changes with a trend in favour of the 40 mg flurbiprofen patch but without statistical significance. Two mild and local adverse events were reported by two flurbiprofen patch patients, but neither patients discontinued the treatment prematurely. Physicians and patients found the flurbiprofen patch to be efficacious and well tolerated. Compliance was excellent in both groups. The efficacy and tolerability of the 40 mg flurbiprofen patch are therefore confirmed in the treatment of acute ankle sprains.", "A double-blind, placebo-controlled, multi-centre study was carried out to assess the efficacy and tolerability of percutaneous niflumic acid gel in the treatment of uncomplicated ankle sprains. Sixty patients were enrolled in three centres and were randomly allocated to receive treatment with 2.5% percutaneous niflumic acid gel or placebo gel applied 3-times daily for 7 days. Clinical evaluations were made on entry to the study, after 3 days and at the end of treatment. The major efficacy criteria were the pain felt by the patient and the investigators' and patients' global evaluation of effectiveness of the treatment. Adverse events that occurred were also noted. The results showed that topically applied 2.5% niflumic acid gel was superior to placebo in the treatment of ankle sprains in respect of all major parameters studied. Niflumic acid gel and the placebo were shown to be equally well tolerated. The study findings indicate that treatment with topical niflumic acid gel is effective in treating uncomplicated ankle sprains and results in improved clinical signs on Day 4 and after 7 days.", "Fentiazac 5% cream was applied topically on limited articular and extra-articular inflammatory lesions in the course of a double-blind clinical trial versus placebo. The drug proved to be satisfactorily tolerated and also therapeutically effective since it changed significantly (p less than 0.05--less than 0.01) the spontaneous course of the microtraumatic pathologic pattern producing an early attenuation and resolution of the painful and functional symptomatic pattern.", "A double-blind, controlled clinical study with benzydamine hydrochloride 3% cream was conducted in an Occupational Health Centre on fifty patients with soft tissue injuries (two mild, ten moderate and thirteen severe cases in the placebo group and one mild, thirteen moderate and twelve severe cases in the active group). The trial demonstrated the significant therapeutic superiority of 3% benzydamine cream over inactive placebo in all six qualitative parameters for traumatic inflammatory changes at the end of a six-day assessment and a marked improvement of symptoms event two days after the onset of therapy. In addition, tbe incidental use of ultrasound therapy together with the standard treatment revealed the value of the active drug as an effective couplant. Neither group suffered any side-effects. Although the size of population studied was small, it was apparent that active treatment with benzydamine was a distinct aid to healing of soft tissue injuries and this should be confirmed with further large-scale clinical trials." ]

[ "12625668", "2446054", "10464004", "9692411", "6387888", "3904322", "2242456", "6872291", "2874067", "2021561", "440653", "3142396", "1415419", "2183619", "8058230", "7573260", "2883043", "7428566", "6131164", "4174507", "2180474", "1477017", "7757311", "1398694", "3056503", "6407638" ]

[ "Methyldopa versus no drug treatment in the management of mild pre-eclampsia.", "Ketanserin versus alpha-methyldopa in the treatment of hypertension during pregnancy: a preliminary report.", "24-hour ambulatory blood pressure monitoring: a comparison between transdermal glyceryl-trinitrate and oral nifedipine.", "Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. Gruppo di Studio Ipertensione in Gravidanza.", "A placebo controlled trial of metoprolol in the treatment of hypertension in pregnancy.", "A prospective controlled trial of metoprolol-hydralazine treatment in hypertension during pregnancy.", "Atenolol in essential hypertension during pregnancy.", "Propranolol in pregnancy three year prospective study.", "Management of pregnancy-induced hypertension with pindolol--comparative study with methyldopa.", "The prevention of the maternal manifestations of pre-eclampsia by intensive antihypertensive treatment.", "Antihypertensive treatment and pregnancy outcome in patients with mild chronic hypertension.", "[Randomized, comparative study on the treatment of moderate arterial hypertension during pregnancy: methyldopa, acebutolol, labetalol].", "A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term.", "A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy.", "Nicardipine versus metoprolol in the treatment of hypertension during pregnancy: a randomized comparative trial.", "Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy: a randomized placebo-controlled study.", "Treatment of hypertension in pregnancy with methyldopa: a randomized double blind study.", "Comparison of the alpha and beta blocking drug, labetalol, and methyl dopa in the treatment of moderate and severe pregnancy-induced hypertension.", "Placebo-controlled trial of atenolol in treatment of pregnancy-associated hypertension.", "A controlled trial of hypotensive agents in hypertension in pregnancy.", "A randomized comparison of early with conservative use of antihypertensive drugs in the management of pregnancy-induced hypertension.", "A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension.", "Beta-adrenergic blocking agents in the treatment of pregnancy-induced hypertension.", "A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension.", "Comparison of antihypertensive efficacy and perinatal safety of labetalol and methyldopa in the treatment of hypertension in pregnancy: a randomized controlled trial.", "Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy." ]

[ "To evaluate the efficacy of methyldopa in the treatment of mild pre-eclampsia, to prevent its progress and to investigate its effect on the pregnancy outcomes.\n Randomised clinical trial.\n Wad Medani Hospital in the central Sudan.\n Seventy primigravidae with single, alive baby of 28-36 weeks gestational age suffering from true mild pre-eclampsia were enrolled. The patients were randomised in two groups, treatment group who received methyldopa 750-4000 mg/day (n=34) and a control group who received no treatment (n=36). All the (treatment and control) patients were drug followed as in-patients till the delivery, seen with their babies on the days 7, 42 after the delivery.\n The outcomes examined were, rise of the diastolic blood pressure to 110 mm Hg or more, occurrence of imminent eclampsia or the eclampsia, if the maturity could be achieved, occurrence of intrauterine growth retardation, abruptio placentae, mode of delivery, birth weight, placental weight, perinatal death, Apgar score and referral of the babies to the pediatrician.\n Three out of 34 (8.8%) of the treatment group had a rise in the diastolic blood pressure of 110 mm Hg, 18/36 (50%) of the control had a rise in the diastolic blood pressure of 110 mmHg (p < 0.05). Three out of thirty four (8.8%) of the treatment group developed imminent eclampsia, while 10/36 (27.8) of the control group developed imminent eclampsia (p < 0.05). The maturity was achieved in 82.3% and 88.8% of the treatment and the control, respectively (p > 0.05). There were ten (14.2%) perinatal deaths, four of them in the treatment group, while six in the control (p > 0.05). There was no difference regarding birth weight, occurrence of intrauterine growth retardation, placental weight, mode of delivery, Apgar score, referral of the babies to the paediatrician. No patient developed eclampsia or abruptio placenta; there was no maternal death in both groups.\n Methyldopa can prevent the progress of the mild pre-eclampsia to severe pre-eclampsia, without affecting the maturity, birthweight or the neonatal outcomes.", "The antihypertensive efficacy of acute treatment with the serotonin receptor antagonist, ketanserin, in women with preeclampsia has been recently documented. The purpose of this study was to determine the safety and efficacy of chronic ketanserin treatment in a group of 20 hypertensive pregnant women: 10 received daily oral doses of ketanserin (20-80 mg), and 10 were treated with oral alpha-methyldopa (500-2000 mg). This study includes (a) patients with a sustained elevation of systolic blood pressure higher than 159 mm Hg and/or diastolic blood pressure higher than 99 mm Hg at bed rest, and (b) hypertensive patients with systolic blood pressure higher than 140 mm Hg or diastolic blood pressure higher than 90 mm Hg with superimposed symptoms such as headaches, stomach aches, and neurological disturbances. A significant and comparable decrease in blood pressure was noted in both groups, in relation with pretreatment levels; no adverse affects were observed in mother or fetus from the ketanserin and alpha-methyldopa groups.", "The objective of the present study is to compare the effectiveness of transdermal glyceryl-trinitrate versus oral nifedipine in lowering blood pressure in patients affected by pregnancy-induced hypertension (PIH). Thirty-six consecutive pregnant women have been evaluated at different gestational ages after the diagnosis of PIH or preeclampsia (PE). After a 24-h ambulatory blood pressure monitoring, patients were allocated to three groups: those receiving oral nifedipine and those receiving transdermal glyceryl-trinitrate in a continuous (24 h/day) or intermittent (16 h/day) administration. A second blood pressure monitoring was performed after 2 weeks of treatment. Systolic and diastolic blood pressure were compared by using the Cosinor method looking at mesor, amplitude, and acrophase. Baseline systolic and diastolic blood pressure was similar among the three groups. Neither the transdermal glyceryl-trinitrate administered for 24 or 16 h nor oral nifedipine affected systolic and diastolic blood pressure. Analysis of variance showed that the posttreatment values were similar among the groups. Further studies are needed to verify the possible use of transdermal glyceryl-trinitrate as an antihypertensive drug during pregnancy.", "To compare the effect of routine treatment with the calcium channel blocker nifedipine in mild to moderate hypertension in pregnancy.\n Randomised clinical trial.\n General and University hospitals.\n Pregnant women, between 12 and 34 weeks of gestation, with chronic, pregnancy-induced or unclassifiable hypertension and diastolic pressure between 90 and 110 mmHg.\n Eligible women were randomly assigned treatment with slow-release nifedipine, 10 mg twice daily until delivery, or no treatment. In the no treatment group nifedipine was given if the diastolic pressure exceeded 110 mmHg. A total of 145 women were assigned nifedipine and 138 no treatment.\n In the nifedipine group 45.0% of women were delivered before term, compared with 37.0% in the no treatment group; the difference was not significant. In all, 56.3% of women allocated nifedipine and 62.1% allocated no treatment underwent caesarean section; the difference was not statistically different (OR 0.7, 95% CI 0.4-1.1). There was no significant difference between the two groups in the percentage of babies weighing less than the 10th centile (OR 0.8; 95% CI 0.4-1.4) or in the mean birthweight. The frequency of admission of infants to the neonatal intensive care unit was not affected by treatment.\n This trial found no benefit on pregnancy outcome of routine treatment with nifedipine. In clinical practice, the treatment of hypertension in pregnancy may be delayed until the hypertension becomes severe.", "nan", "In an open, controlled trial, treatment with a combination of metoprolol and hydralazine was compared with non-pharmacological management of mild and moderate hypertension in pregnancy. One hundred and sixty-one women participated in the study. The drug-treated group showed significantly better blood pressure control than the group not given antihypertensives. Induction of labor before term, because of maternal or fetal complications, was somewhat more frequent in the control group. Nine women in the treatment group and 5 in the control group developed albuminuria. Three infants in the drug-treated group died perinatally, and one in the control group. The outcome for the newborns was similar in both groups concerning birth weight, head circumference and Apgar score and in the frequencies of respiratory distress, bradycardia and hypoglycemia. The better blood pressure control achieved with these drugs makes it possible to treat the patient at home and reduce the risk of emergency delivery, but treatment does not seem to be mandatory for a good outcome of the pregnancy in cases of mild and moderate hypertension during pregnancy.", "To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension.\n Prospective, randomised, double blind, placebo controlled study.\n Hospital clinic.\n 33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks.\n Blood pressure and birth weight.\n 14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached.\n The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g).\n Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.", "We compared propranolol with methyldopa in a randomized prospective study of 28 women with pregnancy associated hypertension. Both drugs were equally effective in controlling maternal hypertension. There was no significant difference in the birthweights of the babies in each group. However one infant born to a mother receiving propranolol had symptomatic hypoglycaemia. The mean peak levels of propranolol, propranolol glucuronide, 4-hydroxypropranolol, and 4-hydroxypropranolol glucuronide were not significantly different in the first, second, third trimesters and at least 3 months post partum. The mean peak plasma level of naphthoxylactic acid however was significantly less in the third trimester compared with post partum levels. Propranolol and its metabolites were found to cross into breast milk with the maximum dose likely to be ingested by the infant as either propranolol or propranolol glucuronide being 7 micrograms of propranolol per 100 g of breast milk, being approximately 0.1% of the maternal dose.", "Thirty-two consecutive women with pregnancy-induced hypertension of early onset were randomly allocated to treatment with pindolol or methyldopa. There was no difference between the groups in regard to the average time of delivery (36.33 vs. 36.6 weeks) and weight of the newborn (2850 vs. 2870 g). A significant drop in systolic (P less than 0.005) and diastolic (P less than 0.05) blood pressure was observed in the group of patients treated with pindolol as compared with the methyldopa group. In the pindolol group an improvement in renal function was observed as determined by CCT and serum creatinine. There were no side effects from the drugs in the mother or in the newborn.", "The purpose of the study was to determine if reduction of pregnancy hypertension to normal prevented the clinical maternal manifestations of pre-eclampsia. Thirty-six women with hypertension, but without proteinuria, were allotted at random to a test group of 17 who received intensive treatment, and a control group of 19 who were managed according to routine methods by hospital staff unconnected with the study. The development of proteinuria was chosen as an indicator of pre-eclampsia. Proteinuria developed significantly more often in the control group (in six of the 19 women) than in the test group (in one of the 17 women).", "nan", "The aim of this prospective, monocentric, opened study and with random order for antihypertensive sequence was to compare a betablocker with sympathomimetic activity (ACE) and an alphabetablocker (LAB) to the gold standard treatment (MD) in moderate HDP (BP greater than 90 mmHg). This study (January 1984 to December 1985) includes 63 women, mean age 28.2 years, divided into three comparable subgroups (age, parity, risk factors and initial level of SBP/DBP). Initial doses are 500 mg/bid (MD), and 400 mg/bid (ACE, LAB) and optimal dosages could not be respectively more than 1500 mg/bid (MD) or 1200 mg/bid (ACE, LAB). Usual criteria for maternal and foetal care are taken into account. The chi 2 test, the Student \"t\" test and the Kruskall Wallis test were used for statistical analysis. The results show: 1--A similar antihypertensive effect for MD and LAB, but significantly less for ACE (initial PAD-37th week PAD: MD +/- 18.8 +/- 2; LAB = -17.9 +/- 3; ACE = - 8.2 +/- 2.7 mmHg, p less than 0.02; 2--A more frequent adjustment of daily dosage with MD (n = 15) than with ACE (n = 10) or LAB (n = 7); 3--The absence of any significant difference for uricemia level, platelet counts, foetal cardiac rythm, and occurrence of pre-eclampsia (MD = 4; ACE = 3; LAB = 4; 4--An equivalent birth-weight (MD = 3110 +/- 628 g; ACE = 3115 +/- 645.(ABSTRACT TRUNCATED AT 250 WORDS)", "The objective of our study was to test the hypothesis that treatment with nifedipine for mild preeclampsia remote from term reduces the number of days of maternal hospitalization and improves pregnancy outcome.\n A total of 200 patients at 26 to 36 weeks' gestation were randomly allocated to treatment with either bed rest alone (n = 100) or bed rest in combination with nifedipine (n = 100).\n Patients receiving nifedipine had significantly lower systolic (p < 0.0001) and diastolic (p < 0.0001) blood pressures during therapy. Severe hypertension as an indication for delivery was significantly (p < 0.05) more frequent in the bed-rest-alone group. The two study groups had similar average days of maternal hospitalization (12.6 +/- 7.9 vs 12.3 +/- 10.3) and pregnancy prolongation (22.3 +/- 13.5 vs 22.5 +/- 15.7). There were no differences between groups with respect to birth weight, incidences of small-for-gestational-age infants and preterm birth, number of days spent in special care unit, or cord blood gas measurement.\n Nifedipine therapy for preeclampsia reduces maternal blood pressure but does not reduce number of days of maternal hospitalization or improve perinatal outcome.", "Three hundred women with mild chronic hypertension at 6 to 13 weeks' gestation were randomly allocated to receive either methyldopa or labetalol or be in the control group. Thirty-seven women (12%) were excluded for various reasons. Of the remaining 263 patients, 90 received no drug, 87 received methyldopa, and 86 received labetalol. All 263 were followed throughout pregnancy with serial renal function tests and serial assessment of fetal status. There were no differences among the three groups in mean systolic or diastolic blood pressures, mean gestational age, or initial laboratory findings at time of entry. Patients treated with medications had significantly lower (p less than 0.0001) systolic and diastolic blood pressures throughout gestation compared with the no-medication group. Among the control group there was a spontaneously significant lowering (p less than 0.0001) of both systolic and diastolic blood pressures at 14 to 26 weeks' gestation. However, there were no differences among the three groups regarding the incidences of either superimposed preeclampsia (15.6%, 18.4%, and 16.3%, respectively), abruptio placentae (2.2%, 1.1%, and 2.3%, respectively), or preterm delivery (10%, 12.5%, and 11.6%, respectively). In addition, there were no differences among the groups regarding gestational age at delivery, birth weight, incidence of fetal growth retardation, or neonatal head circumference. There was one midtrimester loss in the methyldopa group and one stillbirth in each of the other groups. We conclude that treatment of maternal blood pressure in mild chronic hypertension during pregnancy did not improve perinatal outcome.", "To compare the effects of treatment with nicardipine and metoprolol in patients with hypertension during pregnancy.\n One hundred pregnant patients with mild or moderate hypertension followed at the Centre Hospitalier Intercommunal de Créteil (France) were randomly allocated to treatment with either nicardipine or metoprolol. Changes in maternal blood pressure (BP), laboratory indices, umbilical Doppler velocimetry, and neonatal outcome were compared by means of Student t test, chi 2 test, and analysis of variance.\n Nicardipine decreased maternal systolic and diastolic BP more than metoprolol (P < .001). Umbilical artery resistance was lower in nicardipine-treated patients (P < .001). Plasma uric acid and creatinine concentrations were increased less markedly in the nicardipine group (P < .05 and P < .01, respectively). The incidence of cesarean delivery for fetal distress was lower in the nicardipine group (P < .01). There was a trend toward higher birth weights in the nicardipine group but no significant difference in neonatal outcome.\n Nicardipine is more effective than metoprolol in decreasing maternal BP; neonatal outcome is not significantly different.", "Our purpose was to study the effects of isradipine, a dihydropyridine calcium channel blocker, on mother and fetus in the treatment of hypertensive disorders of pregnancy.\n The investigation was performed as a two-group, parallel, double-blind multicenter study of isradipine versus placebo. Fifty-four women were randomized to treatment with isradipine slow-release capsules given orally 5 mg twice a day and 57 to a placebo group.\n Isradipine lowered the maternal mean arterial blood pressure effectively in women with nonproteinuric hypertension but did not do so in women with proteinuria at recruitment or appearing during treatment. Blood flow in the umbilical artery and maternal renal and liver function were not influenced by treatment. Isradipine had few side effects and was well tolerated.\n Calcium channel blockade with isradipine is effective for treatment of nonproteinuric hypertension but not in preeclampsia.", "Twenty-five patients whose pregnancies were complicated by chronic hypertension were entered in a double-blind study and randomly allocated to treatment with methyldopa (Aldomet) or placebo. Thirteen patients were in the treatment group and 12 in the placebo group. The two groups showed no significant difference in demographic and pretreatment laboratory profiles. Methyldopa-treated patients registering in the first trimester had a significant reduction in the mean arterial pressure (MAP) during the second and third trimesters (P less than 0.025). No significant differences in birth weight (BW), ponderal index (PI) were found when results were corrected for gestational age (GA), race, and sex. The mean GA was significantly prolonged in the methyldopa-treated group by 10.3 days (P less than 0.05). The frequency of superimposed pre-eclampsia was similar in both groups (33.3% vs. 38.4%). However, 75% of the superimposed pre-eclampsia occurred antepartum in the placebo group, while 80% of the methyldopa-treated group developed superimposed pre-eclampsia intrapartum. The results of this small study suggest that the treatment of hypertension in pregnancy may reduce MAP and possibly delay the occurrence of superimposed pre-eclampsia and thus afford a prolongation of the pregnancy.", "Twentysix women with pregnancy-induced hypertension have been randomly treated with either labetalol or Aldomet. A more satisfactory control of blood pressure was obtained with labetalol with minimal side-effects. After two weeks of treatment with labetalol renal function had significantly improved with a markedly lower incidence of proteinuria. More patients went into spontaneous labour following labetalol than following Aldomet; the Bishop score was also higher in this group. No adverse effects attributable to labetalol were noted in the baby either ante- or post-natally.", "Atenolol was compared with placebo in a randomised and double-blind prospective study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest. Atenolol given once daily significantly reduced blood-pressure, prevented proteinuria, and reduced the number of hospital admissions. Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group, whose babies had a high morbidity. Respiratory distress syndrome occurred only in the placebo group. Intrauterine growth retardation, neonatal hypoglycaemia, and hyperbilirubinaemia occurred with the same frequency in the two groups. Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups. There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy. Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby.", "nan", "Two treatment strategies were compared in 155 women with pregnancy-induced hypertension who were also given comprehensive non-pharmacological care. The mean gestation at entry was 28 weeks. As long as the diastolic blood pressure (DBP) remained below 106 mmHg, oxprenolol, or oxprenolol plus dihydralazine, were given to the early treatment group, and matching placebos to the control group. Open antihypertensive treatment was provided for patients whose DBP rose above 105 mmHg. Proteinuria occurred in seven women in each group. In the early treatment group, 13 of the 78 women were delivered by caesarean section; the corresponding numbers in the control group were 27 of 76 (17 vs 36%, 95% confidence interval (CI) of difference: 5-33%); the sections included seven and 16 in the early treatment and control groups, respectively, for severe hypertension and/or fetal distress. There were five perinatal deaths, two in the early treatment group and three in the control group. Early treatment did not influence gestational age at birth or birthweight. Respiratory distress syndrome occurred in four infants in the early treated group and in 10 in the control group; 14 infants in the former group and 26 in the latter were in hospital for more than 10 days (18 vs 35%; 95% CI of difference 4-32%). These results indicate that early antihypertensive treatment with oxprenolol is safe for the fetus and newborn in pregnancy-induced hypertension, but has no advantage over non-pharmacological care in terms of fetal growth. However, it may prevent acute hypertension in late pregnancy and associated fetal distress, and thus reduce the number of caesarean sections.", "To determine the need for, and efficacy of, treatment with labetalol in women with mild-to-moderate pregnancy induced hypertension (PIH).\n Prospective double-blind randomised placebo controlled study.\n Maternity units of five hospitals in the Trent Region.\n 144 women (86 primigravid) who developed PIH after 20 weeks gestation.\n Treatment with oral labetalol up to 600 mg daily or placebo with subsequent care of treatment failures in accordance with the attending obstetrician's practice.\n Number of days spent as an antenatal inpatient; the development of proteinuria; the perceived need for induction of labour or elective caesarean section; and gestation age at delivery.\n Labetalol significantly lowered the blood pressure and reduced the incidence of proteinuria. However, neither the number of days spent as an antenatal inpatient, nor the perceived need for induction of delivery or elective caesarean section, nor the gestation age at delivery differed significantly between the two treatment groups. Post-randomisation consideration of early (< or = 32 weeks) and late (> 32 weeks) onset groups showed the placebo treated early-onset group (n = 15) to have more patients with severe hypertension (> 150/110 mmHg) and a greater requirement for additional antihypertensive therapy prior to labour than the group treated with labetalol (n = 16).\n Anti-hypertensive intervention therapy in pregnancy induced hypertension has been examined using a placebo controlled randomised double-blind trial of labetalol in pregnancy. The maximum blood pressure prior to labour and the incidence of proteinuria was reduced in women on active therapy. However, the length of gestation was not significantly prolonged and indices of clinical outcome were not significantly altered. The appropriateness of pharmacological therapy for late-onset PIH may be questioned.", "Fifty-one women with pregnancy-induced hypertension (PIH) were randomly allocated to one of three treatment groups: A: hydralazine (13); B: hydralazine and propranolol (17); and C: hydralazine and pindolol (19). All women fulfilled the pretreatment criteria and were of similar age, numbers of previous pregnancies and had systolic blood pressure (SBP) of between 140 and 160 mmHg and diastolic blood pressure (DBP) of between 95 and 110 mmHg. Hypertension was treated equally well by all three regimens (mean SBP was 133.6, 130 and 134 mmHg, respectively). Heart rate was significantly higher than baseline in group A and lower in groups B and C, as is to be expected with beta-blocker treatment. Side-effects were more frequent in group A than in groups B and C, 62% of the patients on hydralazine monotherapy complained of palpitations compared to 35% on combination treatment. Fetal outcome differed in the various groups. Birth weight was significantly lower in group B, where regimen included propranolol, compared to that of group C, for whom the regimen included pindolol (3,044.7 +/- 443.8 and 2,709.6 +/- 485.5 gm, p < 0.05). Mean blood glucose of the newborns were similar in groups A and C (76.5 +/- 16.5 and 78.6 +/- 15 gm%) and significantly lower in group B (62.6 +/- 14 gm%, p < 0.02). In conclusion, blood pressure was equally well treated in all three treatment groups. However, more maternal side-effects occurred in group A, the group treated with hydralazine monotherapy, while propranolol in combination with hydrazaline (group B) had some negative effects on fetal development which did not occur in pindolol/hydrazaline combination.", "Thirty patients matched for age, parity, socioeconomic status and severity of pregnancy induced hypertension (PIH) were randomly allocated to treatment with metoprolol or methyldopa. The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group; the mean birth weight of the babies was higher in cases treated with metoprolol. The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension.", "Labetalol was compared with methyldopa in a randomized controlled trial involving 176 pregnant women with mild to moderate hypertension. Diastolic blood pressure below 86 mmHg was obtained in a similar proportion of women given labetalol or methyldopa. Intrauterine death occurred in four women treated with methyldopa, and the one neonatal death on day 1 occurred in the labetalol group. The average birthweight and the proportion of preterm or small-for-gestational-age babies were similar in both groups. Heart rate, blood pressure, blood glucose, respiratory rate, and Silverman score of the babies did not differ between the two treatment groups, whether the comparison was made for all the infants, or only for those that were preterm or small-for-gestational-age. These data indicate that maternal beta-blockade with labetalol is as safe as methyldopa for the fetus and the newborn.", "One hundred pregnant women with hypertension (defined as diastolic blood pressure at or above 95 mm Hg) were allocated at random to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery. The patients were also stratified into those entering the study early (before 32 weeks' gestation) and those entering late (after 32 weeks' gestation). Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment, in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa; this difference remained throughout the treatment period. Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa. The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol; birth weight, placental weight, head circumference, and Apgar score were not significantly different and there were no stillbirths in either group." ]

[ "16273995", "18322263", "17509485", "22659994", "15829527", "19176895", "15326237", "19951274" ]

[ "Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study.", "Safety and efficacy of galantamine in subjects with mild cognitive impairment.", "Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study.", "A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI.", "Vitamin E and donepezil for the treatment of mild cognitive impairment.", "Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial.", "Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.", "A randomized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease." ]

[ "Mild cognitive impairment (MCI) causes memory impairment and executive function deficits in those with the condition. There is also some evidence that MCI patients are impaired in their daily functioning. Cholinesterase inhibitors have been widely used for patients with Alzheimer's disease (AD), with evidence of improving cognitive function. There is currently no established treatment for MCI, and cholinesterase inhibitors are beginning to be studied in these patients. Galantamine is a cholinesterase inhibitor that also has nicotinic receptor-modulating properties that has been successful in improving AD patients. This study examined the effects of galantamine in patients with MCI in areas of memory, executive functioning, and global functioning. There was a significant improvement in scores on the Functional Activities Questionnaire, which is a measure of global functioning. There were also improvements in the galantamine group on two of six measures in the Cambridge Automated Neuropsychiatric Test Assessment Battery and in immediate free recall on the California Verbal Learning Test.", "To assess the safety of galantamine in subjects with mild cognitive impairment (MCI), the ability of galantamine to benefit cognition and global functioning in subjects with MCI, and the ability of galantamine to delay conversion to dementia.\n In two studies, 2,048 subjects, 990 in Study 1 and 1,058 in Study 2, with a Clinical Dementia Rating (CDR) = 0.5, CDR memory score > or =0.5, without dementia were randomized to double-blind galantamine (16-24 mg/day) or placebo for 24 months. Primary efficacy endpoint at month 24 was number (%) of subjects who converted from MCI to dementia (CDR > or = 1.0).\n There were no differences between galantamine and placebo in 24-month conversion rates (Study 1: 22.9% [galantamine] vs 22.6% [placebo], p = 0.146; Study 2: 25.4% [galantamine] vs 31.2% [placebo], p = 0.619). Mean CDR-sum of boxes declined less with galantamine than placebo at 12 and 24 months in Study 1 (p = 0.024 [12 months] and p = 0.028 [24 months]), but not in Study 2 (p = 0.662 [12 months] and p = 0.056 [24 months]). Digit Symbol Substitution Test scores improved with galantamine in Study 1 at 12 months and in Study 2 at 24 months (Study 1: p = 0.009 [month 12] and p = 0.079 [Month 24]; Study 2: p = 0.154 [month 12] and p = 0.020 [month 24]). The most frequently reported adverse event was nausea (galantamine, 29%; placebo, 10%). Serious AEs occurred in 19% of each group. Mortality of the cohort after retrospectively determining the status of subjects (98.3%) at 24 months was 1.4% (galantamine) and 0.3% (placebo); RR (95% CI), 1.70 (1.00, 2.90).\n Galantamine failed to significantly influence conversion to dementia. Galantamine was generally well tolerated. Whereas recorded mortality was greater in the galantamine group than in the placebo group in the original per-protocol assessment, a post hoc analysis of the cohort was consistent with no increased risk.", "To assess the effect of rivastigmine in patients with mild cognitive impairment (MCI) on the time to clinical diagnosis of Alzheimer's disease (AD) and the rate of cognitive decline.\n The study was a double-blind, randomised, placebo-controlled trial of up to 48 months. All patients had MCI operationally defined by having cognitive symptoms, a global clinical dementia rating stage of 0.5, a score of less than 9 on the New York University delayed paragraph recall test, and by not meeting the diagnostic criteria for AD. Primary efficacy variables were time to clinical diagnosis of AD, and change in performance on a cognitive test battery. This study is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00000174.\n Of 1018 study patients enrolled, 508 were randomly assigned to rivastigmine and 510 to placebo; 17.3% of patients on rivastigmine and 21.4% on placebo progressed to AD (hazard ratio 0.85 [95% CI 0.64-1.12]; p=0.225). There was no significant difference between the rivastigmine and placebo groups on the standardised Z score for the cognitive test battery measured as mean change from baseline to endpoint (-0.10 [95% CI -0.63 to 0.44], p=0.726). Serious adverse events were reported by 141 (27.9%) rivastigmine-treated patients and 155 (30.5%) patients on placebo; adverse events of all types were reported by 483 (95.6%) rivastigmine-treated patients and 472 (92.7%) placebo-treated patients. The predominant adverse events were cholinergic: the frequencies of nausea, vomiting, diarrhoea, and dizziness were two to four times higher in the rivastigmine group than in the placebo group.\n There was no significant benefit of rivastigmine on the progression rate to AD or on cognitive function over 4 years. The overall rate of progression from MCI to AD in this randomised clinical trial was much lower than predicted. Rivastigmine treatment was not associated with any significant safety concerns.", "Mild cognitive impairment (MCI) is etiologically heterogeneous, and a substantial proportion of MCI subjects will develop different dementia disorders. One subtype of this syndrome, amnestic MCI, occurs preferentially but not exclusively in prodromal AD and is characterized by defined deficits of episodic memory.\n For a 2-year, double-blinded, placebo-controlled study MCI patients, presenting with an amnestic syndrome but not necessarily based on presumed prodromal AD were randomized.\n Patients received (a) a combination of 16 mg galantamine plus 20 mg memantine, or (b) 16 mg galantamine alone or (c) placebo.\n The primary objective was to explore the differential impact of these interventions on the progression to dementia and on cognitive changes as measured by the ADAScog.\n After recruitment of 232 subjects, the trial was halted before reaching the planned sample size, because safety concerns arose in other studies with galantamine in MCI. This resulted in a variable treatment duration of 2-52 weeks. The statistical analysis plan was amended for studying cognitive effects of discontinuing the study medication, which was done separately for galantamine and memantine, and under double-blind conditions. There was one death, no unexpected severe adverse events, and no differences of severe adverse events between the treatment arms. The cognitive changes on the ADAScog were not different among the groups. Only for the subgroup of amnestic MCI with presumed AD etiology, a significant improvement of ADAScog score over placebo before the discontinuation of medication was observed, while amnestic MCI presumably due to other etiologies showed no cognitive changes with broad variation. Cognitive improvement was numerically larger in the combination treatment group than under galantamine alone. Patients who received placebo declined as expected. Discontinuation of galantamine, either as part of the combination regimen or as mono treatment, resulted in a transient decline of the ADAScog score in amnestic MCI of presumed AD etiology, while discontinuation of Memantine did not change the cognitive status.\n In an interrupted trial with amnestic MCI subjects the combination of galantamine plus memantine were generally well tolerated. In the subgroup of MCI subjects with presumed AD etiology, a cognitive benefit of a short-term combination treatment of galantamine plus memantine was observed, and cognitive decline occurred after discontinuation of galantamine.", "Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease.\n In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function.\n A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers.\n Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.\n Copyright 2005 Massachusetts Medical Society.", "Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms.\n In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function.\n The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%).\n Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.", "To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI).\n A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations.\n Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient.\n Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.", "The safety and efficacy of early acetylcholinesterase inhibitors therapy in patients with cognitive impairment no dementia (CIND) after a cerebrovascular accident have not been examined. In this study, we investigated the safety and efficacy of rivastigmine in cognition, particularly executive function in patients with CIND because of cerebrovascular disease.\n This study was a 24-week, double-blind, randomized, placebo-controlled trial of ischemic stroke patients seen at a tertiary hospital who had cognitive impairment no dementia because of cerebrovascular disease. The intervention was either rivastigmine or placebo up to 9 mg/day. The primary outcome of interest was mean change from baseline in the Ten-Point Clock Drawing and Color Trails 1 and 2.\n Fifty patients were randomized into rivastigmine (n = 25) and placebo (n = 25) arms. Patients in the rivastigmine group showed statistically significant improvement (1.70 vs 0.13, P = 0.02) on the animal subtask of the verbal fluency measure compared with placebo. There was also a trend (non-significant) towards improvement in Color Trails II.\n In this pilot study, we demonstrated that rivastigmine was well tolerated in patients with CIND because of cerebrovascular disease and may potentially improve executive functioning." ]

[ "8713219", "18192510", "21323872" ]

[ "Efficacy of zinc therapy in prevention of crisis in sickle cell anemia: a double blind, randomized controlled clinical trial.", "Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia.", "Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043)." ]

[ "145 patients were recruited in the trial while 130 completed it. Patients were randomized to receive zinc sulphate capsules. 220 mgm three times a day or identical placebo. Major outcome variable was 'Sickle cell crisis'. After a follow up of 1.5 years, the mean number of episodes of crisis was 2.46 +/- 1.04 in the intervention group and 5.29 +/- 2.58 in the control group (p < 0.025; 95% CI for difference between groups: 1.98, 3.42). Mean duration of hospital stay was 4.3 +/- 2.2 days in the intervention group and 3.9 +/- 1.6 days in the control group. The difference was not significant (p > 0.05). There was a significant reduction of the mean number of infective episodes and associated morbidity in patients with sickle cell anaemia.", "Senicapoc, a novel Gardos channel inhibitor, limits solute and water loss, thereby preserving sickle red blood cell (RBC) hydration. Because hemoglobin S polymerization is profoundly influenced by intracellular hemoglobin concentration, senicapoc could improve sickle RBC survival. In a 12-week, multicenter, phase 2, randomized, double-blind, dose-finding study, we evaluated senicapoc's safety and its effect on hemoglobin level and markers of RBC hemolysis in sickle cell anemia patients. The patients were randomized into 3 treatment arms: placebo; low-dose (6 mg/day) senicapoc; and high-dose (10 mg/day) senicapoc. For the primary efficacy end point (change in hemoglobin level from baseline), the mean response to high-dose senicapoc treatment exceeded placebo (6.8 g/L [0.68 g/dL] vs 0.1 g/L [0.01 g/dL], P < .001). Treatment with high-dose senicapoc also produced significant decreases in such secondary end points as percentage of dense RBCs (-2.41 vs -0.08, P < .001); reticulocytes (-4.12 vs -0.46, P < .001); lactate dehydrogenase (-121 U/L vs -15 U/L, P = .002); and indirect bilirubin (-1.18 mg/dL vs 0.12 mg/dL, P < .001). Finally, senicapoc was safe and well tolerated. The increased hemoglobin concentration and concomitant decrease in the total number of reticulocytes and various markers of RBC destruction following senicapoc administration suggests a possible increase in the survival of sickle RBCs. This study is registered at http://clinicaltrials.gov as NCT00040677.", "Red blood cell (RBC) hydration is regulated in part by the Ca(2+) -activated K(+) efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo-controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty-five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52 weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0·38 vs. 0·31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups.\n © 2011 Blackwell Publishing Ltd." ]

[ "10363538", "12033074", "11399136", "15208209" ]

[ "Transitioning preterm infants with nasogastric tube supplementation: increased likelihood of breastfeeding.", "Cup or bottle for preterm infants: effects on oxygen saturation, weight gain, and breastfeeding.", "A pilot study to assess the viability of a randomised controlled trial of methods of supplementary feeding of breast-fed pre-term babies.", "Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial." ]

[ "To compare nasogastric tube and bottle supplementation as two means of transitioning preterm infants to breastfeeding within an established breastfeeding support program.\n Prospective, randomized controlled trial; mothers and health care providers, who were not blinded.\n Metropolitan private regional perinatal center; 40-bed intensive-care nursery.\n Eighty-four preterm breastfed infants whose birth weight was 1,000-2,500 g.\n Rates of exclusive and partial breastfeeding at discharge from the intensive-care nursery, and at 3 days, 3 months, and 6 months after discharge.\n Compared with infants receiving bottle supplements, infants receiving nasogastric tube supplements were more likely to be breastfeeding at discharge and at 3 days, 3 months and 6 months, after adjusting for confounding variables. Odds ratios (confidence intervals = 95%) showed that the group receiving nasogastric supplements was 4.5 times (1.4 to 15) more likely to be breastfed at discharge and 9.4 times more likely to be fully breastfed (3.1 to 28.4). There were significantly fewer apnea and bradycardia episodes in the group receiving nasogastric supplements, although they had more episodes that required stimulation for resolution. Groups were not different with respect to length of hospitalization and infant weight at discharge.\n Using nasogastric tube supplementation during transition to oral feedings increases the likelihood of breastfeeding at discharge, 3 days, 3 months, and 6 months. This intervention requires a program with skilled personnel and an environment that allows the mother and infant to be in close physical proximity. Further study should investigate differences in the effects on maternal confidence, imprinting, and suck mechanism when preterm infants are bottle fed and breastfed.", "The impact of cup-feeding or bottle-feeding on weight gain, oxygen saturation, and breastfeeding rates of preterm infants was studied in 34 bottle-fed and 44 cup-fed preterm infants. At initiation of oral feeding, postconceptional age and weight were 37.2 +/- 2.2 weeks and 1676 +/- 83 g for the bottle-fed group (BF) and 37.0 +/- 1.6 weeks and 1637 +/- 40 g for the cup-fed (CF) group, respectively. No significant differences between groups were found with regard to time spent feeding, feeding problems, weight gain, or breastfeeding prevalence at discharge or at 3-month follow-up. Possible beneficial effects of cup-feeding were lower incidence of desaturation episodes (13.6% vs 35.3%, CF vs BF, P = .024) and a higher prevalence of breastfeeding at 3 months among those still breastfeeding at the first follow-up visit (68.4% vs 33.3%, CF vs BF, P = .04).", "to compare the impact of two methods of supplementary feeding of pre-term babies (bottle vs cup) on subsequent breast feeding and to assess the feasibility of using a randomised controlled trial (RCT) to investigate the topic.\n small scale prospective RCT. Data on breast feeding, as defined as the exclusive method of feeding, were collected. A range of relevant bio-data was also collected and their impact on breast feeding assessed.\n a special care baby unit in a District General Hospital in the UK.\n over a three-month period, all pre-term babies (32-37 weeks' gestation) who fulfilled the inclusion criteria and has been born to mothers who had expressed a pre-partum desire to breast feed, who had consented to take part, were included (n=14).\n the eligible babies were randomly allocated to supplementary feeding of breast milk, via either a cup or a bottle. Whether or not the baby was being breast fed at discharge was noted.\n the study suggested that this RCT framework is a viable method of investigating baby feeding. Because of the small-scale nature of the project, the actual database must be treated with extreme caution. No significant differences were found between the two groups in terms of breast feeding. However, the mothers reported high levels of support and also the breast-feeding rates were above the national averages. These two findings could have contributed to the non-significant results observed in this analysis.\n if the present findings could be supported by further research, then the non-significant results relating method of supplementary feeds to subsequent breast feeding could be explained by reference to three factors. Firstly, there is, in fact, no real effect of method of supplementary feeding and subsequent breast feeding; secondly, the method adopted differed from existing research and thus may be expected to produce non-corroborative results; and finally, the overall levels of breast feeding within the Unit generally were higher than the national average. The relevance of the RCT for investigating this subject is also discussed with reference to the present data set. Further experimental work to develop these ideas and to identify causal links is required.\n Copyright 2001 Harcourt Publishers Ltd.", "To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants.\n Randomised controlled trial.\n Two large tertiary hospitals, 54 peripheral hospitals.\n 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate.\n Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial.\n Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. Secondary outcomes: prevalence of breast feeding at three and six months after discharge and length of hospital stay.\n 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01).\n Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay." ]

[ "9820298", "6712366", "2775618", "2735986", "3295148", "11602412", "9352146", "9755836", "3538957", "3816105", "8518376", "8513386", "2127324", "11735759", "8181203", "11872193", "2745867", "2057991", "1505605", "9154031", "8513660", "1905602", "10927732" ]

[ "Multicentre randomised study of computerised anticoagulant dosage. European Concerted Action on Anticoagulation.", "Clinical studies with computer-assisted initial lidocaine therapy.", "Individualised aminoglycoside dosage based on pharmacokinetic analysis is superior to dosage based on physician intuition at achieving target plasma drug concentrations.", "Computer-assisted optimization of aminophylline therapy in the emergency department.", "Initiation of warfarin therapy: comparison of physician dosing with computer-assisted dosing.", "Effect of computer-aided management on the quality of treatment in anticoagulated patients: a prospective, randomized, multicenter trial of APROAT (Automated PRogram for Oral Anticoagulant Treatment).", "Comparison of oral anticoagulant control by a nurse-practitioner using a computer decision-support system with that by clinicians.", "A randomized comparison of a computer-based dosing program with a manual system to monitor oral anticoagulant therapy.", "A randomized controlled clinical trial of pharmacokinetic theophylline dosing.", "Evaluation of three dosage-prediction methods for initial in-hospital stabilization of warfarin therapy.", "Midazolam and fentanyl continuous infusion anesthesia for cardiac surgery: a comparison of computer-assisted versus manual infusion systems.", "A new sodium-nitroprusside-infusion controller for the regulation of arterial blood pressure.", "Impact of a clinical pharmacokinetic service on patients treated with aminoglycosides: a cost-benefit analysis.", "Guided medication dosing for inpatients with renal insufficiency.", "A prospective randomized comparison of the accuracy of computer-assisted versus GUSTO nomogram--directed heparin therapy.", "A computerized decision support system for ovarian stimulation by gonadotropins.", "A prospective randomised trial comparing individualised pharmacokinetic dosage prediction for aminoglycosides with prediction based on estimated creatinine clearance in critically ill patients.", "Outpatient management of warfarin therapy: comparison of computer-predicted dosage adjustment to skilled professional care.", "Computer assisted design of a theophylline dosing regimen in acute bronchospasm: serum concentrations and clinical outcome.", "Evaluation of a decision support system for initiation and control of oral anticoagulation in a randomised trial.", "A randomized controlled trial of computerized pharmacokinetic theophylline dosing versus empiric physician dosing.", "A controlled trial of the cost benefit of computerized bayesian aminoglycoside administration.", "Oral anticoagulation management in primary care with the use of computerized decision support and near-patient testing: a randomized, controlled trial." ]

[ "The demand for anticoagulant treatment is increasing. We compared the benefits of computer-generated anticoagulant dosing with traditional dosing decided by experienced medical staff in achieving target international normalised ratios (INRs).\n In five European centres we randomly assigned 285 patients in the stabilisation period and stabilised patients to the computer-generated-dose group (n=137) or traditional-dose group (n=148). Centres had a specialist interest in oral anticoagulation but no previous experience with computer-generated dosing. The computer program calculated doses and times to next visit. Our main endpoint was time spent in target INR range (Rosendaal method).\n For all patients combined, computer-generated dosing was significantly beneficial overall in achieving target INR (p=0.004). The mean time within target INR range for all patients and all ranges was 63.3% (SD 28.0) of days in the computer-generated-dose group compared with 53.2% (27.7) in the traditional-dose group. For the stabilisation patients alone, computer-generated doses led to a non-significant benefit in all INR ranges (p=0.06), whereas in the stable patients the benefit was significant (p=0.02).\n The computer program gave better INR control than the experienced medical staff and at least similar standards to the specialised centres should be generally available. Clinical outcome and cost effectiveness remain to be assessed.", "A randomized prospective study compared achievement and maintenance of therapeutic plasma concentrations in patients receiving computer-assisted (CA) initial lidocaine hydrochloride therapy, designed pharmacokinetically to achieve and maintain a chosen plasma concentration, v conventional lidocaine therapy (CT). A separate audit of outcome was also conducted. The CA regimens provided more effective concentrations in the first hour than did CT, 2.65 v 1.5 micrograms/mL average. In the audit, ventricular fibrillation occurred in two of 78 CA v eight of 78 CT patients. Dosage adjustments were required in two CA patients v 33 CT patients. The CA therapy improved therapeutic precision, reduced dosage adjustments, and may have improved safety during initial lidocaine therapy before fitting to plasma concentration data for subsequent feedback. An improved clinical computer program now also fits to plasma concentration data. It is accessed and used routinely by hospitals over an international time-sharing network.", "1. A prospective randomised trial was conducted to compare aminoglycoside dose prediction based on individually measured pharmacokinetic data, with dosage based on physician intuition. 2. After 2 days of therapy more patients in the pharmacokinetic group had achieved both peak (6-10 mg 1(-1] and trough (1-2 mg 1(-1] target plasma concentrations (P = 0.007), peaks alone (P = 0.01) and troughs alone (P = 0.01). Their mean (s.e. mean) peak concentration was 6.49 +/- 0.39 mg 1(-1) compared with 4.27 +/- 0.52 mg 1(-1) in the control group (P = 0.001), with trough concentrations of 1.44 +/- 0.22 mg 1(-1) and 0.94 +/- 0.21 mg 1(-1) respectively (P = 0.054). 3. After 5 days of therapy, peak and trough concentrations were still significantly higher in the pharmacokinetic group despite empirical dose adjustment (P = 0.01 and P = 0.013 respectively). 4. The mean (s.e. mean) daily dose of aminoglycoside was higher in the computer group (312 +/- 17 mg vs 203 +/- 13 mg, P = 0.001). 5. These findings suggest that dose estimation based on measured pharmacokinetic parameters is superior at achieving target plasma drug concentrations.", "The emergency department (ED) is a unique setting for pharmacokinetic-guided drug administration because of the need to rapidly optimize therapy. We compared outcomes in patients receiving intravenous aminophylline according to population-based ED guidelines (group 1) or Bayesian-derived pharmacokinetic estimates (group 2), we determined predictors for admission or discharge in our study group, and we assessed the ability of a Bayesian pharmacokinetic model to estimate theophylline requirements in the ED. The study population was composed of 82 patients (42 males, 40 females) with a mean age of 43 +/- 15.5 years. Fifteen patients were excluded because of protocol violations. Of the 67 cases studied, 30 were assigned to group 1, and 37 were assigned to group 2. Patient demographics, baseline theophylline concentration, and theophylline loading dose did not differ significantly between treatment groups. The aminophylline maintenance infusion was significantly (P less than .001) lower in group 1 (0.4 +/- 0.2 mg/kg/h) than in group 2 (0.6 +/- 0.2 mg/kg/h). Serum theophylline concentrations at one hour post-loading-dose did not differ significantly between treatment groups; however, significant differences were observed at two hours post-load (P less than .002) and four hours post-load (P less than .001). Baseline peak flow rate (PFR) was significantly (P less than .03) higher in group 1 (170 +/- 85 L/min) than in group 2 (132 +/- 62 L/min), but did not differ significantly at any other times throughout the study. The PFR one hour post-load (PFR-1) was the strongest (P less than .003) predictor of outcome.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a prospective, randomized study at two university hospitals, the authors examined how effectively housestaff physicians (n = 36) managed the initiation of warfarin therapy compared with a computer-assisted dosing regimen (n = 39) using the software program Warfcalc, which was managed by one of the authors. Target prothrombin time ratios were selected by the physicians. Study endpoints included: the time to reach a therapeutic prothrombin ratio, the time to reach a stable therapeutic dose, the number of patients transiently overanticoagulated, the number of bleeding complications, and the accuracy of the predicted maintenance dose, which was assessed at steady-state 10-14 days later. Computer-assisted dosing consistently out-performed the physicians: a stable therapeutic dose was achieved 3.7 days earlier (p = 0.002), fewer patients were overanticoagulated (10% versus 41%), and the predicted maintenance dose was in the therapeutic range in 85% of the computer-dosed patients versus 42% of the physician group (p less than 0.002). For physicians who did not routinely manage warfarin therapy, computer-assisted dosing improved the accuracy of dosing and shortened the time required to achieve a stable therapeutic dose.", "We carried out a prospective, randomized trial to test whether a computer-based decision support system to initiate and maintain oral anticoagulant (OA) treatment can improve the laboratory quality of therapy.\n Two separate sets of patients on oral anticoagulants, in five Italian anticoagulant clinics, were studied: 335 patients in the first three months of treatment (stabilization phase), 916 patients (775 patient-years) beyond the third month of treatment (maintenance phase). Patients were randomized to a computerized system, which included algorithms able to suggest OA dosing and to schedule appointments (computer-aided dosing) or to an arm in which OA were prescribed by the same teams of expert physicians without such algorithms (control group). Primary outcomes were: A) the percentage of patients reaching a stable state of anticoagulation during each of the first three months of treatment; B) the percentage of time individuals spent within the aimed therapeutic range (maintenance phase).\n Patients in the computer-aided dosing group achieved a stable state significantly faster (p<0.01) and they spent more time within the therapeutic range during maintenance (p<0.001) than controls. The favorable effect of computer-aided dosing was mainly due to a reduction of the time spent below the therapeutic range and was associated with an increase of mean INR value, of anticoagulant drug dosage, and with a reduction of the number of appointments per patient (all changes significant: p<0.001).\n The computer decision-aided support improves the laboratory quality of anticoagulant treatment, both during long-term maintenance and in the early, highly unstable phase of treatment, and it also significantly reduces the number of scheduled laboratory controls.", "With increasing work-loads in anticoagulant clinics different methods of service delivery need evaluation. The quality of anticoagulant control achieved by a nurse-practitioner using a computer decision-support system (CDSS) was compared with that achieved by trainee doctors without CDSS. Eighty-one out-patients (group A, therapeutic range 2-3) and 96 out-patients (group B, therapeutic range 3-4.5) were randomized to management by a nurse-practitioner or by trainee doctors (clinicians). Thirty-seven patients in group A and 50 patients in group B were randomized to be managed by the nurse-practitioner. In group A, patients in the nurse-practitioner group spent a longer time in the therapeutic range than those in the clinician group (60.7% compared with 51.6%). Dose suggestion acceptance in the nurse-practitioner group (88%) was higher compared with agreement between the CDSS and the clinicians (60%). In group B, patients in the clinician group spent a slightly longer time in the therapeutic range (70% compared with 67.6%). Acceptance of dose suggestion was lower in the nurse-practitioner group (67%) compared with agreement between the CDSS and the clinicians (73%). In conclusion, the CDSS can improve the quality of control of warfarin therapy by a nurse-practitioner over that by trainee doctors for the therapeutic range 2-3. Similar quality of control is achieved for the therapeutic range 3-4.5. The CDSS may be used by nurse-practitioners to achieve safe and effective anticoagulation in hospital-based or out-reach anticoagulant clinics.", "nan", "Ninety-one patients admitted to hospital with acute air-flow obstruction and requiring theophylline therapy were randomly assigned to either a monitored or a control group. Intravenously administered and subsequent orally administered theophylline dosages for patients in the monitored group were adjusted daily on the basis of each patients's estimated theophylline clearance; dosages for control patients were determined by attending physicians, using knowledge of theophylline serum concentrations. During intravenous therapy, fewer monitored than control patients had serum theophylline concentrations in the toxic range (18.9 versus 37.8%, p = 0.04), and during subsequent oral therapy more monitored than control patients had serum theophylline concentrations in the therapeutic range (71.1 versus 44.4%, p = 0.018). There was a trend for peak expiratory flow rates to normalize more quickly in monitored patients, and their mean duration of hospital stay was shorter (6.3 versus 8.7 days, p = 0.029). Two patients in the control group died; both had theophylline concentrations above 25 micrograms/ml and clinical toxicity. No serious side effects were observed in the monitored group. With pharmacokinetic individualization of theophylline dosage, more patients achieved serum concentrations in the therapeutic range, and there was a tendency for more rapid clinical improvement.", "Three dosage-prediction methods for initial in-hospital stabilization of warfarin therapy were evaluated. Adult inpatients who had received warfarin sodium 10 mg daily for less than three days were eligible for the study. After receiving their third warfarin dose, patients were randomly assigned to have their warfarin dosages adjusted using one of three dosage-prediction methods: by analog computer (n = 31), linear regression (n = 22), or empiric dosing by the physician (n = 34). A prothrombin time (PT) ratio (patient PT divided by control PT) between 1.3 and 2.5 was considered to be in the therapeutic range. For patients who achieved a stable PT ratio (defined as a PT ratio between 1.3 and 2.5 that varied by less than 0.05 on two consecutive days or by less than 0.1 on three consecutive days without a dosage change) before discharge, the number of days (time to stabilization) from administration of the first warfarin dose to achievement of the warfarin dosage that produced a stable PT ratio (stabilization dosage) was compared. A total of 54 patients met the study criteria for a stable PT ratio before hospital discharge (analog computer, n = 20; linear regression, n = 15; empiric dosing, n = 19). The mean times to stabilization were 6.8 days in the analog-computer group, 7.3 days in the linear-regression group, and 8.4 days in the empiric-dosing group; these times were not significantly different. All 20 stabilized patients in the analog-computer group achieved a stable PT ratio by the fourth dosage prediction.(ABSTRACT TRUNCATED AT 250 WORDS)", "Continuous infusion of intravenous anesthetics can be achieved either by a manually controlled infusion (MCI) pump, or by a computer-assisted continuous infusion (CACI) pharmacokinetic model-driven infusion system. Randomized double-blind comparisons of the two infusion systems for general anesthesia were performed in 24 patients undergoing coronary artery bypass grafting. Patients were allocated to receive continuous infusions of midazolam and fentanyl by either a MCI device or CACI. Midazolam and fentanyl infusions were independently titrated to maintain hemodynamic stability, defined as mean arterial pressure (MAP) and heart rate (HR) within 20% of baseline values. As directed by the study design, comparable hemodynamic control was achieved in both groups. Mean plasma fentanyl concentrations measured at specific timepoints were similar between groups. The plasma midazolam level for induction was 196 +/- 139 ng/mL in the CACI group and 300 +/- 128 ng/mL in the MCI group, and the fentanyl level was similar in both groups, 6.7 +/- 1.9 ng/mL in CACI and 6.3 +/- 4.6 ng/mL in the MCI group. The drug levels were lower (P < or = .05) for midazolam during maintenance of anesthesia and similar for fentanyl during the maintenance of anesthesia. In the MCI group, the average duration of anesthesia was 246.5 +/- 35.0 minutes, with a mean total fentanyl dose of 30.27 +/- 11.14 micrograms/kg. In the CACI group, the average duration of anesthesia was 230.8 +/- 44.1 minutes, with a mean total fentanyl dose of 34.61 +/- 5.40 micrograms/kg (P > 0.05 for comparisons between groups for duration of anesthesia and total fentanyl dose).(ABSTRACT TRUNCATED AT 250 WORDS)", "Automatic optimization of the infusion rate of sodium nitroprusside (SNP) is achieved by an integrated hardware-software closed-loop controller implemented as a small bedside device. A microprocessor-based blood pressure monitor controls an infusion pump. The shape of the arterial pressure wave is digitally sampled; its analysis incorporates artifact-detection and -rejection routines. The implemented algorithm applies a rule-based closed-loop control that incorporates fuzzy logic. The system models the decision-making ability of the expert, instead of trying to model the patient's physiologic dynamics. Several internal fuzzy-state variables are defined to achieve a clear understanding of mean arterial pressure (MAP) evolution with time. The system performance is very robust, employing, under all possible situations, a sort of \"common sense.\" A clinical trial of the controller was conducted in 60 patients requiring vasodilation therapy for systemic arterial hypertension following cardiac surgery, 20 who had conventional manual control by an experienced nursing staff and 40 who had automated closed-loop control. The first 240 minutes of the postoperative period were closely watched, taking into account 1) the percentage of time during which MAP was within the 10-mmHg wide frame above the target pressure (target gap); 2) the mean difference of pressure values that crossed the boundary of the target gap; 3) the mean SNP-infusion rate. With automatic control, the time mean arterial pressure values were located in the target gap during the first hour amounted to 72.8 +/- 6.7%, vs 51.2 +/- 10.3% in the manual-control group. In the second hour, it was 79.3 +/- 2.5% vs 67.4 +/- 11.7% (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)", "In a prospective, randomized study, 75 adults receiving aminoglycosides were followed by a clinical pharmacokinetic service and 70 followed as controls. The two groups were similar in age, gender, height, and APACHE II score. A cost-to-charge ratio was used to derive direct costs of hospitalization and calculate cost-benefit. Excluded from this comparison were patients with incomplete acceptance of pharmacokinetic service recommendations and patients followed by other clinical pharmacists. Pharmacokinetic service patients had shorter hospitalizations (322.67 +/- 270.28 h; controls 442.89 +/- 536.81, p = 0.087) and febrile periods (50.05 +/- 79.38 h; controls 92.23 +/- 122.50, p less than 0.05). More pharmacokinetic service patients had adequate peak levels. Pharmacokinetic service direct costs were lower ($7,102.56 +/- 9,898.19; controls $13,758.64 +/- 22,874.31, p less than 0.05). Calculated direct cost of the service was $85.00/patient. Annual savings for 500 patients is $2,220,540.00.", "Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error.\n To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes.\n Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital.\n Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed.\n Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods.\n A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization.\n Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.", "Failure to adequately anticoagulate the blood of patients receiving recombinant tissue plasminogen activator (TPA) leads to greater rates of rethrombosis. In a multicentered, randomized trial in 51 patients we compared the ability to achieve and maintain therapeutic anticoagulation by use of computer-assisted heparin therapy or the GUSTO (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) heparin nomogram guidelines in patients with myocardial infarction treated with recombinant TPA. Heparin therapy was initiated with either computer-generated starting doses or GUSTO guideline starting doses. Activated partial thromboplastin times were measured every 6 to 8 hours for the first 24 hours. The therapeutic range used in this trial was 1.5 to 2.5 times the patient's baseline activated partial thromboplastin time (APTT). Ninety-four percent of the APTT ratios in the computer group were equal to or greater than 1.5 in the first 24 hours compared with 78% in the GUSTO group (p < 0.009). No significant difference in bleeding was found (7.7% for GUSTO; 4.2% for computer). Incremental time-dependent changes in heparin dose were found (day 1, 1110 +/- 243 units/hr, APTT ratio = 2.5 +/- 1.4; day 3, 1380 +/- 374 units/hr, APTT ratio, 1.9 +/- 0.4). Computer-assisted heparin therapy TPA results in superior anticoagulation accuracy compared with the GUSTO guidelines. In addition, the pharmacodynamic response to heparin changes in the 2 to 3 days after administration of TPA, leading to greater heparin requirements.", "To evaluate the effectiveness of a computerized decision support system for ovarian stimulation with gonadotropins.\n Retrospective and prospective randomized studies.\n Private and university teaching hospital.\n Women undergoing ovarian stimulation to treat infertility.\n Pregnancy rate.\n In the retrospective study, computer-generated decisions were compared with clinicians' decisions in 118 stimulated cycles in 53 patients. In 90% of cases, the choice of FSH regimens and adjustments to dosages were identical. In the prospective study, the computer-generated decisions achieved a pregnancy rate per cycle of 18% (15 of 82 cycles), compared with 16% (13 of 82 cycles) achieved by clinicians.\n A computerized decision making system was as effective as skilled clinicians in achieving pregnancy by using ovarian stimulation with FSH.", "A prospective randomised trial was conducted in critically ill patients to evaluate a computer aided pharmacokinetic method of aminoglycoside dose prediction based on 3 measured plasma concentrations following the loading dose. The ability of this method to achieve therapeutic plasma aminoglycoside concentrations early in the course of treatment was compared with that of a nomogram approach based on creatinine clearance estimated using the formula of Cockroft and Gault. Ninety-two percent of patients in the computer group achieved peak plasma concentrations within the optimum range of 6-10 mg/l at 48-72 h compared with 21% of control group patients (p = 0.0009). The mean peak plasma concentration of 7.45 mg/l at 48-72 h in the computer group was closer to the target concentration of 8 mg/l than was the 5.14 mg/l in the control group (p = 0.0004). There was no significant difference between the groups in measured indices of renal function, both groups showing an improvement in mean estimated creatinine clearance from the beginning to the end of the course of treatment. Dosing based on individualised pharmacokinetic data is therefore a more reliable method of achieving therapeutic blood concentrations early in the course of treatment than is nomogram based dosing. Other studies suggest that this should be associated with a reduction in mortality in severe infections.", "In a prospective, randomized clinical trial, we compared the accuracy of warfarin dosage-adjustments predictions using a computer program to the skill of an experienced anticoagulation nurse-specialist. The computer program predicts the steady state warfarin dose by applying Bayesian forecasting techniques to a mathematical model of the dynamic pharmacologic response to warfarin. Fifty patients who were receiving chronic warfarin therapy and who required a dosage adjustment because their prothrombin time was greater than or equal to 2 s away from their target prothrombin time were enrolled. The baseline characteristics of each group were similar, including the mean of the absolute value of the differences between initial prothrombin times and corresponding target prothrombin times. After a new a new warfarin dose was predicted, the prothrombin time was measured at least 7 days after dosage adjustment. Overall, the results in each group were comparable. There was no significant difference between groups and the mean of the absolute value of the differences between final prothrombin times and target prothrombin times, nor was there a difference in the proportion of patients who had a final prothrombin time within 2 s of the target prothrombin time. We conclude that the accuracy of warfarin dosage adjustments made using computer modeling is comparable to the skill of an anticoagulation nurse-specialist.", "The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed, comparing the results achieved by computer-assisted dosing, designed to achieve and maintain a serum theophylline level of 16 micrograms.ml-1 (10 patients) with those of unaided physicians (15 control patients). The outcome measures compared were clinical improvement, peak expiratory flow rate and serum theophylline concentration. Loading doses of theophylline in the control and computer groups were: 167 and 437 mg, respectively. Initial serum theophylline concentrations, measured 20 min after the loading dose, were 13.6 and 17.0 micrograms.ml-1 in the control and computer groups, respectively. In patients who had not received theophylline prior to admission, loading doses and initial concentrations were: 200 mg and 9.4 micrograms.ml-1 in the control group (n = 5) versus 613 mg and 15.7 micrograms.ml-1 in the computer group (n = 4), respectively. During maintenance therapy, serum theophylline concentrations were kept in the therapeutic range (10-20 micrograms.ml-1) throughout 51% and 77% of the hospitalisation period, in the control and computer groups, respectively. There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate. The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm. There was no correlation between clinical outcome and serum theophylline concentration, but this may have been due to the small sample size and modest difference in serum theophylline between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine whether a computerised decision support system for initiation and control of oral anticoagulant treatment improves quality of anticoagulant control achieved by trainee doctors.\n Randomised controlled trial.\n District general hospital in North London.\n 148 inpatients requiring start of warfarin treatment.\n Management by trainee doctors (to achieve therapeutic range of international normalised ratio of 2 to 3) with indirect assistance from computerised decision support system (intervention group) or without such assistance (control group).\n Median time to therapeutic range, stable dose, and first pseudoevent (excessive international normalised ratio after therapeutic range has been reached) and person time spent in the therapeutic range.\n 72 patients were randomised to the intervention group and 76 to control group. Median time to reach international normalised ratio of > or = 2 was not significantly different in the two groups (3 days). Median time to achieve a stable dose was significantly lower in intervention group than in controls (7 days v 9 days, P = 0.01) without excessive overtreatment or undertreatment with anticoagulant. Patients in intervention group spent greater proportion of time in therapeutic range, both as inpatients (59% v 52%) and outpatients (64% v 51%).\n The computerised decision support system was safe and effective and improved the quality of initiation and control of warfarin treatment by trainee doctors.", "This study was undertaken to determine if a computerized pharmacokinetic program for adjusting theophylline infusion rates could attain a goal serum theophylline level more accurately than physician-derived adjustments and what clinical impact this would have. Thirty-five patients with diagnoses of asthma or chronic obstructive pulmonary disease were randomized to a control group (empiric) or experimental group (kinetic) after initial theophylline levels were drawn from each group. After second levels were drawn, patients in the kinetic group had their infusion rates adjusted by the computerized pharmacokinetic program to achieve a level of 15 mg/L, whereas patients in the empiric group had their infusions adjusted empirically by the primary care physicians to achieve a serum theophylline level of 15 mg/L. A final theophylline level was obtained just before the infusion was discontinued. The kinetic group was closer to the goal level of 15 mg/L than the empiric group, but this was not statistically significant (14.8 +/- 4.4 versus 12.6 +/- 4.1; p > 0.05). The total number of days that patients were receiving intravenous theophylline was slightly longer for the kinetic group (4.1 +/- 3.3 versus 3.2 +/- 1.5; p > 0.05) as was the total number of hospital days, but neither of these were statistically significant (11.4 +/- 21.6 versus 8.8 +/- 15.4 days; p > 0.05). There were no differences between the two groups in the number of subtherapeutic or toxic levels, and there were no significant differences in arterial blood gas measurements.(ABSTRACT TRUNCATED AT 250 WORDS)", "We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections. Patients were randomized to a control (dosing based on physician choice; n = 75) or experimental group (dosing based on the bayesian program; n = 72). Both groups used serum aminoglycoside concentration data when making dosing decisions. Improved response rates were seen in the experimental (60%; 42/68) compared with the control group (48%; 36/68). A higher, but not statistically significant, incidence of toxicity was found in the control (7/75; 9.7%) versus the experimental group (4/72; 5.1%). Mean length of total hospital stay was significantly longer for patients in the control group (20.3 days) compared with the experimental group (16.0 days) (p = 0.028). The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy. On the basis of a reduced length of stay, a potential cost savings of $1311 per patient can be achieved.", "There is increased pressure on primary care physicians to monitor oral anticoagulation.\n To test the null hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic, involving near-patient testing and computerized decision support software, compared with routine hospital management based on a variety of clinical outcome measures.\n A randomized, controlled trial in 12 primary care practices in Birmingham, England (9 intervention and 3 control). Two control populations were used: patients individually randomly allocated as controls in the intervention practices (intrapractice controls) and all patients in control practices (interpractice controls). Intervention practices' patients were randomized to the intervention (practice-based anticoagulation clinic) or control (hospital clinic) group. The main outcome measure was therapeutic control of the international normalized ratio.\n Three hundred sixty-seven patients were recruited (122 intervention patients, 102 intrapractice control patients, and 143 interpractice control patients). Standard measures of control of the international normalized ratio (point prevalence) showed no significant difference between the intervention and control groups. Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group (paired t test, P =.008).\n Nurse-led anticoagulation clinics can be implemented in novice primary care settings by means of computerized decision support software and near-patient testing. Care given by this model is at least as good as routine hospital follow-up. The model is generalizable to primary health care centers operating in developed health care systems." ]

[ "10214735", "3931138", "8960716", "2642499", "3114812", "2189429", "10463377", "10665618", "6753611", "2392216", "7554703" ]

[ "A 24-week randomized trial of controlled-release physostigmine in patients with Alzheimer's disease.", "Efficacy of oral physostigmine in primary degenerative dementia. A double-blind study of response to different dose level.", "A multicenter double-blind study of controlled-release physostigmine for the treatment of symptoms secondary to Alzheimer's disease. Physostigmine Study Group.", "Chronic oral physostigmine without lecithin improves memory in Alzheimer's disease.", "Intravenous physostigmine treatment of Alzheimer's disease evaluated by psychometric testing, regional cerebral blood flow (rCBF) measurement, and EEG.", "Oral physostigmine as treatment for primary degenerative dementia: a double-blind placebo-controlled inpatient trial.", "Double-blind, randomized, placebo-controlled clinical trial on the efficacy and tolerability of a physostigmine patch in patients with senile dementia of the Alzheimer type.", "Extended-release physostigmine in Alzheimer disease: a multicenter, double-blind, 12-week study with dose enrichment. Physostigmine Study Group.", "Enhancement of memory processes in Alzheimer's disease with multiple-dose intravenous physostigmine.", "The effect of long-term physostigmine administration in Alzheimer's disease.", "Clinical pharmacokinetics of physostigmine in patients with Alzheimer's disease." ]

[ "To evaluate the safety and efficacy of controlled-release physostigmine, an acetylcholinesterase inhibitor, in patients with probable AD of mild to moderate severity.\n A prospective, 24-week, randomized, multicenter, double-blind, parallel group study of patients was conducted. The study enrolled 475 patients at 24 sites. Patients met criteria for probable AD and were randomized to one of three arms: placebo, controlled-release (CR) physostigmine 30 mg daily, or CR physostigmine 36 mg daily. Dosage was escalated by a forced upward titration during the first 6 to 9 weeks of the trial, then maintained at a constant dose to 24 weeks. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change-Plus with caregiver input (CIBIC+). Secondary outcome measures included the Clinical Global Impression of Change (CGIC), the Geriatric Evaluation by Relatives Rating Instrument, and an Instrumental Activities of Daily Living Scale.\n In an intent-to-treat population, the last observation carried forward analysis revealed a 2.9-point ADAS-Cog (p = 0.002) difference between physostigmine and placebo-treated patients for both dosages, and a 0.26 to 0.31-point difference on the CIBIC+ (p = 0.048). There were no significant differences on the secondary outcome measures except for a difference on the CGIC when analyzed by use of the Cochran-Mantel-Haenszel statistic (p = 0.014). There were significant increases in gastrointestinal side effects including nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain for patients on either dose of physostigmine, resulting in a high dropout rate. Agitation was decreased significantly. There was no evidence of cardiac rhythm disturbance or liver function abnormalities.\n CR physostigmine enhanced cognitive and global function. It is relatively safe for the treatment of cognitive dysfunction secondary to AD. However, in light of the gastrointestinal side effects, a lower starting dose and a flexible titration schedule might lead to a more favorable adverse event profile in the clinical arena.", "To examine the efficacy of cholinergic enhancement in senile dementia of the Alzheimer type (SDAT), oral physostigmine was given to eight patients in a cross-over trial of three dose levels and a matching placebo. A dose-related improvement in memory as measured by objective verbal memory tests was observed. Performance was significantly better on the highest dose, 2 mg every 2 h, than on the lower doses. The effect was most systematically present for very short-term memory, which raises the question of whether the improvement may involve attention rather than longer term storage and retrieval.", "A multicenter trial to evaluate the efficacy of controlled-release physostigmine salicylate, a cholinesterase inhibitor, was conducted in 1,111 mild-to-moderate Alzheimer's disease (AD) subjects.\n During dose titration, subjects received 18, 24, or 30 mg of physostigmine or placebo daily. After a 2-week washout period, 366 subjects with putative improvement were randomized to receive either placebo or their best dose of physostigmine in a 6-week double-blind trial. Nonresponding patients (439) were randomized to receive in a separate double-blind trial either placebo or their highest tolerated dose of physostigmine. The primary efficacy measures included the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) and a Clinical Global Impression of Change (CGIC). Secondary measures included the Mini-Mental State Examination and two activities-of-daily-living scales.\n At the end of the 6-week double-blind phase, physostigmine-treated patients scored 1.75 points higher than placebo-treated patients on the ADAS (p = 0.003) and 0.26 points higher on the CGIC (p = 0.012) in the intent-to-treat analysis. There was no significant improvement on the secondary outcome measures. Patients failing to respond to physostigmine during the dose titration phase failed to respond on any of the outcome measures during the double-blind period of re-exposure. Common adverse events included nausea, vomiting, diarrhea, and anorexia. There were no significant changes in liver function tests.\n This study demonstrated statistically significant differences between physostigmine and placebo on both a performance-based cognitive functioning instrument and a clinician's global evaluation. The magnitude of the effect size was small and occurred only in the subset of patients who responded in the initial dose titration study period. Nevertheless, the results suggest that in a subset of patients, physostigmine can induce a degree of cognitive improvement over 6 weeks of treatment.", "Sixteen patients with early Alzheimer's disease (AD) completed a 3-month outpatient double-blind parallel trial of oral physostigmine versus placebo. Ten subjects received drug; six received placebo. After a dose-titration phase, each patient was placed on his or her best dose of drug or placebo. Subjects were evaluated with both memory and nonmemory tasks. Seven of the ten drug-treated patients, but none of the six placebo-treated patients, demonstrated improvement on a selective reminding task, a test of verbal memory. Family members reported improvement in six of ten drug-treated patients and none of six placebo-treated individuals. There was a trend toward greater improvement with increasing drug dose. There was no improvement on the nonmemory tests administered. The data indicate that oral physostigmine improves memory but not other areas of cognition.", "Ten patients with Alzheimer's disease were treated with intravenous infusion of physostigmine for 2 h. The acute effects on cognitive function, regional cerebral blood flow, and EEG were compared to placebo (isotonic glucose) using a double-blind cross-over design. Physostigmine causes a limited improvement of psychomotor performance and EEG and an increase of blood flow in the most severely affected cortical areas, predominantly in an early phase of Alzheimer's disease.", "Twenty-three patients with primary degenerative dementia (Alzheimer's disease) were administered an optimal dose of oral physostigmine and placebo, each for a 1-week period, under double-blind conditions on a research unit of a general hospital. Each patient served as his or her own control. The optimal dose of physostigmine for each patient was determined previously by a dose-finding phase. There were no significant group differences on a number of neuropsychological tests. Along with other studies in the literature, this study casts serious doubt on the efficacy of short-term administration of oral physostigmine when used alone in an attempt to ameliorate cognitive dysfunction in Alzheimer's disease patients. The possibilities that physostigmine may slow the course of the disease or may acutely improve symptoms when combined with other agents are discussed.", "Owing to the pharmacokinetic properties of physostigmine when administered by conventional routes, long-term cholinergic treatment of Alzheimer's disease is difficult to manage. In order to overcome the problems associated with the oral and intravenous application of physostigmine, and to improve patients' compliance, a transdermal therapeutic system was developed. The efficacy and tolerability of this system were evaluated in a double-blind, randomized, multicenter study comparing patches containing 30 mg and 60 mg physostigmine with a placebo patch. The clinical trial followed the basic principles of the various guidelines on the evaluation of anti-dementia drugs, and included patients with mild to moderate probable Alzheimer's disease. A total of 204 patients with probable Alzheimer's disease were included in the study. Of these, 136 patients were eligible for the according-to-protocol analysis of efficacy, 167 subjects for the intention-to-treat analysis of efficacy, and 181 patients were included in the safety analysis. In contrast to the hypothesis to be tested, the efficacy of physostigmine was not superior to that of placebo after a treatment period of 24 weeks. On the contrary, there was even a slight, but not statistically significant, trend toward a better outcome in the placebo group. Median physostigmine plasma concentrations of approximately 100 pg/ml were measured, showing a high degree of interindividual variability and no linear dose relationship between the 30 mg and 60 mg dosages. Plasma cholinesterase activity was not significantly affected by physostigmine. The physostigmine patch application in doses of 30 mg and 60 mg apparently did not lead to physostigmine plasma concentrations that were sufficient to compensate for cholinergic deficiencies in affected brain areas and produce clinical benefits. Both the drug and the transdermal system were generally well tolerated under the study conditions. Modifications of the patch system may perhaps make it possible to achieve higher physostigmine plasma concentrations, which seem to be required to induce the expected beneficial effects during long-term treatment of Alzheimer's disease.", "The efficacy of extended-release physostigmine salicylate, an acetylcholinesterase inhibitor, was evaluated in 850 subjects with mild-to-moderate Alzheimer disease (AD) in a multicenter trial.\n Subjects initially entered a dose-enrichment phase in which they received 1 week each of physostigmine salicylate, 24 mg/d and 30 mg/d, and daily placebo. Among the subjects who completed this phase, 35.9% responded to physostigmine treatment, whereas 62.4% were considered nonresponders, and 1.6% could not be evaluated because of missing data. After a 4-week placebo-washout phase, 176 responder subjects were randomized to receive their best dose of physostigmine or placebo in a 12-week double-blind phase. Primary efficacy measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC+), and the Clinical Global Impression of Change (CGIC).\n In the intent-to-treat analysis of the double-blind phase, physostigmine-treated subjects scored -2.02 points better than placebo-treated subjects on the ADAS-Cog (F1,167 = 6.42 [P = .01]) and 0.33 points higher on the CIBIC+ (F1,150 = 5.68 [P = .02]). No significant improvement was observed on the CGIC or the secondary outcome measures. Nausea and vomiting were experienced by 47.0% of all physostigmine-treated subjects during the double-blind phase.\n Physostigmine demonstrated a statistically significant benefit compared with placebo on a clinical global rating of change and an objective test of cognitive function. Given the frequency of gastrointestinal side effects, the role of this agent in clinical use remains to be determined.", "Physostigmine (.125 mg, .25 mg, or .50 mg) or placebo was administered intravenously to 10 neuroleptic-free patients with Alzheimer's disease over a 30-minute period. All patients performed better on a recognition memory task while receiving physostigmine. When placebo or the dose of physostigmine previously associated with an improvement in memory was readministered, physostigmine again enhanced performance on a recognition memory task. These results indicate that the acute augmentation of cholinergic activity in some patients with Alzheimer's disease can partially reverse the memory deficit of that disorder and may provide an approach to the eventual therapy of this condition.", "We assessed the effect of chronic long-term physostigmine in 20 patients with probable Alzheimer's disease. Initially, all patients went through a dose-finding phase and a double-blind crossover period, and were subsequently classified as physostigmine responders or nonresponders based on an a priori classification system. We then offered all patients long-term treatment with physostigmine regardless of their initial classification. Results revealed that responders spent significantly (p less than 0.0005) longer time periods on drug (36.1 +/- 4.6 months) than nonresponders (10.8 +/- 3.2). During a 2nd crossover period, 18 months into treatment, responders still demonstrated behavioral improvement, as assessed with the Sandoz Clinical Assessment-Geriatric Scale, whereas there were no behavioral changes observed in nonresponders. There were no effects on formal neuropsychological assessment. The results suggest that a subgroup of Alzheimer's patients benefits from long-term physostigmine therapy.", "To study the pharmacokinetic and pharmacodynamic properties of physostigmine in subjects with Alzheimer's disease.\n Plasma physostigmine concentration and butyrylcholinesterase inhibition were measured in blood samples collected during and after a single high-dose (1 to 1.5 mg for 45 to 60 minutes) and a sustained low-dose steady-state intravenous infusion in nine subjects with Alzheimer's disease. Escalating doses (0.5 to 25 mg/day) were administered during a 2-week period. A dose (2 to 12 mg/day) that optimized cognition in each subject was identified and then administered in a randomized, double-blind, placebo-controlled crossover design for 1 week.\n The elimination half-life of physostigmine was 16.4 +/- 3.2 (SE) minutes. Clearance and volume of distribution were 7.7 +/- 0.9 (SE) L/min and 2.4 +/- 0.6 (SE) L/kg, respectively. Butyrylcholinesterase inhibition half-life was 83.7 +/- 5.2 (SE) minutes. During sustained steady-state infusion, plasma physostigmine concentration (r = 0.95) and butyrylcholinesterase inhibition (r = 0.99) were linearly correlated with the dose. In five cognitive responders, the memory enhancement was significantly correlated (r = 0.86; p < 0.05) with butyrylcholinesterase inhibition.\n These results showed that, in cognitive responders, memory enhancement by physostigmine in Alzheimer's disease is correlated directly to the magnitude of plasma cholinesterase inhibition. Furthermore, during single-dose conditions, the dynamic half-life is five-fold longer than the kinetic half-life." ]

[ "3690941", "2197381", "7021431", "3792434", "6368614", "3365916", "6763202", "6392354", "8387662", "6354602", "3540871", "6359083", "3326676", "6991540", "6371063", "3287907", "3311548", "3540870" ]

[ "The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain.", "Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars.", "Propiram and codeine in episiotomy pain.", "Double-blind comparison of the analgesic potency of ciramadol, codeine and placebo against postsurgical pain in ambulant patients.", "The relative analgesic efficacy of propiram fumarate, codeine, aspirin, and placebo in post-impaction dental pain.", "A double-blind study of diflunisal and codeine compared with codeine or diflunisal alone in postoperative pain.", "Analgesic efficacy of an ibuprofen-codeine combination.", "Double-blind parallel comparison of single oral doses of ketoprofen, codeine, and placebo in patients with moderate to severe dental pain.", "Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.", "A double-blind trial of single-dose ciramadol for the treatment of post-episiotomy pain.", "Analgesic effect of naproxen sodium, codeine, a naproxen-codeine combination and aspirin on the postoperative pain of oral surgery.", "Analgesic effects of oral propiram fumarate, codeine sulfate and placebo in postoperative pain.", "Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy.", "Comparison of zomepirac, APC with codeine, codeine and placebo in the treatment of moderate and severe postoperative pain.", "An appraisal of codeine as an analgesic: single-dose analysis.", "Analgesic efficacy of piroxicam in the treatment of postoperative pain.", "Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain.", "Analgesic efficacy of meclofenamate sodium in episiotomy pain." ]

[ "In a double-blind, randomized, single-dose trial the analgesic contribution of acetaminophen, 1000 mg, and codeine, 60 mg, was determined. The study was a 2 X 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of: 1000 mg acetaminophen, 60 mg codeine, 1000 mg acetaminophen plus 60 mg codeine, or placebo. The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant (P less than 0.05) contribution to the analgesic effectiveness of the combination on all measures of efficacy (sum of pain intensity differences, largest pain intensity difference, total pain relief, largest pain relief, and time to remedication). The incidence of adverse effects did not appear to differ among the treatments, including placebo.", "A single-dose, randomized, double-blind, parallel-treatment study was performed in 200 outpatients with acute pain caused by the surgical removal of impacted third molars. Meclofenamate 100 mg plus codeine 60 mg, meclofenamate 50 mg plus codeine 30 mg, meclofenamate 100 mg, codeine 60 mg, and placebo treatment groups were compared for sum of pain intensity differences, peak pain intensity difference, sum of pain relief scores, peak pain relief, number of observations at which pain was half relieved, overall evaluation of effectiveness, and time to remedication with a backup analgesic. Meclofenamate 100 mg plus codeine 60 mg was significantly more effective (P less than .005) than codeine 60 mg for all variables except number of observations at which pain was half relieved. Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective (P less than .005) than placebo for all variables. Eleven adverse experiences were reported in 7 patients (3.5%); the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg, in 2 treated with meclofenamate 50 mg plus codeine 30 mg, and in 1 treated with codeine 60 mg.", "To evaluate relative efficacy, safety, and time course of analgesia, propiram fumarate (50 and 100 mg), a new narcotic agonist-antagonist, was compared with codeine sulfate (60 mg) and placebo in a clinical trial with a single peroral dose, parallel, stratified, randomized, and double-blind design involving 80 hospitalized postpartum women with medium or severe episiotomy pain. Using verbal subjective reports as index of response, patients rated pain intensity and side effects at periodic interviews for 6 h. Relative efficacy findings based on peak effects and summed pain-intensity differences suggested dose-dependent analgesia with propiram and also that 60 mg codeine lay between 50 mg propiram and placebo. Moreover, after 50 or 100 mg propiram, 8 of 20 patients reported greater than 50% reduction of initial pain compared with 7 of 20 after 60 mg codeine and 2 of 20 after placebo. After each of the propiram doses, distinct analgesia began within 1/2 h and reached peak effect between 1 h (p less than 0.02) and 2 h (p less than 0.05). After f60 mg codeine, onset was slower and peak later (4 h, p less than 0.05). All three active drugs continued to act until the 5th or 6th h. Drowsiness was the only statistically significant side effect reported after propiram. These results suggest that single 50 or 100 mg doses of propiram were effective in episiotomy pain, induced stronger analgesia than 60 mg codeine, and took effect more rapidly.", "The efficacy and safety of ciramadol (Cir) as an analgesic in relieving moderate to severe pain after oral surgery has been studied in 79 patients randomly assigned to receive single oral doses of Cir 15, 30 or 60 mg, codeine 60 mg or placebo. During the 6-hour observation period, the three ciramadol-treated groups indicated greater pain relief than the codeine 60 mg or placebo groups. In general, Cir 60 mg was significantly more effective than codeine 60 mg, and all doses of Cir were superior to placebo. The proportion of patients in each Cir group reporting adverse experiences was significantly higher than in either the placebo or codeine groups. The experimental system proved very effective in demonstrating analgesic potency of Cir. The very high incidence of side-effects in the three ciramadol-treated groups makes it unfit for further clinical use in ambulant patients.", "To evaluate the analgesic efficacy of orally administered 50 mg propiram fumarate, 650 mg aspirin, 60 mg codeine phosphate, and placebo in acute post-impaction dental pain, 159 patients with moderate or severe pain were randomly allocated to the four treatments in this single-dose double-blind, stratified, parallel-group study. A research nurse questioned the patients at 1/2 hour and hourly for 6 hours after medicating. A standard format was used to question subjects about their pain intensity and relief from the starting pain. Propiram, 50 mg, produced a level of analgesia approaching that of 650 mg aspirin in peak effect, total effect, and duration of action and was statistically superior to 60 mg codeine and placebo for every measure of analgesic efficacy. Several mild adverse effects were observed; however, they appeared to be evenly distributed among the active treatments.", "A double-blind, randomized, parallel-group study compared the analgesic efficacy of a single oral dose of 500 mg diflunisal, 60 mg codeine, 500 mg diflunisal plus 60 mg codeine given as separate agents, and placebo in 161 patients with moderate to severe postoperative pain. Standard subjective measures were used to evaluate analgesia. Eight-hour sum of pain intensity differences and total pain relief scores for all active treatments were significantly better than were those for placebo (p less than 0.05). Diflunisal plus codeine performed the best followed by diflunisal, codeine, and placebo. Diflunisal plus codeine was better than placebo from 1 1/2 to 8 hours (p less than 0.01), better than codeine from 1 1/2 to 6 hours (p less than 0.05), and better than diflunisal alone from 1/2 to 1 1/2 hours (p less than 0.05) for most measures of analgesia. Factorial analysis demonstrated a significant early codeine effect and a significant diflunisal effect throughout. No significant treatment group differences were observed regarding adverse effects. Our data demonstrate that diflunisal plus codeine is generally well tolerated and provides analgesia superior to that of diflunisal or codeine alone in the treatment of moderate to severe postoperative pain.", "Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given, under double-blind, randomized conditions, a single dose of either codeine 60 mg, aspirin 650 mg, ibuprofen 400 mg, aspirin 650 mg + codeine 60 mg, ibuprofen 400 mg + codeine 60 mg, or placebo. A total of 249 subjects were included in the statistical analysis. On a report form, subjects recorded pain intensity, pain relief, and side effects hourly for four hours. They also gave an overall impression at the end of the observation period. Analysis of variance and pairwise contrasts were used to analyze the data. For the sum of pain intensity differences, the total of the hourly pain relief scores, and overall impression, there was a significant analgesic effect for codeine, aspirin, and ibuprofen and no significant interaction when they were used in combination. Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination. The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter, but it was not statistically superior to ibuprofen alone. The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model. There was no notable difference in the frequency or intensity of side effects among the treatment groups, and no subject had to withdraw due to an adverse effect. This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination. Codeine added a small amount of additional analgesia when used in combination with ibuprofen.", "Ketoprofen, 25, 50, and 100 mg, was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth. Treatment was self-administered as a single oral dose under double-blind conditions in five parallel groups established by a random code in healthy young adults. Based on 129 patient evaluations of pain experience and pain relief, ketoprofen was shown to have a more rapid onset and longer duration of action than codeine. In the derived variables of SPID (Sum of Pain Intensity Differences) and TOPAR (Total Pain Relief), all three doses of ketoprofen, with no dose-related differences among them, were found to provide statistically superior analgesia to codeine and placebo. All five treatments were associated with some adverse reactions.", "The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.", "A randomized double-blind trial was carried out in 54 women to evaluate the effectiveness of ciramadol in a single (60 or 30 mg) oral dose regimen, compared with 60 mg codeine and placebo, in the treatment of post-episiotomy pain. Ciramadol gave a significantly better analgesic effect, at both 2 and 6 hours, and produced negligible side-effects. Codeine did less well than placebo in this study.", "In a double-blind study, 198 outpatients with pain after oral surgery were randomly assigned to treatment with a single oral dose of naproxen sodium 550 mg, codeine sulfate 60 mg, a combination of naproxen sodium 550 mg with codeine sulfate 60 mg, aspirin 650 mg or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia; the codeine effect was significant for total and peak pain relief and patients' overall evaluation. The naproxen-codeine interaction was not statistically significant for any measure, which suggests that the analgesic effect of the combination represents the additive effect of its constituents. Based on pairwise comparisons, aspirin was significantly superior to placebo for most measures of effect, naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients' overall evaluation. No more patients experienced adverse effects with aspirin or naproxen than with placebo, but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen.", "Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of propiram fumarate 50 mg, codeine sulfate 60 mg and placebo in the relief of moderate to severe postoperative pain. One hundred and twenty patients completed a randomized, double-blind, single-dose, stratified, parallel-groups trial and were observed for either 4 or 6 hours. Based upon each of the summary efficacy measures--SPID, % SPID and TOTAL--propiram and codeine were approximately equally effective and both were statistically superior to placebo. Propiram was significantly more effective than codeine at hour 5 for Pain Intensity Difference. Two adverse effects were attributed to propiram. Propiram fumarate 50 mg is an effective oral analgesic similar to codeine sulfate 60 mg, with the possibility of a longer duration of action.", "Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain.", "nan", "Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.", "Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain.", "Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents.", "Meclofenamate sodium was compared, double-blind, with codeine and placebo for the treatment of acute episiotomy pain. One hundred sixty-eight women with moderate or severe episiotomy pain after normal delivery were assigned randomly to one of four treatment groups: one received meclofenamate sodium 200 mg at dose 1 and 100 mg at doses 2 and 3; one received meclofenamate sodium 100 mg at dose 1 and 50 mg at doses 2 and 3; one received codeine 60 mg at all three doses; and one received placebo at all three doses. Efficacy measurements were evaluated periodically for 6 hours after medication. After the first administration, both doses of meclofenamate sodium were significantly superior to placebo and to codeine from 2-6 hours in pain intensity difference and pain relief. For second and third doses, data were available for too few patients to allow valid analysis and interpretation. Adverse effects occurred in 4 patients in each meclofenamate sodium group, and in 8 in the codeine group and in 6 in the placebo group. The study indicates that single 100- and 200-mg doses of meclofenamate sodium are as safe as, and significantly more effective than, codeine 60 mg or placebo for episiotomy pain." ]

[ "14597516", "6870623", "769560", "2023746", "9098257", "12635675", "4289281", "3951807", "6353843", "4429308", "4728562", "9951493", "7211267", "5307565", "5054238", "3237131", "9298049", "7352858", "3813951", "3288070", "3317180" ]

[ "A phase III, multicenter, randomized, placebo-controlled clinical trial of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.", "Aminocaproic acid decreases secondary hemorrhage after traumatic hyphema.", "Aminocaproic acid in the treatment of traumatic hyphema.", "Aminocaproic acid versus prednisone for the treatment of traumatic hyphema. A randomized clinical trial.", "Clinical evaluation of aminocaproic acid for managing traumatic hyphema in children.", "Topical aminocaproic acid to prevent rebleeding in cases of traumatic hyphema.", "Traumatic hyphema: its clinical characteristics and failure of estrogens to alter its course. A double-blind study.", "A comparison of two dose regimens of epsilon aminocaproic acid in the prevention and management of secondary traumatic hyphemas.", "Tranexamic acid and traumatic hyphaema. A prospective study.", "The management of traumatic hyphema.", "Monocular versus binocular patching in traumatic hyphema.", "Comparison of tranexamic acid and prednisolone in the treatment of traumatic hyphema. A randomized clinical trial.", "The effect of tranexamic acid on secondary haemorrhage after traumatic hyphaema.", "The treatment of contusion of the eye.", "Traumatic hyphema.", "The role of tranexamic acid (Cyklokapron) in the treatment of traumatic hyphaema.", "Topical aminocaproic acid in the treatment of traumatic hyphema.", "Traumatic hyphema. Failure of steroids to alter its course: a double-blind prospective study.", "Aminocaproic acid reduces the risk of secondary hemorrhage in patients with traumatic hyphema.", "Aspirin and secondary bleeding after traumatic hyphema.", "Traumatic hyphema in children. Treatment with epsilon-aminocaproic acid." ]

[ "To determine the safety and efficacy of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.\n Multicenter, randomized, double-masked, placebo-controlled clinical trial.\n A total of 51 patients participated in this trial (power = 36%, 2-tailed test).\n Patients presenting with traumatic hyphema were randomly assigned to 5-day treatment with topical aminocaproic acid or a placebo gel. Patients were monitored daily with ocular examination and vital sign testing for the 5 days of treatment and at 24 and 48 hours after treatment. General physical examination and laboratory testing were performed at baseline and day 5.\n The main efficacy variable was the rate of rebleeding. Secondary efficacy variables included time to hyphema clearance, intraocular pressure, time to secondary hemorrhage, and visual acuity. Safety variables included adverse events, vital signs, and laboratory measurements.\n Rebleeding occurred in 30% of the placebo group (8 of 27; 95% confidence interval [CI] = 14-50%), versus 8% of the treatment group (2 of 24; 95% CI = 1-27%), for an estimated continuity-corrected difference in percentage of patients with bleeding of 17% (95% CI = -3-38%). Secondary efficacy variables were similar in the groups, except that there was a trend towards more visual improvement in the topical aminocaproic acid group (54%) than in the placebo group (30%) at the last measurement (P = 0.08). Adverse events were similar.\n This study provides evidence that topical aminocaproic acid is safe and demonstrates trends towards reducing the rebleeding rate in the management of traumatic hyphema. However, because the study was terminated before complete enrollment, more definitive recommendations will require a larger trial.", "Forty-eight patients (49 eyes) had nonperforating traumatic hyphema. Twenty-eight patients (28 eyes with hyphema) received oral aminocaproic acid, an antifibrinolytic agent, in a dosage of 100 mg/kg every four hours for five days, up to a maximum daily dose of 30 g. Twenty patients (21 eyes with hyphema) received placebo in an identical regimen. One eye treated with aminocaproic acid rebled; seven eyes receiving the placebo rebled. The results of this study show a statistically significant reduction in the incidence of secondary hemorrhage in the patients receiving aminocaproic acid.", "Of 59 patients with traumatic hyphema studied prospectively, 32 received aminocaproic acid, an antifibrinolytic agent, to prevent secondary hemorrhage. The remaining 27 patients received placebo in an identical manner. Of the aminocaproic acid-treated patients, only one (3%) rebled, while nine patients (33%) receiving placebo suffered secondary hemorrhage. The results of this study indicate a statistically significant reduction (P less than .01) in the incidence of rebleeding in patients treated with this drug.", "One hundred twelve patients who sustained hyphema after blunt trauma were enrolled in a double-blind randomized clinical trial to determine the relative efficacies of aminocaproic acid (Amicar) and systemic prednisone for reducing the rate of secondary hemorrhage. Fifty-six patients received an oral dosage of 50 mg/kg of aminocaproic acid every 4 hours for 5 days, up to a maximum of 30 g daily, and 56 patients received an oral dosage of 40 mg of prednisone daily (adjusted for weight) in two divided doses. Placebo pills and liquids were given to each patient to mask the treatment schedules. There were no statistically significant differences between the patient populations for any demographic or clinical characteristic (e.g., visual acuity, intraocular pressure [IOP], initial hyphema size) measured in the study. Blacks comprised 53% of the study population, and the mean age of the patients was 23.5 years. Four patients in each of the treatment groups experienced a secondary hemorrhage; the rebleed rate was 7.1% in each group.", "The purpose of this study is to determine the incidence of secondary hemorrhage after traumatic hyphema in children and to evaluate the efficacy of epsilon aminocaproic acid in reducing this incidence.\n In a prospective, randomized, double-blind study performed between November 1987 and February 1994, 94 children admitted for traumatic hyphema were assigned to receive either aminocaproic acid (n = 48) (100 mg/kg every 4 hours; maximum, 30 g daily) or placebo (n = 46) for 5 days. Patients who had ingested aspirin in the week preceding admission were excluded from the study.\n Mean age of the patients was 9.4 years. Black patients comprised 4% of the study population. Secondary hemorrhage occurred in only three patients (3.2%), two from the placebo group and one from the aminocaproic acid group, none of whom had any complications. The duration of hospital stay and the clot resorption times were increased significantly in the aminocaproic acid group (P < 0.001).\n The authors report a very low incidence of secondary hemorrhage compared with most previous studies. This difference is likely related to the small proportion of black patients in our study and to the exclusion of patients having ingested aspirin, two factors that seem to be associated with higher rates of rebleeding. The efficacy of aminocaproic acid could not be determined due to the low incidence of hemorrhage. The results of this study, however, suggest that the incidence of secondary hemorrhage in white patients without prior ingestion of aspirin is insufficient to justify routine use of aminocaproic acid in managing traumatic hyphema. Rather, an individualized decision based on the risk factors of each patient would seem more appropriate to avoid a slower clot resorption time and possible side effects of this medication.", "To determine the effect of topical aminocaproic acid on the incidence of rebleeding after traumatic hyphema.\n This randomized double blind clinical trial investigated 132 consecutive cases of traumatic hyphema referred to the emergency room of Farabi Eye Hospital in 1998-1999. The patients were randomly divided into three groups: Group 1 received cycloplegic drops only. Group 2 received cycloplegic drops and 2% carboxy polymethylene (CPM) gel as placebo. Group 3 was treated with cycloplegic drops and 25% aminocaproic acid (ACA) in CPM gel (supplied by Messrs. Sina Darou). All patients were treated for five days on an outpatient basis, with a two-week follow-up. The incidence of rebleeding, time needed for clot absorption, and complications of hyphema were recorded and analyzed using the chi-square and Student's t-tests and logistic regression modeling.\n Rebleeding occurred in 8 eyes of 52 patients in group 1 (15.4%), 7 eyes of the 39 patients in group 2 (17.9%) and 5 eyes of the 41 patients in group 3 (12.2%). This difference was not significant. The time needed for clot absorption in groups 1, 2 and 3 was respectively 9.5 +/- 3.9, 9.3 +/- 4.2 and 11.15 +/- 4.7 days, the difference between group 3 and the other two groups being statistically significant (p<0.04).\n Topical 25% ACA is not effective in reducing the incidence of rebleeding and lengthens the time needed for clot absorption.", "nan", "Fifty-nine patients who sustained hyphema following blunt trauma were randomly assigned prospectively to either of two dose regimens of epsilon aminocaproic acid (Amicar). Twenty-six took an oral dosage of 50 mg/kg (\"half dose\") every four hours for five days, up to a maximum of 30 g/day, and 33 patients received 100 mg/kg (\"full-dose\") every four hours up to a maximum of 30 g/day. Five patients in the full-dose group experienced dizziness, hypotension, and syncope. Half-dose Amicar substantially reduced such serious side effects (P = 0.063), had no adverse effect on the reduced rate of recurrent hemorrhages (P = 0.22), and was more cost effective than the full-dose regimen. When the two patients in the half-dose group receiving 30 g/day of Amicar were deleted, however, the comparison of dizziness and hypotension in the two groups became more significant (P = 0.050). The incidence of nausea and vomiting was approximately the same in both groups (P = 0.52). Serum Amicar levels were within the range of plasminogen inhibition at both dose levels. Prior aspirin ingestion appeared to have no influence on the rate of rebleeding (P = 0.58).", "112 patients with traumatic hyphaema were investigated prospectively over a period of 3 years. 53 had conservative treatment and 59 tranexamic acid treatment. They were hospitalized, but fully mobilized. Both groups were given supplementary local therapy with glucocorticoids and mydriatics as well as monocular patching. In neither group was any re-bleeding seen. The resorption of blood was delayed in the tranexamic treated patients, which may be taken as indirect proof of the efficacy of the treatment. The longer persistence of blood in the anterior chamber in the tranexamic acid treated group caused no complication. The treatment was well tolerated. In both departments treatment with tranexamic acid had replaced the bed rest treatment.", "nan", "nan", "Oral antifibrinolytics, oral steroids, and no oral treatment are the preferred medical treatments for traumatic hyphema. Antifibrinolytics and steroids have decreased the chance of rebleeding in some studies but failed to alter the clinical course in others. Rate of secondary hemorrhage seems variable among different geographic and ethnic groups of patients. Comparison of the treatments in each population is necessary to document the most effective method of preventing recurrent hemorrhage.\n Randomized, placebo-controlled, clinical trial.\n Two hundred thirty-eight patients in whom hyphema developed after a blunt trauma entered the study.\n Eighty patients received 75 mg/kg per day oral tranexamic acid (TA) divided into 3 doses, 80 patients received a placebo with the same number of tablets and frequency as those of the TA group, and 78 patients received 0.75 mg/kg per day oral prednisolone divided into 2 doses.\n Secondary hemorrhage during the hospital course was measured.\n Secondary hemorrhage occurred in 8 patients (10%) of the TA group, 14 patients (18%) of the prednisolone group, and 21 patients (26%) of the placebo group. The difference between the incidence of rebleeding between TA and placebo groups was statistically significant (P = 0.008). Patients receiving a placebo had a greater chance of secondary bleeding than did patients receiving TA (odds ratios = 3.2; 95% confidence interval = 1.3, 7.5). The incidences of rebleeding were not significantly different in placebo versus prednisolone groups (P = 0.21) and TA versus prednisolone groups (P = 0.15).\n In a population with a high rate of secondary bleeding, TA is more effective than oral prednisolone or no oral treatment in preventing rebleeding among patients with traumatic hyphema.", "During the period from March 1978 to November 1979, 232 consecutive patients with traumatic hyphaema were allocated by admission-date to conservative treatment and to treatment with the antifibrinolytic drug tranexamic acid. Secondary haemorrhage occurred in only two of 102 tranexamic acid treated patients, while secondary haemorrhage occurred in 12 out of 130 conservatively treated patients. This difference was statistically significant. Some clinical aspects of the rebleeding cases are presented and briefly discussed.", "nan", "nan", "nan", "To determine whether topically applied aminocaproic acid, like systemic aminocaproic acid, effectively reduces secondary hemorrhage after hyphemas and to compare the safety and effectiveness of topical application with those of systemic use and a control group.\n A prospective, randomized, double-masked, multicenter study.\n Sixty-four patients with traumatic hyphema treated with topical or systemic aminocaproic acid and compared with 54 control patients with hyphema. Daily slitlamp examinations for hyphema grading and corneal clarity, initial and final visual acuity, applanation tonometry, and fundus indirect ophthalmoscopy were studied. Follow-up was 6 months to 5 1/2 years (mean, 2.96 years).\n Compared with the control group, topical and systemic aminocaproic acid was statistically significant in preventing secondary hemorrhage. Only 3% (2/64) of the patients who received topical or systemic aminocaproic acid had secondary hemorrhage compared with 22% (12/54) of the control group (P = .002). Final visual acuity was 20/40 or better in 30 patients (86%) in the topical group compared with 23 patients (43%) in the control group (P < .001). Final visual acuity was 20/40 or better in 20 patients (69%) in the systemic aminocaproic acid group compared with 23 patients (43%) in the control group (P = .04). The topical aminocaproic acid group had a final visual acuity of 20/40 or better in 86% of patients, compared with 69% of patients in the systemic group.\n Topical aminocaproic acid appears to be a safe, effective treatment to prevent secondary hemorrhage in traumatic hyphema. It is as effective as systemic aminocaproic acid in reducing secondary hemorrhage. No systemic side effects were observed with topical use. Topical aminocaproic acid provides an effective out-patient treatment for traumatic hyphemas.", "Forty-three patients with traumatic hypema were studied prospectively in a controlled, double-blind study. Twenty-three patients received prednisone and 20 received a lactose placebo. Secondary hemorrhages occurred in 16% of all patients. There was no significant difference in the incidence of secondary hemorrhage between the two groups (P = .85). There is no evidence that prednisone (40 mg/day) decreases the incidence of secondary hemorrhage. There was no significant difference in final visual acuities between the two groups. Patients with initially larger hyphemas do not appear to have worse final visual acuities. Hyphemas without secondary hemorrhage had a uniformly good prognosis. Although final visual acuities were worse in eyes with secondary hemorrhage, associated ocular injuries rather than blood-related complications accounted for the decreased visual acuity.", "In a prospective, randomized, double-masked study, 34 patients (34 eyes) with nonperforating ocular injury and traumatic hyphema were treated with either aminocaproic acid (Amicar), 100 mg/kg every four hours, up to a maximum of 30 g/d, or placebo for five days. None of 21 patients who were treated with aminocaproic acid rebled, while three (23%) of 13 patients who were treated with placebo rebled. This difference was statistically significant. Of the three patients who rebled, two required surgical intervention, with one patient requiring four surgical procedures. Although complications following aminocaproic acid therapy included light-headedness, nausea and vomiting, and systemic hypotension, only one patient was withdrawn from the study because of drug-related adverse reactions. This study strongly confirms that aminocaproic acid therapy significantly reduces the incidence of secondary hemorrhage following traumatic hyphema.", "A randomized, controlled study was conducted in 51 patients to investigate the effect of aspirin administration on traumatic hyphema. Aspirin tablets 500 mg tid were administered for seven days. Rebleeding was found in three of 23 eyes of patients who had received aspirin and in two of 28 eyes of control patients. This difference was not statistically significant (P = .405), proving that aspirin is not an important factor in rebleeding in patients with hyphema.", "Forty-nine patients, ages 3 to 18 years, who sustained nonpenetrating unilateral trauma with hyphemas were assigned randomly to receive either 100 mg/kg of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, orally every 4 hours for 5 days (maximum 30 g/day) or a placebo. No patients ingested acetylsalicylic acid (ASA)-containing compounds before or during admission. Two patients of 24 treated with EACA and 1 of 25 given placebo had rebleeds. The hyphemas in the EACA-treated group took significantly longer to clear (mean, 5.3 versus 2.6 days; P less than 0.001). Because of the low incidence of rebleeds in the placebo group, the efficacy of EACA in reducing the rate of rebleeds could not be determined. Further studies with this drug, controlling for age, race, sickle trait, and pre-admission antiplatelet agents should be undertaken before its routine use in traumatic hyphema management can be recommended." ]

[ "8927680", "2570438", "9131723", "1683334", "2883680", "1683336", "1352521", "15551193" ]

[ "A comparison of an atypical and typical antipsychotic, zotepine versus haloperidol in patients with acute exacerbation of schizophrenia: a parallel-group double-blind trial.", "Zotepine vs. haloperidol in paranoid schizophrenia: a double-blind trial.", "Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.", "[Effectiveness and tolerance of zotepine in a double-blind comparison with perazine in schizophrenic patients].", "Comparison of efficacy of zotepine and thiothixene in schizophrenia in a double-blind study.", "[Zotepine versus perazine in patients with paranoid schizophrenia: a double-blind controlled trial of its effectiveness].", "Zotepine in the treatment of schizophrenic patients with prevailingly negative symptoms. A double-blind trial vs. haloperidol.", "Zotepine versus placebo in the treatment of schizophrenic patients with stable primary negative symptoms: a randomized double-blind multicenter trial." ]

[ "The atypical antipsychotic zotepine was compared to haloperidol in 126 patients suffering from acute exacerbation of schizophrenia (DSM-III-R) in a randomized, double-blind study. After 8-weeks, 150 to 300 mg zotepine improved scores on the Brief Psychiatric Rating Scale (BPRS) more than 10 to 20 mg haloperidol (-17.03 versus -13.45; 95%CI for zotepine-haloperidol -9.34/2.04). BPRS subscores and Clinical Global impressions (CGI) Severity and improvement subscales showed comparable gains, but scores on the Scale for the Assessment of Negative Symptoms (SANS) improved significantly more with zotepine (-23.82) than haloperidol (-15.15; P < .05; 95%CI for zotepine haloperidol -18.03/-0.18). Adverse events were reported by 71 percent of zotepine and 78 percent of haloperidol patients. Extrapyramidal side effect (EPMS) scores decreased with zotepine (-0.34) but increased with haloperidol (+2.32; P < .05). Seven haloperidol patients reported akathisia but no zotepine patients did (p < .05). Uric acid reductions (which appear to have no clinical consequence) and transient raised liver enzymes were recorded with zotepine. Weight increased on zotepine (2.32 kg; P < .001) and a small increase in pulse rate occurred (P < .05). Both drugs were effective in reducing positive symptoms of schizophrenia; zotepine was significantly more effective against negative symptoms and reduced EPMS.", "nan", "Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a \"trait\" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.", "40 inpatients suffering from a schizophrenia (ICD-9) were treated with either zotepine or perazin. The study was continued for a period of 28 days. Assessment of clinical efficacy was effected via BPRS, AMDP, CGI and SANS; tolerance was assessed by means of Simpson's scale. In addition, EEG, ECG and laboratory controls were conducted. The overall therapeutic efficacy was good, and it was not possible to distinguish one group from the other, i.e. both substances were equally effective, judged by means of the psychopathometric tools that were at our disposal. In 11 patients of the zotepine group and in 9 patients of the perazin group, slight extrapyramidal symptoms were observed. No clinically relevant changes were seen in EEG, ECG and laboratory controls in both groups.", "Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial. Using overall improvement ratings and Gorham's BPRS, zotepine rated higher improvement in motor retardation, suspiciousness, mannerisms and posturing symptoms, suggesting that it has both activating and antipsychotic activities. Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior, somatic concerns, anxiety, guilt feelings, tension, depressive mood and uncooperativeness. As for side effects, there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene. The lower incidence of insomnia is interesting in view of zotepine's clinical activating effects. There were no abnormal laboratory findings.", "The dibenzothiepine zotepine is a new potential \"atypical\" neuroleptic exhibiting powerful antiserotonergic and antidopaminergic properties. The efficacy of zotepine was evaluated in a double-blind controlled trial versus the tricyclic neuroleptic perazine in 41 patients suffering mainly from the paranoid-hallucinatory type of schizophrenia. The key outcome variable was the extent of mental disturbance as defined by the total score of the BPRS. Additional outcome variables were GAS and CGI. In addition, adverse reactions and extrapyramidal side effects were assessed according to the FSUCL scale and the Gerlach and AIMS rating scale, respectively. Additional variables recorded were blood pressure, heart rate and routine laboratory parameters as well as electrocardiogram and electroencephalogram. In the first two days, standard equivalent doses of both drugs were administered. Thereafter, doses were administered as required. The efficacy of both substances was compared after 7, 14 and 28 days of treatment. Both drugs showed a similar antipsychotic efficacy. Under zotepine treatment a 55% improvement of the BPRS total score was observed while perazine led to a 41% BPRS score reduction. After 7 days the zotepine group was significantly more improved than the perazine group, possibly due to a dosing effect in the perazine group. In the zotepine group, fewer adverse reactions and a better benefit/risk index were observed although the differences between the two treatment groups did not reach levels of statistical significance. There were no drug-specific abnormal laboratory findings. Thus, in the present study there was no significant difference between zotepine and perazine with respect to antipsychotic efficacy and side-effect rates. However, zotepine showed a trend to a better benefit/risk index at the end of treatment.", "Zotepine, a neuroleptic agent with additional 5-HT2 blocking properties, was compared with haloperidol in the treatment of schizophrenic patients with predominantly negative symptoms using a double-blind design. During the investigation period zotepine treated patients showed significant improvements in all rating instruments whereas haloperidol treated patients did not. Patients in the zotepine group developed fewer clinical side effects. The results of the presented study confirm the positive impressions gained in earlier open trials with zotepine.", "In contrast to traditional antipsychotic medication, newer, the so called atypical antipsychotic drugs promise to reduce primary negative symptoms in both, acute and chronic schizophrenia and improve quality of life. Zotepine, a D (2)5HT (2A) antagonist, was compared to placebo in this clinical trial to address these issues.\n In an adaptive, 8-week multicenter, double-blind, randomized, parallel group study, efficacy and tolerability as well as influence on quality of life of zotepine and placebo were compared in 80 schizophrenic patients (53 % males, age 41 +/- 11 years) who experienced stable primary negative symptoms. Efficacy was assessed using the PANSS (primary outcome criterion: PANSS negative score), CGI, and MADRS; safety was controlled by EPS (Simpson-Angus Scale), TDRS and adverse events. Quality of life was evaluated with the SF-36 health questionnaire.\n After eight weeks of treatment with an average dose of 131 +/- 49 mg/day of zotepine, no superior efficacy of zotepine compared to placebo with respect to the PANSS subscale \"negative symptoms could be demonstrated. Although patients receiving zotepine showed a pronounced reduction (per protocol set: -7.8 +/- 5.8) during treatment, it was not statistically different from a marked placebo response (-6.5 +/- 5.8). Similar small but not significant differences between zotepine and placebo were found in other subscales of the PANSS, the CGI and the MADRS. With regards to the quality of life assessment, patients under zotepine showed better results in the physical component scale and psychological well-being scale. In general, zotepine was well tolerated and there was no excess of extrapyramidal symptoms compared to placebo.\n Zotepine was not superior to placebo in reducing the severity of stable primary negative symptoms in schizophrenic patients in this trial. The main reasons for this finding were a high placebo response in a selected population, a probably too low dose of zotepine, and a short study period. However, several findings show clinical benefit of zotepine therapy in efficacy and quality of life." ]

[ "2152297", "1535229", "6139668", "7975854", "2969825", "2522147", "7483798", "9651632", "1826567", "6755247", "2141247", "1836918", "10782589", "6233921", "6110088", "9394531", "9040320", "1533478", "1535653", "2144391", "11427285" ]

[ "[Safety and immunogenicity of an anti-hepatitis-B vaccine obtained using the recombinant DNA technique: results of a longitudinal study in hospital personnel].", "Long-term follow-up of hepatitis B vaccination in susceptible hospital personnel.", "Efficacy of heat-inactivated hepatitis B vaccine in haemodialysis patients and staff. Double-blind placebo-controlled trial.", "Influence of smoking on immunological responses to hepatitis B vaccine.", "Immune response to hepatitis B vaccine given at different injection sites and by different routes: a controlled randomized study.", "Low-dose (2 micrograms) hepatitis B vaccination in medical students: comparable immunogenicity for intramuscular and intradermal routes.", "Comparison of three different schedules of vaccination against hepatitis B in health care workers.", "Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational risk of hepatitis B virus infection.", "Immunogenicity of low-dose intradermal recombinant DNA hepatitis B vaccine.", "Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection.", "A randomized double-blind clinical trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine compared with a plasma-derived vaccine.", "Intradermal hepatitis B vaccination in a large hospital employee population.", "Comparison of higher-dose intradermal hepatitis B vaccination to standard intramuscular vaccination of healthcare workers.", "Hepatitis B vaccine in health care personnel: safety, immunogenicity, and indicators of efficacy.", "Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in French haemodialysis units: I, Medical staff.", "Immunogenicity of low-dose intramuscular and intradermal vaccination with recombinant hepatitis B vaccine.", "Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.", "Clinical evaluation of low dose intradermally administered hepatitis B vaccine: a comparison of plasma-derived and recombinant yeast-derived vaccines.", "Low-cost hepatitis B vaccine improves uptake among self-paying health-care students.", "Intradermal and intramuscular route for vaccination against hepatitis B.", "Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers." ]

[ "A prospective study of the immunogenicity, safety and persistence of antibodies induced by the DNA-recombinant anti-hepatitis B vaccine Engerix B was conducted in a risk group as health care workers. 115 health care workers were randomly allocated into two groups. Immunization was carried out according to a 0-1-6 month vaccination schedule in one group and to a 0-1-2-12 month schedule in the other group. Results indicate that the DNA-recombinant anti-hepatitis B vaccine is well tolerated and highly immunogenic. Reactogenicity to the vaccine was low in incidence and mild in severity with no significant difference appearing between the study groups.", "Two hundred and sixty-seven susceptible hospital personnel who had been randomly divided into three groups to receive different doses (5 micrograms, 2 micrograms or 1 microgram) of a plasma-derived hepatitis B vaccine on a four-dose schedule were investigated annually for 4 years. Of them, 251 were vaccine responders. The percentages of persistence of antibody to hepatitis B surface antigen (anti-HBs) in these 3 groups were 95.5% (84/88), 92.3% (72/78) and 95.3% (81/85), respectively (P greater than 0.05). During the follow-up period, 12 of 21 (57.1%) responders with low anti-HBs titres (10-100 miu/mL) and 3 of 48 (6.3%) responders with medium anti-HBs titres (101-1000 miu/mL) were found to be anti-HBs seronegative, while none of the 182 candidates with high anti-HBs levels (greater than 1000 miu/mL) lost their anti-HBs. The 4 year cumulative rate of natural booster in the responders was 11.6% (29/251). None of the candidates became HBsAg positive during the follow-up period. This study revealed that low dose hepatitis B vaccine can provide satisfactory immunogenic response and long-term efficacy in Chinese adults and that the persistence of immunogenicity is not related to the vaccine dose but to the candidate's own initial anti-HBs response.", "The efficacy of a heat-inactivated hepatitis B vaccine, 3 micrograms of surface antigen (HBsAg), given at 0, 1, 2, and 5 months, was evaluated in 401 haemodialysis patients in 18 centres by a placebo-controlled, double-blind, randomised trial. The attack-rate of hepatitis B virus (HBV) infections in the control group was 18% over 435 days. The protective efficacy rate of the vaccine was 78% against all HBV infections in the entire study (p = 0.00016), and 94% against HBsAg-positive hepatitis more than 3 months after day 0. Those patients in whom HBV developed showed no evidence of vaccine-acquired anti-HBs. Among 152 similarly randomised staff members receiving three monthly injections, all 5 HBsAg-positive infections occurred in the placebo group (p = 0.022). The vaccine induced anti-HBs in 88% of the patients and 100% of the staff. Immediately after the fourth injection, anti-HBs levels were as high in responding patients as in staff. There were no serious side effects. In the four-dose schedule the vaccine provides dialysis patients with protection of the same order as that given by other hepatitis B vaccines to normal subjects.", "When 115 health-care workers participated in a study that monitored their serological responses to hepatitis B vaccine at regular intervals, it was found that smoking significantly affected their antibody titre responses adversely. The study group was randomly allocated into two comparable groups that received hepatitis B vaccine either in a rapid schedule (vaccination at 0, 1, 2 and 12 months) or a standard schedule-most commonly used worldwide-(vaccination at 0, 1, and 6 months). A significantly higher proportion of smokers, in both schedules, failed to seroconvert and to achieve higher antibody levels at month 3 (p = 0.01) and at month 13 (p = 0.0003). At month 7 a similar pattern was noted in smokers following the standard vaccination schedule (p < or = 0.05), but not in those following the rapid schedule.", "Two-hundred-ninety-nine hospital workers were randomly allocated to receive MSD hepatitis B vaccine in different injection sites and by different routes (intramuscularly by gluteal or deltoid injections or subcutaneously in the arm) or Pasteur vaccine subcutaneously. Highest rates of seroconversion and highest mean anti-HB, titres were found in subjects given MSD vaccine by intramuscular injection into the deltoid muscle.", "In a randomized controlled trial, 165 healthy medical students were immunized either by the intramuscular route (IM group) or by the intradermal route (ID group) with low-dose (2 micrograms) plasma hepatitis B vaccine (HB-VAX) at months 0, 1, 2, and 6. At month 7, protective immunity (anti-HBs greater than 10 IU/l) was observed in 90% (95% confidence interval [Cl]: 84-97) of group IM and in 94% (95% Cl: 89-99) of group ID; also geometric mean titres (IM: 533 IU/l; ID:541 IU/l) were very similar at month 7. Sixty-six (IM: 29; ID: 37) of 107 vaccinees with anti-HBs less than 1,000 IU/l at month 7 received a 2 micrograms booster injection at month 12. Long-term immunity (anti-HBs greater than 1,000 IU/l) was finally observed in 58% for group IM and 66% for group ID. For low-dose hepatitis B immunization, which reduces costs to about 16%, the IM route is to be preferred in young healthy individuals in view of an ease of administration, avoidance of long-term local side effects, and the known protective immunity of intramuscularly induced anti-HBs antibodies.", "Health care workers (HCW) are a group at risk for hepatitis B virus (HBV) infection; as a result, vaccination is recommended. However, elevated cost of the vaccination schedule is one of the limiting factors to this approach. Our aim in this study was to evaluate alternative schedules for vaccination against hepatitis B, in order to obtain safe immunization with reduced costs. We studied 300 HCW, randomized to be submitted to one of three vaccination schedules against hepatitis B: Group A--three doses of 20 micrograms i.m. (n = 103); Group B--first dose i.d. (2 micrograms), second and third doses i.m. (20 micrograms) (n = 97); Group C--first and second doses i.d. (2 micrograms), third dose i.m. (20 micrograms) (n = 100). All individuals received recombinant vaccine at 0, 1 and 6 months. After the first dose, there was no difference among the three schedules, either in terms of anamnestic response or in seroconversion rate. After the second dose, there was statistical difference among the three schedules (A > B > C), in terms of seroconversion rates. After the third dose, seroconversion rates were 92.2% in Group A and 92.8% in group B; geometric mean titers (GMT) in Group B (789.6 UI l-1) were similar to group A (1248.0 UI l-1). Group C presented a seroconversion rate of 78% and a GMT of 323.0 UI l-1, both statistically inferior to other schedules. We concluded that the schedule applied in Group B had similar results when compared to schedule A, with estimated savings of 30% in vaccine costs.(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess risk factors for decreased immunogenicity among adults vaccinated with hepatitis B vaccine and to determine the importance of differences in immunogenicity between vaccines among health care workers (HCWs).\n Randomized clinical trial and decision analysis.\n HCSw.\n Development of seroprotective levels of antibody to hepatitis B surface antigen (anti-HBs) and the number of expected chronic hepatitis B virus (HBV) infections associated with lack of protection.\n Overall, 88% of HCWs developed seroprotection. Risk factors associated with failure to develop seroprotection included increasing age, obesity, smoking and male gender (P < .05). Presence of a chronic disease was associated with lack of seroprotection only among persons > or = 40 years of age (P < .05). The two vaccines studied differed in their overall seroprotection rates (90% vs. 86%; P < .05), however, this difference was restricted to persons > or = 40 years of age (87% vs. 81%; P < .01). Among HCWs > or = 40 years of age, the decision analysis found 44 (0.34/100,000 person-years) excess chronic HBV infections over the working life of the cohort associated with use of the less immunogenic vaccine compared to the other.\n He patitis B vaccines are highly immunogenic, but have decreased immunogenicity associated with increasing age, obesity, smoking, and male gender; and among older adults, the presence of a chronic disease. One of the two available vaccines is more immunogenic among older adults; however, this finding has little clinical or public health importance. Hepatitis B vaccines should be administered to persons at occupational risk for HBV infection early in their career, preferably while they are still in their training.", "Low-dose intradermal vaccination with plasma-derived hepatitis B vaccine has been shown to give high rates of seroconversion at greatly reduced vaccine cost. We report a study comparing two groups given lower doses (1.0 or 1.5 microgram) of recombinant-derived vaccine intradermally with a control group given the standard intramuscular dose. Of the 132 randomized medical students and hospital employees, 95 completed the study. Rates of seroconversion and peak antibody titers were comparable, though antibody rose more slowly and fell somewhat faster in the intradermal groups. Increasing the intradermal dose did not improve response. Most intradermal vaccinees (80%) developed small (average 2 to 3 mm) areas of local induration, which faded slowly. Low-dose intradermal vaccination with recombinant hepatitis B vaccine results in high rates of seroconversion (greater than 90% in each protocol) at a cost that will allow individual practitioners and program with limited budgets to offer vaccination.", "We evaluated the efficacy of hepatitis B vaccine (Heptavax-B) containing only the ad subtype in a randomized, placebo-controlled, double-blind trial among 865 staff members of 43 hemodialysis units in the United States. Surface antibody developed in 92.6 per cent of the subjects after two doses of vaccine and in 96 per cent after the six-month booster. The incidence of infections with hepatitis B virus (with or without hepatitis) was 9.9 per cent in placebo recipients and 2.2 per cent in vaccine recipients (P less than 0.01). The two cases of hepatitis B among vaccine recipients did not occur in subjects in whom antibody had developed. In 81 per cent of the hepatitis events, the virus was of the ay subtype. The indicence of ay virus was 8.2 per cent among placebo recipients and 1.2 per cent among vaccine recipients (P less than 0.005). We conclude that these data confirm the efficacy of the vaccine and demonstrate subtype cross-protection.", "Eight hundred volunteers from heath care and emergency fields participated in a randomized double-blind clinical trial of a new experimental mammalian cell-derived recombinant DNA hepatitis B vaccine (Betagen) compared with a licensed plasma-derived vaccine (Heptavax-B). Vaccine injections (20 micrograms) were administered intramuscularly at 0, 1, and 6 months, and sera were tested at 0, 1, 2, 3, 6, 7, and 12 months for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen. Data from 745 vaccinees (93.1%), analyzed at the 7th month of follow-up, showed no significant difference in the seroconversion rates for Betagen (94.4%) vs Heptavax-B (97.3%), but the geometric mean titer of antibody was significantly higher for Heptavax-B (11 833 mIU/L) than for Betagen (4628 mIU/mL). The antibody response of Betagen was significantly and independently related to age and sex, while that of Heptavax-B was related to age only. Reported side effects from both vaccines were minor and mild, with approximately one fourth of all vaccinees reporting at least one side effect. Vaccinees, who had a protective level of antibody at the 7th month, were tested for antibodies at the 12th month. Of those in the Betagen-vaccinated group and those in the Heptavax-B-vaccinated group, 99.0% and 100%, respectively, were still protected. There was a proportionately larger decline in the geometric mean titers of antibody to hepatitis B surface antigen for Heptavax-B than for Betagen.", "The intradermal route of hepatitis B vaccine administration has been tested in several clinical trials and has produced various degrees of immunogenicity, but usually among small groups of participants. To assess more adequately the immunogenicity of hepatitis B vaccine using the intradermal route, the Centers for Disease Control conducted a clinical trial among 425 well health-care workers in a hospital setting. Participants were randomly assigned to one of two treatment groups: those receiving a 20 micrograms intramuscular injection, and those receiving a 2 micrograms intradermal injection. Participants received the plasma-derived hepatitis B vaccine by the standard schedule at 0, 1 and 6 months, and serum samples were collected at 3, 8, 12 and 24 months after the first dose. Antibody response rates (anti-HBs titre greater than or equal to 10 sample ratio units by radioimmunoassay) for the intradermal vaccination group were consistently lower than those for the intramuscular vaccination group at each testing interval. The differences were greatest for the 3-month test and decreased over time. Geometric mean titres for anti-HBs for the intradermal group were significantly lower than those for the intramuscular group at the 8-month test point. In addition to inoculation route, factors of gender, smoking and age were found to have significant effects on immune response. The results suggest that intradermal vaccination with hepatitis B vaccine may be appropriate under certain conditions and for certain population subgroups.", "To compare the immunogenicity of hepatitis B vaccine administered via intradermal (ID) versus intramuscular (IM) route.\n Subjects chose either to specify the route of immunization or to undergo random allocation to vaccination by the ID (0.15 mL) or the IM (1.0 mL) route. Yeast-derived recombinant hepatitis B vaccine was given at 0, 30, and 180 days. Hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) were measured by microparticle enzyme immunoassay.\n 763 subjects were enrolled. Baseline screening identified 65 subjects (8%) who were positive for HBsAb or HBcAb. Vaccination was completed by 590 (85%) of 698 enrollees (370 ID, 220 IM). Seroconversion rates (geometric mean titers [GMT]>0 IU/mL HBsAb) for those vaccinated ID were 99% and 96% for screening at 9 months and 1 year post-vaccination, respectively; subjects vaccinated intramuscularly had similar rates of 95% and 96%. Seropositivity rates (GMT > or = 10 IU/mL HBsAb) showed a similar pattern, with 95%, 92%, and 73% at 9 months and 1 and 2 years, respectively, for those vaccinated ID, and 94%, 93%, and 81% for those having IM vaccination. GMT for HBsAb was significantly higher for individuals vaccinated IM than for those vaccinated ID (P<.0001). The GMT ratio for the IM and ID routes decreased over time, being 9.3 at 9 months, 7.8 at 1 year, and 5.9 at 2 years. An unanticipated side effect of intradermal vaccination was skin discoloration at injection sites, which persisted for at least 2 years postvaccination. Two thirds (112/166) of respondents reported that they would have selected the ID route despite the discoloration.\n Higher-dose ID vaccination (3 vs 1 microg per injection) uses one sixth of the dose required for standard IM vaccination. It is a cost-effective way to vaccinate populations against hepatitis B virus, but the long-term efficacy of the ID route must still be investigated.", "In a double-blind trial, we randomly assigned 1330 high-risk health care personnel to receive three 20-micrograms doses of hepatitis B vaccine or placebo. Among vaccine recipients 58% responded within 1 month and 97% within 9 months; there was no difference in immune response to the vaccine between men and women. Efficacy was evaluated after a mean follow-up of only 13.2 months, just before the vaccine was released commercially. Five hepatitis B infections were identified in placebo recipients and one in a vaccine recipient. Although the number of infections was too small to allow confident conclusions about protective efficacy of the vaccine, we saw a 67% reduction in the need for hepatitis B immune globulin after accidental hepatitis B inoculation in the vaccine group (relative risk, 5.08; 95% confidence intervals, 1.3 to 19.9). Minor side effects occurred with equal frequency after vaccine (28.7%) and placebo (27.2%) injections; no participant had a severe adverse reaction. Vaccination with the 20-micrograms hepatitis B vaccine was highly immunogenic and safe in health care workers.", "A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in staff members from forty-eight French haemodialysis units where the risk of hepatitis B was high. Of 318 subjects who completed the protocol, 164 received three monthly injections of vaccine and 154 received corresponding injections of placebo. Hepatitis B infection was observed in 3.6% of the vaccine group and 12.3% of the placebo group (p less than 0.005). The 6 infections in the vaccine group all arose within 63 days from the first injections, whereas the 19 in the placebo group arose throughout the 12 months of follow-up. The rate of side-effects after injection did not differ in the two groups. 94% of the vaccine recipients had an immune response ( greater than 10 mIU/ml in at least 5 successive specimens). 4 months after the first injection the mean + or - 2 SE peak level of anti-HBs was 2433 + or - 1077 mIU/ml.", "The study is a randomized trial using recombinant DNA vaccine to determine whether an intramuscular 10 micrograms dose or intradermal 2 micrograms induces satisfactory anti-HBs levels compared to the standard dose of intramuscular 20 micrograms. Participants were 359 healthy medical and nurse students randomly allocated to one of the three groups: Group I-IM 20 micrograms; Group II-IM 10 micrograms; Group III-ID 2 micrograms at 0, 1 and 6 months. Anti-HBs titres were measured after complete vaccine schedule by ELISA/Pasteur. Baseline variables were similar among groups and side effects were mild after any dose. Vaccines in the IM-10 micrograms group had seroconversion rate and geometric mean titre (GMT 2344 IU L-1), not significant different from the IM-20 micrograms group (GMT 4570 IU L-1). On the contrary, 21.4% of the ID-2 micrograms recipients mount antibody concentration below 10 IU L-1 and GMT of 91 IU L-1, a statistically significant difference compared with the standard schedule IM-20 micrograms (p < 0.001). A three dose regimen of half dose IM could be considered an appropriate schedule to prevent hepatitis B in young health adults which is of relevance to the expansion of hepatitis B vaccine programme.", "To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response.\n Single centre, randomised, double blind, dose-response study.\n Research vaccine evaluation centre at a teaching hospital.\n 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component.\n Each subject was randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis B vaccine two months apart.\n Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an international antibody standard.\n 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out.\n A single dose of 20 micrograms of the vaccine was as effective as two doses of either 40 micrograms or 20 micrograms of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.", "A study of the safety and immunogenicity of plasma-derived and yeast-derived recombinant hepatitis B vaccines administered by the intradermal route is reported. Three groups of medical students were inoculated intradermally at 0, 1 and 6 months with 2 micrograms of vaccine. Group 1 (n = 24) were administered plasma-derived vaccine (Green Cross HB-vaccine), group 2 (n = 21) yeast-derived recombinant vaccine (Engerix B), and group 3 (n = 13) two doses of plasma-derived vaccine with a third dose of yeast-derived vaccine. One month after administration of the third dose of vaccine, seroconversion rates in each of the three groups were 83, 100 and 92%, respectively, with anti-HBs geometric mean titres (GMT) of 329 IU l-1, 1390 IU l-1 and 1061 IU l-1. Although differences in seroconversion rates were not statistically significant, the GMT in group 1 was significantly lower than that in group 2 (p less than 0.01) and group 3 (p less than 0.05). The results presented show that intradermal administration of plasma-derived or yeast-derived vaccine, or a combination of the two, can provoke an effective immunogenic response to hepatitis B virus at approximately 10% of the cost of intramuscular vaccination. In this study administration of yeast-derived vaccine yielded better results than plasma-derived vaccine when administered by the intradermal route.", "Advisory committees recommend hepatitis B (HBV) immunization for professional and student health-care workers. However, the currently licensed vaccines are expensive, and previous surveys have shown that few students (14%) have been immunized in Canada. A low-cost immunization program was offered to health-care students in order to determine whether the effectiveness of HBV immunization could be improved by substantially reducing the vaccine cost to recipients. The immunogenicity, side effects, and 3-dose completion rate of a low-cost Korean HBV vaccine were compared with a similar U.S.-made vaccine. A total of 922 postsecondary students enrolled in 6 health-care disciplines in Ottawa, Canada were surveyed for hepatitis-B immunization status. Nonimmunized students were subsequently offered HBV vaccine at total cost of $15 (Canadian), randomly allocated to receive 3 intramuscular doses of either Korean or U.S.-made plasma-derived HBV vaccine in a double-blind fashion, surveyed about side effects, and tested for hepatitis B surface antibody seroconversion. Only 12% of the 922 surveyed students had been previously immunized when vaccine was obtainable only at high cost. However, 66% of those not immunized participated in the vaccine trial and paid the $15 fee. Hepatitis-B surface antibody seroconversion (greater than or equal to 10 sample ratio units by radioimmunoassay) occurred in 291/311 (93.6%) and 299/310 (96.5%) of recipients of 3 doses of the Korean and U.S. vaccines, respectively (P = 0.10). There were no meaningful differences in vaccine adverse effects, and 92.6% of recipients of either vaccine completed 3 doses.(ABSTRACT TRUNCATED AT 250 WORDS)", "A recombinant hepatitis B vaccine was administered to high-risk hospital personnel by intramuscular (20 micrograms) or intradermal (2 micrograms) injections for the primary immunization (n = 69) with three doses and booster immunization (n = 51) with one dose. Basic vaccination performed intramuscularly gave rise to significantly higher seroconversion levels (97.2% versus 78.1%) and geometric mean titres of antibody (1649 versus 126 IUl-1) as compared with the intradermal route. Intradermal administration did not boost antibody titres in patients previously vaccinated intradermally. Adverse reactions were not serious or severe. The intramuscular route is recommended as the procedure of choice when vaccinating against hepatitis B.", "Hepatitis B vaccination is recommended for all healthcare workers (HCW) at risk of exposure to infectious body fluids. However, the absolute duration of protection from immunization is unknown. The purpose of this randomized comparison trial was to determine how previously immunized HCW respond to different booster doses of hepatitis B vaccine.\n Adult HCW (n=59) were classified by level of hepatitis B surface antigen (anti-HBs), either <10 milli-International Units per milliliter (mIU/ml) or 10-50 mIU/ml. Participants were then randomized to receive a 2.5 or 10 microg dose of hepatitis B vaccine. Evaluation of anti-HBs levels were conducted 10 to 14 days, one month and one year postbooster.\n All participants responded to the booster dose with increased anti-HBs levels. At 14 days, mean anti-HBs levels were significantly higher for those with higher levels at baseline (P=0.004) and those receiving the 10 microg dose (P=0.016). At one month, those with higher anti-HBs levels at baseline and those receiving the 10 microg dose were significantly higher (P<0.01 for both). At one year, the increase for the higher dose was no longer statistically significant when examined by itself (P=0.081); statistical significance (P=0.021) was achieved after adjusting for anti-HBs level at baseline. For all participants, the geometric mean anti-HBs level was 2618 mIU/ml at 14 days, 2175 mIU/ml at one month and 88.9 mIU/ml at one year. At all time points the increase in anti-HBs levels represented an increase over the geometric mean baseline level of anti-HBs (7.4 mIU/ml). Hepatitis B immunized adults responded to a booster dose of hepatitis B vaccine from 3 to 13 yr postvaccination series. Data support current recommendations that immunized HCW do not require periodic antibody testing or vaccine boosters." ]

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[ "Climacteric symptoms after oral and percutaneous hormone replacement therapy.", "Combined versus sequential hormonal replacement therapy: a double-blind, placebo-controlled study on quality of life-related outcome measures.", "Is oestrogen therapy effective in the treatment of menopausal depression?", "Graded sequential therapy in the menopause: a double-blind study.", "Replacement estrogen therapy for menopausal vasomotor flushes. Comparison of quinestrol and conjugated estrogens.", "Initial 17beta-estradiol dose for treating vasomotor symptoms.", "Menopausal hot flushes: a double blind comparison of placebo, ethinyl oestradiol and norgestrel.", "Do combinations of 1 mg estradiol and low doses of NETA effectively control menopausal symptoms?", "Dose-response and withdrawal effects on climacteric symptoms after hormonal replacement therapy. A placebo-controlled therapeutic trial.", "Vaginal bleeding in postmenopausal women taking low-dose norethindrone acetate and ethinyl estradiol combinations. The FemHRT Study Investigators.", "Cardiovascular risk factors and combined estrogen-progestin replacement therapy: a placebo-controlled study with nomegestrol acetate and estradiol.", "A randomised, double-blind, cross-over study into the effect of sequential mestranol and norethisterone on climacteric symptoms and biochemical parameters.", "Effects of \"natural oestrogen\" replacement therapy on menopausal symptoms and blood clotting.", "Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females.", "Quality of life during sequential hormone replacement therapy -- a placebo-controlled study.", "A randomized, double-blind, placebo-controlled, crossover study on the effect of oral oestradiol on acute menopausal symptoms.", "[Double-blind method of the effect of menopause symptoms, lipid profile, and endometrial thickness of continuous therapy with estradiol valerate and medroxyprogesterone acetate]." ]

[ "One hundred and ten (110) healthy early post-menopausal women with mild subjective vasomotor symptoms (mean Kupperman index score 11) participated in a long-term, double-blind, placebo-controlled therapeutic trial. The effects of 2 hormone regimens were evaluated. Group I received percutaneous oestrogen therapy for 2 yr, opposed by oral micronized progesterone (200 mg) during the second year, while Group II received oral 17 beta-oestradiol valerate together with cyproterone acetate (CPA). The serum oestrogen concentrations differed markedly in the 2 treatment groups. In Group I the serum/oestrone/oestradiol ratio was 1 (comparable to the pre-menopausal value), but in group II the ratio was greater than 5. Despite the difference in the serum oestradiol and oestrone concentrations, the mean symptom scores were rapidly and similarly reduced in both treatment groups (P less than 0.001). They remained low throughout the study and were not significantly different from pre-menopausal values.", "To compare combined and sequential hormonal replacement therapies to each other as well as placebo in patients suffering from the postmenopausal syndrome. Clinical outcomes were measured concerning both the specific postmenopausal symptoms (using the Kupperman scale) and health or well-being dimensions (using subscales of the General Health Questionnaire and specific depression and anxiety scales).\n A prospective randomized double-blind study over 12 months of 105 normal early postmenopausal women in the setting of a general hospital.\n Both hormone replacement therapies were superior to placebo on the Kupperman scale (sweating, hot flushing, myalgia and vertigo). The psychic symptoms on the Kupperman scale were psychometrically invalid. However, psychic symptoms as measured by the Beck Depression Inventory and the General Health Questionnaire were significantly improved by the hormonal replacement therapies. No differences were observed when combined therapy was compared to sequential therapy.\n One-year treatment with hormonal replacement therapy is superior to placebo in measuring the somatic and psychic symptoms of the menopausal syndrome. No differences were found in this respect between combined and sequential replacement therapy.", "Fifty-five depressed menopausal patients took part in a randomized double-blind cross-over trial using ;Harmogen' (piperazine oestrone sulphate) and placebo. The Beck depression inventory, hot flush counts, and patients' subjective assessment of well-being were used to assess clinical status. Hormonal, biochemical and coagulation profiles were carried out. Hot flushes improved significantly on oestrogen compared with placebo. Depression scores and well-being showed significant and equal improvement on oestrogen and placebo. Significant improvement in flushes in patients on placebo was observed in the first half of the trial but did not occur in the second half, in patients who had previously taken oestrogen. No significant changes occurred in biochemistry. Coagulation tests showed acceleration of the prothrombin time in patients taking ;Harmogen' compared with those on placebo. Piperazine oestrone sulphate is a relatively weak but safe oestrogen preparation, effective in treatment of vasomotor symptoms but no more effective than placebo in the treatment of depression.", "nan", "Quinestrol, conjugated estrogens, or placebo was used to treat 156 patients with pernicious vasomotor instability in a prospective, double-blind, randomized, multiinvestigator trial. Vasomotor flushes were severe in approximately 80% of the cases and moderate in 20%, relatively equally distributed among the various drug groups. Both qinestrol and conjugated estrogens were significantly more effective than placebo in relieving vasomotor symptoms (by chi2 analysis, P less than or equal to 0.05). Greatest improvement was seen in the group receiving the higher once weekly quinestrol dosage of 0.2 mg followed by the group on the lower quinestrol dosage of 0.1 mg once weekly and the group on conjugated estrogens, 1.25 mg daily for 21 days on and 7 days off. No significant difference in relief of vasomotor flushes was shown between the active drug groups. No drug-related complications or side reactions of significance occurred. The results indicate that once weekly quinestrol is effective in relieving the vasomotor symptoms of the menopause. Either of two once weekly quinestrol regimens is an effective as conjugated estrogens given daily in a cyclic manner and therefore offers an alternative form of exogenous estrogen therapy.", "To compare the efficacy of different doses of 17beta-estradiol (E2) for relief of vasomotor symptoms in menopausal women.\n This was a randomized, double-masked, placebo-controlled, 12-week study in which 333 menopausal women with moderate or severe hot flushes were assigned to treatment with 0.25 mg, 0.5 mg, 1 mg, or 2 mg oral micronized 17beta-E2, or placebo. The number and severity of hot flushes were recorded daily.\n There was a significant linear correlation between increased dosage of 17beta-E2 and decreased moderate to severe hot flushes per week (P <.001). Rapid reduction in moderate to severe hot flushes was only achieved with 1 and 2 mg, showing a significant difference from placebo at week 4 (P <.05). At week 4, half the women on placebo had reduced moderate to severe hot flushes of at least 52%; the corresponding figures were 56%, 69%, 86%, and 91% for 0.25, 0.5, 1, and 2 mg, respectively. At week 12, all doses except 0.25 mg were significantly better than placebo for reducing moderate to severe hot flushes (P <.001). Although there were no significant differences, twice as many women in the 2-mg group discontinued treatment due to adverse events, compared with the placebo group.\n Oral micronized 17beta-E2 showed a dose-response effect for reducing moderate and severe hot flushes in menopausal women. 17beta-E2 1 mg appeared to be the most useful initial dose.", "A double blind crossover study was planned in order to compare the effects of oestrogen, progestogen and placebo on hot flushes. The 49 women studied had previously undergone hysterectomy and bilateral oophorectomy. The drug regimen consisted of three months each of ethinyl oestradiol 50 microgram/day, d norgestrel 250 microgram/day, a combination of these two substance (\"Nordiol\") and a placebo. The predominant reason for requesting a change of medication was intolerable hot flushes associated with placebo use. All hormonal preparations were found to be significantly more effective than placebo in reducing hot flush frequency and intensity. Oestrogen containing medications were more effective than the progestogen (norgestrel).", "This study compared two continuous-combined hormone replacement therapy (HRT) formulations, 1 mg estradiol (E2)/0.25 mg norethisterone acetate (NETA) and 1 mg E2/0.5 mg NETA, with placebo, with regard to the efficacy for vasomotor symptom relief in menopausal women.\n A total of 119 women aged 45-61 years with moderate and severe hot flushes and with amenorrhea for at least 3 months were randomly assigned to 12 weeks' treatment with 1 mg E2/0.25 mg NETA, 1 mg E2/0.5 mg NETA or placebo. The number and severity of hot flushes, as well as any vaginal bleeding, were recorded on a daily basis. The Kupperman Menopausal Index, Greene Climacteric Scale and visual analog scales for various symptoms were assessed before and after treatment. Subpopulation analysis according to menopausal status was performed.\n Both combinations significantly reduced the number and severity of hot flushes, compared to placebo. A reduction of approximately 85% in vasomotor symptomatology occurred in the two combination groups by week 4 of treatment, and this was further diminished throughout the study to approximately 97% reduction by week 12. At the end of the study, 85% of the women receiving 1 mg E2/0.5 mg NETA and 71% of the women receiving 1 mg E2/0.25 mg NETA were considered to the clinically adequate responders to treatment. Both combinations were associated with significant improvements, compared to placebo, in visual analog scales for overall general condition, Kupperman Menopausal Index, and Greene Climacteric vasomotor and psychological subscales. While both combinations resulted in similar bleeding profiles in postmenopausal women, the combination of 1 mg E2/0.5 mg NETA resulted in the lowest incidence of bleeding in late perimenopausal women.\n The combinations of 1 mg E2/0.25 mg NETA and 1 mg E2/0.5 mg NETA rapidly relieve vasomotor symptoms and are efficacious in the majority of menopausal women, including those with severe hot flushes.", "Out of a sample of 162 early post-menopausal women, aged 45-54 yr, 131 completed a placebo-controlled study to investigate the effect of sex hormones on mild climacteric symptoms with special reference to the dose-response relationship and withdrawal effects. The women were followed up for 42 mth under four different study programmes. All the women were examined every 3 mth and a blind assessment made of the menopausal index estimated according to Kupperman et al. The data revealed a highly significant reduction in climacteric symptoms in the hormone-treated women as compared with the placebo group (P less than 0.001), a highly significant dose relationship between climacteric symptoms and treatment with 4, 2 and 1 mg oestradiol, respectively (P less than 0.001), a highly significant and dose-dependent rebound phenomenon after withdrawal of hormone treatment (P less than 0.001)--which levelled off after 6 mth following withdrawal--and complete relief of hot flushes with the two highest doses of oestradiol (4 and 2 mg oestradiol). It is concluded that sex hormones have a beneficial effect in post-menopausal women with even mild symptoms.", "To determine the effect of continuous combined treatment with norethindrone acetate and ethinyl estradiol (E2) on vaginal bleeding, spotting, or bleeding and/or spotting in postmenopausal women.\n Two randomized clinical trials were conducted in which participants recorded information on the daily occurrence of vaginal bleeding or spotting. In study 1, 219 postmenopausal women reporting at least ten hot flushes per week were randomized to placebo or one of four treatment groups (0.2 mg norethindrone acetate/1 microg ethinyl E2, 0.5 mg norethindrone acetate/2.5 microg ethinyl E2, 1 mg norethindrone acetate/5 microg ethinyl E2, or 1 mg norethindrone acetate/10 microg ethinyl E2). In study 2, 266 postmenopausal women reporting at least 56 moderate to severe hot flushes were randomized to placebo or one of three treatment groups (0.5 mg norethindrone acetate/2.5 microg ethinyl E2, 1 mg norethindrone acetate/5 microg ethinyl E2, or 1 mg norethindrone acetate/10 microg ethinyl E2). The total duration of treatment was 16 weeks in study 1 and 12 weeks in study 2. In both studies, subjects reported in daily diaries whether they had either bleeding or spotting.\n In study 1, there was a significantly greater relative risk (RR) for bleeding in the group receiving 1 mg norethindrone acetate/10 microg ethinyl E2 at study weeks 4 and 8 (RR = 1.36 and 95% confidence interval [CI] 1.01, 1.83; RR = 1.37 and 95% CI 1.1, 1.72; respectively) compared with placebo, but not at study weeks 12 or 16. The group receiving 1 mg norethindrone acetate/5 microg ethinyl E2 also had a significantly greater risk at weeks 4 and 8 (RR = 1.5 and 95% CI 1.15, 1.96; RR = 1.33 and 95% CI 1.00, 1.77; respectively), whereas the other dose combinations did not differ from placebo. Results from study 2 were similar to those of study 1.\n Although there was a greater risk for bleeding and/or spotting at the higher doses of norethindrone acetate and ethinyl E2, this risk declined over time. If compliance with hormone replacement therapy regimens is influenced at least in part by vaginal bleeding, the combined norethindrone acetate/ethinyl E2 regimen investigated in these studies may provide a treatment option.", "To assess the effects of oral E2 replacement therapy combined with nomegestrol acetate, a 19-norprogesterone derivative, on cardiovascular risk factors.\n A double-blind randomized prospective study comparing the effect of a placebo and two oral E2-nomegestrol acetate combinations (1 mg-2.5 mg and 1.5 mg-3.75 mg) over a three-cycle trial.\n Department of Internal Medicine and Nutrition, Hotel-Dieu, Paris, France.\n Fifty-seven nonhysterectomized women with natural menopause.\n Blood pressure, renin substrate, glucose, total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, apoproteins A1 and B, lipoprotein(a), antithrombin III, fibrinogen, plasminogen, prothrombin fragment 1 + 2, protein C, and total and free protein S.\n Both treatments significantly reduced menopausal complaints, total cholesterol, low-density lipoprotein cholesterol and lipoprotein(a). Treatment with the 1.5 mg-3.75 mg combination resulted in a significant increase in apolipoprotein A1. No significant change were observed in other parameters.\n Sequentially combined with oral E2 in hormone replacement therapy, nomegestrol acetate had favorable effects on plasma lipids and lipoproteins. This nonandrogenic progestin decreased lipoprotein(a) levels as observed previously with medroxyprogesterone acetate combined with conjugated equine estrogens.", "A randomised, double-blind, cross-over study into the effect of graded sequential mestranol and norethisterone on climacteric symptoms was performed. The study group consisted of 23 post-menopausal women who had previously undergone hysterectomy. Active therapy resulted in a significant reduction in hot flushes and night sweats. There was a slight improvement in insomnia, lack of energy and confidence but the other symptoms were not significantly altered. A small placebo effect was noted but this was only significant 1 mth after active treatment had been discontinued in the group of women receiving placebo second. Active treatment also resulted in a significant reduction in serum sodium, calcium, albumin, alkaline phosphatase and cholesterol, and increase in serum triglycerides, but no alteration in the other biochemical parameters, weight or blood pressure.", "In a double-blind study on the value of equine (\"natural\") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months' hormone treatment followed by three months' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.", "With the aim of preventing postmenopausal bone loss, a placebo-controlled double-blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17 beta-oestradiol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D3); fluoride and D3; and 1 alpha (OH) vitamin D3 0.25 microgram/day (1 alpha D3). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%). The combined placebo groups showed a linear fall in BMC reaching 3.3% after 2 years (P < 0.001). Hormones and hormones and thiazide led to a 2.5% gain in BMC (P < 0.01). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1.5% (P < 0.05), less than that of the placebo group (P < 0.05). BMC declined by 3.6%, 4.5%, 3.7% and 3.7% during the respective use of fluoride, D3, fluoride and D3 and 1 alpha D3. Nevertheless, the urinary calcium excretion during 1 alpha D3 and D3 treatment was 1--1.5 mmol/day higher than in the placebo groups. Apparently, there is no real alternative to oestrogen/gestagen in the prevention of postmenopausal osteoporosis.", "OBJECTIVE -- The purpose of the study was to determine the efficacy of sequential 17 beta-estradiol and norethindrone acetate (Trisequens) in the relief of vasomotor symptoms by comparing the quality of life data from questionnaires, number and severity of symptoms, and the dropout rate versus placebo treatment. STUDY DESIGN -- Women 40 to 60 years old, who spontaneously complained of menopausal symptoms, were randomly allocated to four consecutive cycles with Trisequens (n = 40) or placebo (n = 42). Analysis of variance and two-tailed tests (P < .05) for all comparisons were used. RESULTS -- The mean number of pretreatment vasomotor symptoms per day was 7 (1.3 severe) for Trisequens and 6 (1.8 severe) for placebo, whereas posttreatment a reduction to 1.3 (0.1 severe) versus 4.2 (1.8 severe), respectively, was observed. Quality of life scores, utilizing the Kupperman Scale, 3-Factor Green Index, and Beck Depression Inventory all produced statistically significant differences (P = 0.0015, 0.0037, 0.0026, 0.0003, 0.0242, respectively). The dropout rate difference between groups was significant (P = 0.028): 12 from the Trisequens group and 23 from the placebo group. CONCLUSION -- Trisequens significantly improves vasomotor symptoms. Quality of life rating scales provide additional data to support the utility of sequential estrogen/progestin treatment for menopause therapy.", "Acute menopausal symptoms occur less frequently in Asian than in Caucasian women. Oestrogen replacement therapy has been shown to be effective in controlling acute symptoms in Caucasians, but the effect of oestrogens is not well documented in Asian women. A randomized, double-blind, placebo-controlled, crossover study of the effect of oral oestradiol on the incidence of acute menopausal symptoms was conducted in 83 Hong Kong Chinese women who had experienced a surgical menopause. Although there was a significant increase in the oestradiol concentration with treatment compared with placebo (P < 0.001), there were no significant differences in the reporting of symptoms between the treatment and placebo groups. There is no obvious explanation for this apparent lack of effect of oestrogen on acute menopausal symptoms in Chinese women. Whilst it may be related to the generally low incidence of symptoms or to a higher dietary intake of phytoestrogens in Chinese women, further studies are necessary to explain these findings.", "Continuous combined therapy (CCT) using estrogens and progestagens has appeared as an alternative to avoid vaginal bleeding, which is characteristic of sequential hormone therapy, and the main reason for the stopping treatment. Irregular vaginal bleeding can occur at the beginning of treatment, but it has been observed that after a few months patients are in amenorrhea. Fifty postmenopausal women were studied in order to evaluate the clinical outcome. Half of them were treated with a product containing 2 mg estradiol valerate and 2.5 mg medroxiprogesterone acetate, while the other half received a placebo. Menopause symptomatology was recorded as described by Blatt-Kupperman, depression was evaluated with the use of Hamilton's test, lipid profile by enzymatic methods and endometrial thickness by transvaginal ultrasonography. Patients were evaluated at the beginning, third and sixth month of the study, following a double blind methodology. Symptomatology diminished both in patients under CCT and using placebo, although improvement was significantly greater in patient under CCT. Thus in the hormone treated group the Blatt-Kupperman score fell from 12.1 to 6.4 and 3.2 in the third and sixth month respectively, while in the group receiving placebo the score fell from 11.5 to 6.3 in the third month and raised to 7.4 in the sixth month. Hamilton's test showed a significant improvement of depression only in patients under hormone therapy. Nineteen out of twenty five women using CCT had vaginal bleeding, showing no changes in the endometrial thickness during the study. Finally, HDL-cholesterol was raised in 14.5% while LDL-cholesterol was lowered in 18.7% (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)" ]