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[ "9751087", "10622295" ]

[ "Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.", "Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group." ]

[ "To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients.\n In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26.\n Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients.\n Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.", "Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate.\n In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks.\n At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group.\n During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate." ]

[ "17534702" ]

[ "Evaluation of a short-form functional capacity evaluation: less may be best." ]

[ "Functional Capacity Evaluation (FCE) contributes to clinical decisions regarding fitness-for-work and may improve return-to-work outcomes. However, FCE is a burdensome clinical tool in terms of time and cost. We evaluated the effectiveness of a short-form FCE protocol.\n A cluster randomized controlled trial was conducted. Data were collected on all claimants undergoing FCE at Alberta's workers' compensation rehabilitation facility. Twenty-three clinicians who were trained and experienced with FCE were randomized to either an intervention or control group. The intervention group was trained to conduct short-form FCE and used this protocol through the trial's duration, while the control group continued standard FCE procedures. Data on subject characteristics, administrative outcomes (days to suspension of time loss benefits, days to claim closure, and future recurrence) and claimant satisfaction were extracted from the WCB-Alberta computer databases. Clinicians logged time taken to complete assessments. Analysis included examining differences between groups using independent samples t tests, Cox and logistic regression.\n Subjects included 372 claimants of whom 173 were tested with short-form FCE. Subjects were predominantly employed (64%) males (69%) with chronic musculoskeletal conditions (median duration 252 days). Administrative recovery outcomes were similar between groups as were claimant satisfaction ratings. No statistically significant or clinically relevant differences were observed on these outcomes between groups. A 43% reduction in functional assessment time was seen.\n A short-form FCE appears to reduce time of assessment while not affecting recovery outcomes when compared to standard FCE administration. Such a protocol may be an efficient option for therapists performing fitness-for-work assessments." ]

[ "17485450" ]

[ "Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial." ]

[ "The purpose of this work was to compare the efficacy of propofol, a hypnotic agent, to the regimen of morphine, atropine, and suxamethonium as an induction agent for nonemergency neonatal endotracheal intubation. We hypothesized that propofol aids intubation by allowing the continuation of spontaneous breathing.\n We conducted a randomized, open-label, controlled trial of infants who required nonemergency endotracheal intubation. Primary outcome was successful intubation confirmed by chest auscultation and clinical examination of the infant.\n Infants randomly assigned to propofol (n = 33) and the morphine, atropine, and suxamethonium regimen (n = 30) were comparable in median gestational age (27 vs 28 weeks), birth weight (1020 vs 1095 g), weight at intubation (1068 vs 1275 g), and age at intubation (4 vs 3 days). Sleep or muscle relaxation were achieved within 60 seconds in both groups, but time to achieve successful intubation was more than twice as fast with propofol (120 vs 260 seconds). Blood pressure and heart rates were not different, but intraprocedural oxygen saturations were significantly lower in infants on the morphine, atropine, and suxamethonium regimen (trough arterial oxygen saturation: 60% vs 80%). Nasal/oral trauma was less common, and recovery time was shorter (780 vs 1425 seconds) in the propofol group. No significant adverse effects were seen in either group.\n Propofol is more effective than the morphine, atropine, and suxamethonium regimen as an induction agent to facilitate neonatal nasal endotracheal intubation. Importantly, hypoxemia was less severe, probably because of the maintenance of spontaneous breathing. A controlled environment may have promoted the ease of intubation, resulting in less trauma. The shorter duration of action would be advantageous in a compromised infant." ]

[ "10851374", "11502921", "12743240", "11160953", "17335465", "9415509", "17662571", "17161535", "18428211", "11973012", "10506679" ]

[ "A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy.", "Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study.", "Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial.", "Lamotrigine for central poststroke pain: a randomized controlled trial.", "Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy.", "Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial.", "Double-blind, placebo-controlled trial of lamotrigine in combination with other medications for neuropathic pain.", "Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies.", "Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3.", "Lamotrigine in spinal cord injury pain: a randomized controlled trial.", "200 mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind, placebo controlled trial." ]

[ "To investigate the analgesic efficacy of lamotrigine in the treatment of painful HIV-associated distal sensory polyneuropathy (DSP).\n The pathogenesis of HIV-associated DSP is unknown and there is no effective treatment. A novel anticonvulsant, lamotrigine, blocks voltage-sensitive sodium channels and inhibits the release of glutamate and aspartate. There have been anecdotal reports of efficacy of lamotrigine in the treatment of painful neuropathy and trigeminal neuralgia.\n In a multicenter, randomized, double-blind, placebo-controlled study, lamotrigine was initiated at 25 mg per day and slowly titrated over 7 weeks to 300 mg per day. Study duration was 14 weeks. The primary outcome measure was change in pain on the modified Gracely scale with secondary outcome measures including change in neurologic examination, use of concomitant analgesic medications, and global pain relief.\n Of 42 enrolled subjects, 13 did not complete the 14-week study endpoint. In five of these, rash was the cause for dropout. In the remaining 29 evaluable subjects, 20 patients received placebo and 9 received lamotrigine. The pain scores at baseline were not significantly different. The reduction in average pain from baseline to week 14 was greater (p = 0.03) in the lamotrigine group (-0.55) than in the placebo group (-0.18), adjusting for baseline levels of pain. There was no difference between the groups on the change in peak worst pain.\n In this small trial, lamotrigine showed promise in the treatment of pain associated with HIV-related DSP. The frequency of rash was greater than in lamotrigine studies in epilepsy. A larger controlled study of lamotrigine is warranted.", "To study the efficacy of lamotrigine in relieving the pain associated with diabetic neuropathy.\n The authors randomly assigned 59 patients to receive either lamotrigine (titrated from 25 to 400 mg/day) or placebo over a 6-week period. Primary outcome measure was self-recording of pain intensity twice daily with a 0 to 10 numerical pain scale (NPS). Secondary efficacy measures included daily consumption of rescue analgesics, the McGill Pain Questionnaire (MPQ), the Beck Depression Inventory (BDI), the Pain Disability Index (PDI), and global assessment of efficacy and tolerability.\n Twenty-four of 29 patients (83%) receiving lamotrigine and 22 of 30 (73%) patients receiving placebo completed the study. Daily NPS in the lamotrigine-treated group was reduced from 6.4 +/- 0.1 to 4.2 +/- 0.1 and in the control group from 6.5 +/- 0.1 to 5.3 +/- 0.1 (p < 0.001 for lamotrigine doses of 200, 300, and 400 mg). The results of the MPQ, PDI, and BDI remained unchanged in both groups. The global assessment of efficacy favored lamotrigine treatment over placebo, and the adverse events profile was similar in both groups.\n Lamotrigine is effective and safe in relieving the pain associated with diabetic neuropathy.", "To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies.\n In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART).\n The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p </= 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo.\n Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.", "Central poststroke pain (CPSP) is usually difficult to treat. Amitriptyline, the only oral preparation shown to be effective in a randomized controlled trial, is often associated with a range of side effects related to the many mechanisms of actions of tricyclic antidepressants. We investigated the effect of lamotrigine, a drug that reduces neuronal hyperexcitability, on poststroke pain.\n Thirty consecutive patients with CPSP (median age 59 years, range 37 to 77; median pain duration 2.0 years, range 0.3 to 12) from two centers participated in a randomized, double-blind, placebo-controlled cross-over study. The study consisted of two 8-week treatment periods separated by 2 weeks of wash-out. The primary endpoint was the median value of the mean daily pain score during the last week of treatment while treated with 200 mg/d lamotrigine. Secondary endpoints were median pain scores while on lamotrigine 25 mg/d, 50 mg/d, and 100 mg/d; a global pain score; assessment of evoked pain; areas of spontaneous pain; and allodynia/dysesthesia.\n Lamotrigine 200 mg/d reduced the median pain score to 5, compared to 7 during placebo (p = 0.01) in the intent-to-treat population of 27 patients. No significant effect was obtained at lower doses. Twelve patients (44%) responded to the treatment. There was a uniform tendency to reduction of all secondary outcome measures, but lamotrigine only had significant effects on some of the secondary outcome measures. Lamotrigine was well tolerated with few and transient side effects. Two mild rashes occurred during lamotrigine treatment, one causing withdrawal from study.\n Oral lamotrigine 200 mg daily is a well tolerated and moderately effective treatment for central poststroke pain. Lamotrigine may be an alternative to tricyclic antidepressants in the treatment of CPSP.", "To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients.\n A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 53). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time, each dose for 2 weeks, and lamotrigine orally, at doses of 25, 50 and 100 mg twice daily, each dose for 2 weeks, by optional titration were used. There was a placebo washout period for 2 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out.\n Good, moderate and mild pain relief were noted in 19 (41%), six (13%) and seven (15%) patients on lamotrigine and 13 (28%), five (11%) and 15 (33%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physicians global assessment, McGill pain questionnaire and Likert pain scale showed no significant difference between the treatments, although improvement with both treatments was seen from 2 weeks. Of the 44 adverse events reported, 33 (75%) were with amitriptyline, sedation being the commonest [in 19 (43%) patients]. Lamotrigine caused adverse events in 11 (25%), of which rash in three (7%) and elevations of creatinine in four (9%) were the most common. The preferred lamotrigine dose was 25 mg twice daily.\n As there are few differences between the two treatments in efficacy, lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population.", "Lamotrigine is a chemically novel antiepileptic drug which has not been adequately assessed for its antineuralgic properties. It was used in a double-blind placebo controlled crossover trial in 14 patients with refractory trigeminal neuralgia. Patients continued to take a steady dose of carbamazepine or phenytoin throughout the trial over a 31-day period. Each arm of the trial lasted 2 weeks with an intervening 3-day washout period. The maintenance dose of lamotrigine was 400 mg. Lamotrigine was superior to placebo (P = 0.011) based on analysis of a composite efficacy index which compared the numbers of patients assigned greater efficacy on lamotrigine with those assigned greater efficacy on placebo. Efficacy for one treatment over another was determined according to a hierarchy of: (i) use of escape medication; (ii) total pain scores; or (iii) global evaluations. Eleven of the 13 patients eligible for inclusion in the composite efficacy index showed better efficacy on lamotrigine compared with placebo. Global evaluations further suggested that patients did better on lamotrigine than placebo (P = 0.025). The adverse reactions with both lamotrigine and placebo were predominantly dose-dependent effects on the central nervous system. A 14th patient withdrew from the study due to severe pain during the placebo arm of the trial. It would appear that lamotrigine has antineuralgic properties.", "This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and tolerability of lamotrigine added to gabapentin, a tricyclic antidepressant, or a nonopioid analgesic in patients whose neuropathic pain was inadequately controlled with these medications. Patients with neuropathic pain from diabetic peripheral neuropathy, postherpetic neuralgia, traumatic/surgical nerve injury, incomplete spinal cord injury, trigeminal neuralgia, multiple sclerosis, or HIV-associated peripheral neuropathy, who had a mean weekly pain score > or =4 on an 11-point numerical rating scale, were randomized to receive a flexible dose of lamotrigine 200, 300, or 400mg daily (n=111) or placebo (n=109) for up to 14 weeks (including eight weeks of dose escalation) in addition to their prestudy regimen of gabapentin, a tricyclic antidepressant, or a nonopioid analgesic. No statistically significant difference in the mean change in pain-intensity score from baseline to Week 14 (primary endpoint) was detected between lamotrigine and placebo (P=0.67). Differences between lamotrigine and placebo were not statistically significant for secondary efficacy assessments, including mean changes from baseline in the Short-Form McGill Pain Questionnaire, the Neuropathic Pain Scale, rescue medication use, and the percentages of patients rated as much improved or very much improved at the end of treatment on the Clinician Global Impression of Change scale and the Patient Global Impression of Change scale. Lamotrigine was generally well tolerated. Lamotrigine (up to 400 mg/day) added to gabapentin, a tricyclic antidepressant, or a nonopioid analgesic did not demonstrate efficacy as an adjunctive treatment of neuropathic pain but was generally safe and well tolerated.", "To assess the efficacy and tolerability of lamotrigine in pain associated with diabetic neuropathy, two replicate randomized, double-blind, placebo-controlled studies were conducted. Patients (n=360 per study) with painful diabetic neuropathy were randomized to receive lamotrigine 200, 300, or 400 mg daily or placebo during the 19-week treatment phase, including a 7-week dose-escalation phase and a 12-week, fixed-dose maintenance phase. The mean reduction in pain-intensity score from baseline to week 19 (primary endpoint) was greater (p < or = 0.05) in patients receiving lamotrigine 400 mg than placebo in Study 2 (observed scores, -2.7 versus -1.6 on a 0- to 10-point scale). This finding was not replicated in Study 1. Lamotrigine 200 and 300 mg did not significantly differ from placebo at week 19 in either study. Lamotrigine 300 and 400 mg were only occasionally more effective than placebo for secondary efficacy endpoints. The 200-mg dose did not separate from placebo. In a post hoc analysis of pooled data including only patients who reached their target dose, lamotrigine 400 mg conferred greater (p0.05) mean reduction in pain-intensity score from baseline to week 19 than placebo (-2.5 for 300 mg and -2.7 for 400mg versus -2.0 for placebo). Adverse events were reported in 71-82% of lamotrigine-treated patients compared with 63-70% of placebo-treated patients. The most common adverse events with lamotrigine were headache and rash. Compared with placebo, lamotrigine (300 and 400 mg daily) was inconsistently effective for pain associated with diabetic neuropathy but was generally safe and well tolerated.", "Lamotrigine, an antiepileptic agent, has been reported as being effective in reducing symptoms of neuropathy associated with various etiologies. Based on such data, a multicenter double-blind, placebo-controlled, randomized trial was conducted to evaluate the effect of lamotrigine on pain and other neuropathic symptoms due to chemotherapy-induced peripheral neuropathy (CIPN).\n Patients with symptomatic CIPN with symptom scores of either 1) >3 on a 0-10 Numerical Rating Scale (NRS) or 2) >1 on the 0-3 the Eastern Cooperative Oncology Group (ECOG) neuropathy scale (ENS) were eligible (higher numbers corresponding to greater severity of symptoms in both scales). Patients were randomly assigned to receive lamotrigine (target dose of 300 mg/day) or placebo for 10 weeks. Endpoints were measured biweekly.\n In all, 131 patients were enrolled. Both groups were well matched at baseline. Over the 10-week period of the trial, the average pain scores (NRS) for the lamotrigine and placebo arms declined in both arms, with no statistically significant difference noted between the changes in the 2 groups (0.3 and 0.5 unit reduction from baseline, respectively; P=.56). Similarly, decreases in the ENS with therapy were not statistically different (0.4 and 0.3, respectively; P=.3). Changes in other subjective symptom scales were also not found to be statistically different between the 2 groups. Toxicities were mild and similar in each group.\n The results suggest that lamotrigine is not effective for relieving neuropathic symptoms in patients because of CIPN.\n Copyright (c) 2008 American Cancer Society.", "The objective was to investigate the effectiveness of lamotrigine for the treatment of spinal cord injury pain and clinical signs of neuronal hyperexcitability. Thirty patients with spinal cord injury (SCI) and at or below level neuropathic pain participated in a randomized double blind, placebo-controlled, crossover trial. A 1-week baseline period was followed by two treatment periods of 9 weeks duration with lamotrigine slowly increased to a maximum of 400 mg or placebo separated by a 2-week washout period. The primary outcome measure was the change in median pain score from baseline week to the last week of treatment. Secondary outcome measures included thresholds to standardized sensory stimuli using quantitative sensory testing. Twenty-two patients completed the trial. We found no statistically significant effect of lamotrigine as evaluated in the total sample. However, in patients with incomplete SCI, lamotrigine significantly reduced pain at or below SCI level. Patients with brush evoked allodynia and wind-up-like pain in the area of maximal pain were more likely to have a positive effect to lamotrigine than patients without these evoked pains (7 of 7 vs. 1 of 14). Lamotrigine was generally well tolerated. While this trial showed no significant effect on spontaneous and evoked pain in complete and incomplete spinal cord injury, lamotrigine reduced spontaneous pain in patients with incomplete spinal cord injury and evoked pain in the area of spontaneous pain.", "Anticonvulsant drugs are commonly used in neuropathic pain. There is anecdotal evidence of an analgesic effect of the anticonvulsant lamotrigine in neuropathic pain, but this is verified by few randomised controlled trials. This randomised, double-blind, placebo controlled trial of examined the effect of lamotrigine in a dose increasing to 200 mg in 100 patients with neuropathic pain. Eight patients failed to attend for review, 18 withdrew early and 74 provided results. There was no statistical difference in age, sex or duration pre-treatment pain in the two groups. Total pain, the character of the pain, sensitivity, numbness, paraesthesia, sleep, mobility, mood, quality of life and analgesic consumption were measured. There was a correlation between burning and numbness (P<0. 01), shooting pain and total pain (P<0.01) and between analgesic consumption and mobility (P<0.05) throughout the study period. There were no correlation between any other measured variable. There was no significant change in any variable measured over the eight week period when lamotrigine was used. It is concluded that at the dose used and using the dose escalation regime described, lamotrigine had no effect on either pain, component pain symptoms or quality of life variables." ]

[ "17214404", "16323382", "19199362", "19561035", "20878048", "16720935", "21425338", "18295614", "16392539", "19265758" ]

[ "Proprioceptive and sensorimotor performance in Parkinson's disease.", "Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.", "Effect of whole body vibration in Parkinson's disease: a controlled study.", "Vibration therapy in multiple sclerosis: a pilot study exploring its effects on tone, muscle force, sensation and functional performance.", "Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.", "The effects of random whole-body-vibration on motor symptoms in Parkinson's disease.", "Acute effects of whole-body vibration at 3, 6, and 9 hz on balance and gait in patients with Parkinson's disease.", "Whole body vibration versus conventional physiotherapy to improve balance and gait in Parkinson's disease.", "Effects of random whole-body vibration on postural control in Parkinson's disease.", "Acute effects of whole-body vibration on lower extremity muscle performance in persons with multiple sclerosis." ]

[ "We explored the effects of random whole-body vibration on leg proprioception in Parkinson's disease (PD). In earlier studies it was found that this treatment leads to improved postural control in these patients. Thus, one could speculate that these effects result from modified proprioceptive capabilities. Twenty-eight PD patients were subdivided in one experimental and one control group. Proprioceptive performance was analyzed using a tracking task basing on knee extension and flexion movements. Treatment consisted of 5 series of random whole-body vibration taking 60 seconds each. Control subjects had a rest period instead. Prominent over- and undershooting errors were found in both groups representing proprioceptive impairments. No significant differences became evident, however, either between pre- and post-tests or between experimental and control group. One might therefore conclude that spontaneous improvements in postural control are not directly connected with proprioceptive changes. Nevertheless, one also should keep in mind the general aspects and difficulties of analyzing proprioception.", "To examine whether a whole-body vibration (mechanical oscillations) in comparison to a placebo administration leads to better postural control, mobility and balance in patients with multiple sclerosis.\n Double-blind, randomized controlled trial.\n Outpatient clinic of a university department of physical medicine and rehabilitation.\n Twelve multiple sclerosis patients with moderate disability (Kurtzke's Expanded Disability Status Scale 2.5-5) were allocated either to the intervention group or to the placebo group.\n In the intervention group a whole-body vibration at low frequency (2.0-4.4 Hz oscillations at 3-mm amplitude) in five series of 1 min each with a 1-min break between the series was applied. In the placebo group a Burst-transcutaneous electrical nerve stimulation (TENS) application on the nondominant forearm in five series of 1 min each with a 1-min break between the series was applied as well.\n Posturographic assessment using the Sensory Organization Test, the Timed Get Up and Go Test and the Functional Reach Test immediately preceding the application, 15 min, one week and two weeks after the application. The statistical analysis was applied to the change score from preapplication values to values 15 min, one week and two weeks post intervention.\n Compared with the placebo group the intervention group showed advantages in terms of the Sensory Organization Test and the Timed Get Up and Go Test at each time point of measurement after the application. The effects were strongest one week after the intervention, where significant differences for the change score (p = 0.041) were found for the Timed Get Up and Go Test with the mean score reducing from 9.2 s (preapplication) to 8.2 s one week after whole-body vibration and increasing from 9.5 s (preapplication) to 10.2 s one week after placebo application. The mean values of the posturographic assessment increased from 70.5 points (preapplication) to 77.5 points one week after whole body vibration and increased only from 67.2 points (preapplication) to 67.5 points one week after the placebo application. No differences were found for the Functional Reach Test.\n The results of this pilot study indicated that whole-body vibration may positively influence the postural control and mobility in multiple sclerosis patients.", "In the search of new strategies to improve the quality of life of Parkinson's disease patients, recent work has reported an amelioration of Parkinsonian symptoms using Whole Body Vibration (WBV). A double-blinded, placebo controlled design was used to evaluate the effect of a 12 WBV sessions-programme on a number of motor and clinical tests in 23 Parkinson's disease patients. Patients were assigned to one of two groups, one receiving WBV and the other a placebo group. At the end of the programme as well as during intra-session evaluation, there was no difference between the experimental (vibration) and placebo groups in any outcomes. These results suggest that reported benefits of vibration are due to a placebo response.\n (c) 2009 Movement Disorder Society.", "To examine the effectiveness of whole body vibration (WBV) on tone, muscle force, sensation and functional performance in people with multiple sclerosis.\n A randomized cross-over pilot study.\n Revive MS Support Therapy Centre. Glasgow, UK.\n Sixteen people with multiple sclerosis were randomly allocated to one of two groups.\n Group 1 received four weeks of whole body vibration plus exercise three times per week, two weeks of no intervention and then four weeks of exercise alone three times per week. Group 2 were given the two treatment interventions in the reverse order to group 1.\n Ten-metre walk, Timed Up and Go Test, Modified Ashworth Scale, Multiple Sclerosis Spasticity Scale (MSSS-88), lower limb muscle force, Nottingham Sensory Assessment and Multiple Sclerosis Impact Scale (MSIS-29) were used before and after intervention.\n The exercise programme had positive effects on muscle force and well-being, but there was insufficient evidence that the addition of whole body vibration provided any further benefit. The Modified Ashworth Scale was generally unaffected by either intervention, although, for each group, results from the MSSS-88 showed whole body vibration and exercises reduced muscle spasms (P = 0.02). Although results for the 10-m walk and Timed Up and Go Test improved, this did not reach statistical significance (P = 0.56; P = 0.70, respectively). For most subjects sensation was unaffected by whole body vibration.\n Exercise may be beneficial to those with multiple sclerosis, but there is limited evidence that the addition of whole body vibration provides any additional improvements. Further larger scale studies into the effects of whole body vibration in people with multiple sclerosis are essential.", "To investigate the acute effects of long-term whole-body vibration on leg muscle performance and functional capacity in persons with multiple sclerosis.\n A randomized controlled trial.\n Twenty-five patients with multiple sclerosis (mean age 47.9 ± 1.9 years; Expanded Disability Status Scale 4.3 ± 0.2) were assigned randomly to whole-body vibration training (n = 11) or to a control group (n = 14).\n The whole-body vibration group performed static and dynamic leg squats and lunges on a vibration platform (25-45 Hz, 2.5 mm amplitude) during a 20-week training period (5 training sessions per 2-week cycle), and the control group maintained their usual lifestyle. PRE-, MID- (10 weeks) and POST- (20 weeks) knee-muscle maximal isometric and dynamic strength, strength endurance and speed of movement were measured using isokinetic dynamometry. Function was determined through the Berg Balance Scale, Timed Up and Go, Two-minute Walk Test and the Timed 25-Foot Walk Test.\n Leg muscle performance and functional capacity were not altered following 10 or 20 weeks of whole-body vibration.\n Under the conditions of the present study, the applied 20-week whole-body vibration exercise protocol did not improve leg muscle performance or functional capacity in mild- to moderately impaired persons with multiple sclerosis during and immediately after the training programme.", "It is well known that applying vibrations to men influences multiple physiological functions. The authors analysed post effects of whole-body-vibration (WBV) on motor symptoms in Parkinson's disease (PD). Sixty-eight persons with PD were randomly subdivided into one experimental and one control group. Motor symptoms were assessed by the UPDRS (Unified Parkinson's Disease Rating Scale) motor score. A cross-over design was used to control treatment effects. The treatment consisted of 5 series of whole-body-vibration taking 60 seconds each. On average a highly significant (p<0.01) improvement of 16.8% in the UPDRS motor score was found in the treatment group. Only marginal changes (p>0.05) were found in the control group. The cross-over procedure showed comparable treatment effects (14.7% improvement after treatment). With respect to different symptom clusters only small changes were found in limb akinesia and cranial symptoms. By contrast, tremor and rigidity scores were improved by 25% and 24%, respectively. According to the structure of symptom changes it is unlikely that these effects are explainable on peripheral sensory level, exclusively. With respect to the findings of other studies one can speculate about changes in activation of the supplementary motor area and in neurotransmitter functions.", "nan", "To compare the effects of whole body vibration (WBV) and conventional physiotherapy (PT) on levodopa-resistant disturbances of balance and gait in idiopathic Parkinson's disease (PD).\n Randomized controlled rater-blinded trial comparing 2 active interventions, final follow-up assessment 4 weeks after termination of active intervention.\n Specialized referral center, hospitalized care.\n Patients with PD and dopa-resistant imbalance on stable dopamine replacement medication (N=27) were randomized (intent-to-treat population) to receive WBV (n=13) or conventional PT (controls, n=14). Twenty-one patients (per protocol population) completed follow-up (14 men, 7 women; mean age, 73.8 y; age range, 62-84 y; mean disease duration, 7.2 y; mean dopa-equivalent dose, 768 mg/d).\n Subjects were randomized to receive 30 sessions (two 15-min sessions a day, 5 days a week) of either WBV on an oscillating platform or conventional balance training including exercises on a tilt board. Twenty-one subjects (10 with WBV, 11 controls) were available for follow-up 4 weeks after treatment termination.\n The primary measure was Tinetti Balance Scale score. Secondary clinical ratings included stand-walk-sit test, walking velocity, Unified Parkinson's Disease Rating Scale (section III motor examination) score, performance in the pull test, and dynamic posturography.\n The Tinetti score improved from 9.3 to 12.8 points in the WBV group and from 8.3 to 11.7 in the controls. All secondary measures, except posturography, likewise improved at follow-up compared with baseline in both groups. Quantitative dynamic posturography only improved in patients with WBV (1937-1467 mm) whereas there was no significant change in controls (1832-2030 mm).\n Equilibrium and gait improved in patients with PD receiving conventional WBV or conventional PT in the setting of a comprehensive rehabilitation program. There was no conclusive evidence for superior efficacy of WBV compared with conventional balance training.", "We investigated spontaneous effects of random whole-body vibration (rWBV) on postural control in Parkinsonian subjects. Effects were examined in biomechanical tests from a total of 52 patients divided equally into one experimental and one control group. Postural control was tested pre- and post-treatment in two standardized conditions (narrow standing and tandem standing). The intervention was based on rWBV (ŷ: 3 mm, f: 6 Hz 1 Hz/sec) consisting of 5 series lasting 60 seconds each. The main findings from this study were that (1) rWBV can improve postural stability in Parkinson's disease (PD) spontaneously (2) these effects depend on the test condition. Based on the results of this study, rWBV can be regarded as an additional device in physical therapy in PD.", "Whole-body vibration (WBV) is a relatively new form of exercise training that may influence muscle performance. This study investigated the acute effects of high- (26 Hz) and low- (2 Hz) frequency WBV on isometric muscle torque of the quadriceps and hamstrings in persons with multiple sclerosis.\n Fifteen individuals (mean age = 54.6 years, SD = 9.6) with multiple sclerosis and Expanded Disability Status Scale scores ranging from 0 to 6.5 (mean = 4.2, SD = 2.3) participated in this randomized, crossover study. After baseline measures of isometric quadriceps and hamstring muscle torque, subjects were exposed to 30 seconds of WBV at either 2 or 26 Hz. Torque values were measured again at one, 10, and 20 minutes after vibration. Subjects returned one week later to repeat the same protocol at the alternate vibration frequency.\n There were no significant differences in isometric torque production between the 2- and 26-Hz WBV conditions. There was also no significant difference between baseline torque values and those measured at one, 10, and 20 minutes after either vibration exposure. However, there was a consistent trend of higher torque values after the 26-Hz WBV when compared with the 2-Hz condition for both quadriceps and hamstring muscles.\n Although not statistically significant, peak torque values for both quadriceps and hamstring muscles were consistently higher after 30 seconds of WBV at 26 vs 2 Hz. Whether WBV presents a viable treatment option as either a warm-up activity or a long-term exercise intervention is yet to be determined. Future studies should include a wider variety of WBV parameters and the use of functional outcome measures." ]

[ "3365008", "573185" ]

[ "Infant feeding and allergy.", "Soy versus cow's milk in infants with a biparental history of atopic disease: development of atopic disease and immunoglobulins from birth to 4 years of age." ]

[ "The effect of withholding cows' milk was examined in 487 infants at high risk of allergic disease. Before birth they were randomly allocated either to a control group, most of whom received cows' milk preparations, or to an intervention group, who were offered a soya based substitute. Eczema and wheezing occurred to a similar extent in the two groups during the first year of life, although napkin rash, diarrhoea, and oral thrush were commoner in the intervention group, especially during the first three months. Breast feeding for any length of time was associated with a reduced incidence of wheezing and diarrhoea.", "Forty-eight children with a biparental history of atopic disease were followed from birth to 4 years of age. One group was fed soy and the other cow's milk from weaning to 9 months of age. Two-thirds of the children developed symptoms of atopic disease with no significant difference between the groups. No difference was found in the serum immunoglobulins (IgE antibodies, IgA, IgG and IgM) during the observation period. The soy fed children showed transiently lower levels of IgG antibodies to cow's milk but higher levels of IgG antibodies to soy protein. Six children showed cow's milk intolerance and a further five had symptoms possibly related to the use of cow's milk. Withholding cow's milk during the first 9 months did not reduce the incidence of symptoms of cow's milk intolerance from birth to 4 years of age. Thus, no benefit was found from replacing cows' milk with soy. A prolonged breast feeding seems most rational for infants at risk of developing atopic disease, even if the present study did not show evidence of a prophylactic effect of breast milk against the development of atopic disease." ]

[ "9316673", "4136980" ]

[ "Postural tremor of Parkinson's disease.", "Letter: Propranolol in Parkinson's disease." ]

[ "Previous studies have reported the resting tremor (RT) of Parkinson's disease to occur at frequencies between 3-7 Hz and to be characterised by an alternating pattern of electromyographic (EMG) bursting activity between opposing muscles. A postural tremor (PT), of higher frequency (> 6 Hz) and with a synchronous pattern of EMG activity, has also been previously described in Parkinson's disease. We investigated the electrophysiological and pharmacological properties of both the RT and PT of 11 patients with Parkinson's disease and 10 patients with essential tremor in a double-blind, placebo-controlled study of L-Dopa/benserazide and propranolol. Tremor amplitude and frequency were assessed via bidirectional accelerometry, and the pattern of activation of the antagonist muscles of the forearm was determined with use of surface EMG. In the Parkinson's disease group studied, the frequency, EMG pattern of bursts, and response to L-Dopa were similar for the two tremors (median improvement of RT by 70% and PT by 61%). Despite some overlap between the Parkinson's disease and essential tremor groups in the electrophysiology of the tremor, there was no such dramatic pharmacological response in the latter group. These results suggest that the RT and PT of Parkinson's disease share a common pathophysiology and are distinct from essential tremor.", "nan" ]

[ "9111400", "3885685", "10884075", "15010154", "3673682", "3276422", "12931807", "16782569", "1430964", "9273452", "7995109", "15925158", "8732400", "12954254", "15142699", "11828556", "8408148", "12107308", "11861728", "16777857", "9330145", "7553006", "12002496", "9222908", "8543875", "2022828", "12809659" ]

[ "The role of epineurotomy in the operative treatment of carpal tunnel syndrome.", "Internal neurolysis or ligament division only in carpal tunnel syndrome--results of a randomized study.", "Early recovery after endoscopic vs. short-incision open carpal tunnel release.", "A randomized controlled trial of knifelight and open carpal tunnel release.", "Internal neurolysis or ligament division only in carpal tunnel syndrome. II. A 3 year follow-up with an evaluation of various neurophysiological parameters for diagnosis.", "Interfascicular neurolysis in the severe carpal tunnel syndrome. A prospective, randomized, double-blind, controlled study.", "Carpal tunnel release. A prospective, randomised study of endoscopic versus limited-open methods.", "Intra-individual comparison between open and 2-portal endoscopic release in clinically matched bilateral carpal syndrome.", "Endoscopic release of the carpal tunnel: a randomized prospective multicenter study.", "[Surgical treatment of carpal tunnel syndrome: endoscopic or classical (open)? A prospective randomized trial].", "[Carpal tunnel syndrome. Can it still be a controversial topic?].", "Mini-open blind procedure versus limited open technique for carpal tunnel release: a 30-month follow-up study.", "A prospective, randomized study with an independent observer comparing open carpal tunnel release with endoscopic carpal tunnel release.", "Early outcome and cost-effectiveness of endoscopic versus open carpal tunnel release: a randomized prospective trial.", "Carpal tunnel decompression. Is lengthening of the flexor retinaculum better than simple division?", "Carpal tunnel release by limited palmar incision vs traditional open technique: randomized controlled trial.", "Carpal tunnel release. A prospective, randomized assessment of open and endoscopic methods.", "Single-portal endoscopic carpal tunnel release compared with open release : a prospective, randomized trial.", "The role of flexor tenosynovectomy in the operative treatment of carpal tunnel syndrome.", "Outcomes of endoscopic surgery compared with open surgery for carpal tunnel syndrome among employed patients: randomised controlled trial.", "Ultrasonographically assisted carpal tunnel release.", "The value of one-portal endoscopic carpal tunnel release: a prospective randomized study.", "Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome. A prospective, randomised, blinded assessment.", "Local symptoms after open carpal tunnel release. A randomized prospective trial of two incisions.", "Early results of conventional versus two-portal endoscopic carpal tunnel release. A prospective study.", "Internal neurolysis fails to improve the results of primary carpal tunnel decompression.", "Evaluation of carpal tunnel release using the Knifelight instrument." ]

[ "We conducted a prospective, randomized study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal. Fifty hands (forty-four patients) were randomized into two groups: one group had a release of the transverse carpal ligament alone, and the other had a release and adjuvant epineurotomy of the median nerve. The groups were similar with regard to age, gender, duration of symptoms, and preoperative physical findings. All patients had electrophysiological evidence of sensory delays and fibrillations on preoperative testing. All of the operative procedures were performed by the same surgeon. The patients were evaluated preoperatively and at one year postoperatively. The follow-up examination revealed no detectable differences between the two groups with regard to symptoms, objective findings, or electrophysiological findings. This suggests that epineurotomy of the median nerve offers no benefit compared with sectioning of the transverse carpal ligament alone.", "In a series of patients with clinically and neurophysiologically well defined carpal tunnel syndrome a randomization has been made into two groups, one for operation with internal neurolysis and a microscopical technique, and the other group for cutting of the carpal ligament (flexor retinaculum) alone. The two groups have been compared postoperatively regarding clinical and neurophysiological parameters. All patients improved, 89% in both groups considered themselves totally free of symptoms at follow-up examinations but there was no significant difference in any parameter between the two groups. As a conclusion the use of internal neurolysis cannot be recommended as a routine procedure in carpal tunnel syndrome.", "Endoscopic carpal tunnel release has been claimed to offer improvement in recovery time and postoperative discomfort over open carpal tunnel release. Short-incision open carpal tunnel release has been claimed to offer recoveries comparable with endoscopic techniques. Patients receiving carpal tunnel surgery were randomized to short-incision open release or single-portal endoscopic release. Preoperative and postoperative evaluation included grip and pinch strength measurements and patient completion of a questionnaire regarding symptoms and function. Thirty-six operated hands completed evaluation, including 22 endoscopic and 14 open releases. Early grip and pinch strength after endoscopic carpal tunnel release were improved significantly over short-incision open release (p < 0.05). Subjective evaluation indicated a trend toward improved symptoms and function with endoscopic over short-incision open carpal tunnel release. Endoscopic carpal tunnel release provides faster recovery of strength than short-incision open carpal tunnel release and improves early postoperative comfort and function to a small degree.", "A randomized controlled trial was done to compare the results of carpal tunnel decompression using the standard open approach and the Knifelight technique. Twenty-six patients with bilateral carpal tunnel syndrome requiring operation were selected for the study and the operative technique was randomized for the first hand. Six weeks later, the second hand was operated upon using the alternate technique. There was little difference between the two techniques with regard to time taken to return to work, return of grip strength, symptom relief, complications, incidence of pillar pain and patient preference. However, the incidence of scar tenderness was significantly lower with the Knifelight technique.", "48 patients with clinical and neurophysiological signs of carpal tunnel syndrome were randomized to any of two operative methods: Internal neurolysis of the median nerve with a microsurgical technique, or simple division of the carpal ligament (flexor retinaculum). After a minimum follow-up period of 3 years 81% of the patients did not report any complaints at all, and all patients considered themselves improved after operation. There was no difference between the operation groups. Therefore there seems to be no justification to perform the more difficult procedure of internal microsurgical neurolysis for treatment of the carpal tunnel syndrome. A study of the neurophysiological parameters before and after restitution showed the highest sensitivity (91%) for the sensory conduction velocity, and the highest specificity for motor distal latency and sensory distal latency (83 and 75% resp.).", "There is significant difference of opinion whether an adjunctive interfascicular neurolysis will improve the results of lysis of the transverse carpal ligament in patients with severe carpal tunnel syndrome (thenar atrophy and/or fixed sensory deficit). Fifty such cases were prospectively and consecutively selected and then randomized into two groups prior to surgery. Half were treated by standard ligament release alone; the other half also had adjunctive interfascicular neurolysis. All patients had neurologic examination and nerve conduction studies performed by a \"blind\" examiner at one and three months postoperatively with comparison of these findings with preoperative data. Analysis of the data revealed no significant difference between the two groups and, therefore, demonstrated no benefit from adjunctive interfascicular neurolysis. Additionally, as the majority of patients in both groups improved significantly, the study demonstrated frequent benefit from transverse carpal ligament release even in the presence of fixed neurologic deficit in severe carpal tunnel syndrome.", "Endoscopic carpal tunnel release has the advantage over open release of reduced tissue trauma and postoperative morbidity. Limited open carpal tunnel release has also been shown to have comparable results, but is easier to perform and is safer. We have compared the results of both techniques in a prospective, randomised trial. Thirty patients with bilateral carpal tunnel syndrome had simultaneous bilateral release. The technique of release was randomly allocated to either two-portal endoscopic release (ECTR) or limited open release using the Strickland instrumentation (LOCTR). The results showed that the outcome was similar at follow-up of one year using both techniques. However, the LOCTR group had significantly less tenderness of the scar at the second and fourth postoperative week (p < 0.01). There was also less thenar and hypothenar (pillar) pain after LOCTR. Subjective evaluation showed a preference for LOCTR.", "Based upon bilateral carpal tunnel syndrome (CTS) we undertook a prospective randomised intra-individual comparison between open (OR) and 2-portal endoscopic release (2-PER) to establish if there is any demonstrable advantage in undertaking either technique in a 1 year follow-up. Ten patients with bilateral CTS were enrolled in this study and underwent a 2-PER on the one and an OR with two minimised incisions on the contralateral hand. Both hands were examined pre- and postoperatively after 2, 4, 6 and 12 weeks and after 6 and 12 months, respectively. Preoperatively both hands revealed statistically no significant differences in all the parameters recorded. Comparing both techniques no significant differences could be detected in the follow-up period. Nevertheless, both techniques showed significant improvements in the severity of symptoms and pain, in sensory nerve testing and in electro-diagnostic parameters, when comparing pre- with postoperative data after 1 year. The endoscopic approach revealed no distinct advantages over the open technique not only in the late but also in the early postoperative follow-up period when performing intra-individual comparison. Considering the higher complication rate and costs when performing 2-PER the OR with two minimised incisions seems to be a good alternative in order to keep the recovery period as short as possible.", "A 10-center randomized prospective multicenter study of endoscopic release of the carpal tunnel was carried out. Surgery was performed with a new device for transecting the transverse carpal ligament while control hands were treated with conventional open surgery. There were 122 patients in the study; 25 had carpal tunnel surgery on both hands and 97 had surgery on one hand. Of the surgical procedures, 65 were in the control group and 82 were in the device group. The endoscopic device was coupled to a fiberoptic light and a video camera. A trigger-activated blade was used to incise the transverse carpal ligament. After surgery, the best predictors of return to work and to activities of daily living were strength and tenderness variables. For patients in the device group with one affected hand, the median time for return to work was 21 1/2 days less than that for the control group. Two patients treated with the endoscopic device required reoperation by open surgical decompression; only one of these had incomplete release with the device. Two patients in the device group experienced transient ulnar neurapraxia.", "To compare the results of open with endoscopic release of the carpal tunnel in patients with the carpal tunnel syndrome.\n Randomised prospective study.\n General hospital Zeeuws-Vlaanderen, Oostburg and Terneuzen, the Netherlands.\n 178 patients were randomised for open or endoscopic release. The symptom severity score and functional status score were completed before and three months after the procedure. One week after the operation the patients' postoperative pain was measured on a 10-point visual analogue scale. Differences were analysed using the Chi-square test or the t-test.\n Randomisation failed in two patients; 85 patients had an endoscopic release and 91 patients had an open release. The postoperative pain was significantly less in the endoscopic group. Improvement in symptom severity score and functional status score was the same in both groups. There was no difference in absence from work. Two local complications occurred in the endoscopically treated group. Of the patients 25% were not or only slightly satisfied with the results.\n Endoscopic release of the carpal tunnel is as effective as the open release but it gives less postoperative pain. Because of the risk of complications and the additional costs, the endoscopic release is not the preferred method for treatment of the carpal tunnel syndrome, however.", "The authors studied two aspects of the carpal tunnel syndrome. As far as the diagnosis is concerned, clinical signs and provocative manoeuvres compared to the accepted standard of electrophysiological studies proved to be insufficient to settle a surgical indication in 85 carpal tunnel syndromes. When surgery is needed, post-operative course is frequently bothered by pillar pain and decreased strength postponing return to manual activities. The authors performed a prospective randomized study of 3 techniques in 251 carpal tunnel releases: classical technique, Agee endoscopic technique and anterior ligamentoplasty. Strength was only improved by the last technique. The only advantage for the endoscopic technique was greater post-operative comfort.", "To evaluate prospectively the safety and effectiveness of a mini-open blind technique for carpal tunnel release (group A) when compared with a limited open technique (group B).\n From November 1999 to May 2001 (mean follow-up period, 30 mo) we performed 222 carpal tunnel release procedures on 185 consecutive patients. All patients were affected by mild to moderate median nerve compression. Patients in group A (82 patients, 99 procedures) had a short transverse incision at the wrist (length, 2 cm). We used a manual surgical instrument that helps in blindly dividing the flexor retinaculum because it has an integrated light source. The light makes it possible to locate precisely the tool blade by transillumination. Patients in group B (103 patients, 123 procedures) had a limited longitudinal incision (length, 3-4 cm). The preoperative and postoperative patient statuses were evaluated with an Italian modified version of the Boston Carpal Tunnel questionnaire with a mean of 30 months' follow-up after surgery (range, 24-39 mo).\n Group A patients showed better results than group B patients in all of the sections of the Italian modified version of the Boston Carpal Tunnel questionnaire at a mean follow-up period of 19 months, whereas after a mean of 30 months of follow-up evaluation the differences between groups A and B tended to decrease. Disease recurred in 7 group B patients, whereas only 1 patient in group A experienced symptom recurrence at the latest office evaluation.\n The blind mini-invasive technique has been shown to be as safe as traditional techniques but the recovery period is significantly shortened. With the technique we described a low recurrence rate was observed. All patients in group A reported great reduction in preoperative pain and numbness.", "In order to define the role of two-portal endoscopic carpal tunnel release, a prospective randomised study with an independent observer was performed to compare endoscopic and open surgery. Thirty-two hands in 29 patients, with symptoms, clinical signs and EMG changes consistent with idiopathic carpal tunnel syndrome were randomised to either endoscopic carpal tunnel release or open release. No significant difference in sick leave between the two groups could be found, being a mean of 17 days (range 0-31 days) with endoscopic surgery, and 19 days (range 0-42 days) with open conventional surgery. No differences in surgical results were found, but three patients in the endoscopic group suffered transient numbness on the radial side of the ring finger.", "Proponents of endoscopic carpal tunnel release have been advocating the technique for more than 10 years but there is still debate about its efficacy, safety and cost-effectiveness. We have performed a randomized, prospective, blind trial to compare early outcome after single portal endoscopic or open carpal tunnel surgery and to assess the cost-effectiveness of the procedures. There were no significant differences in symptom and functional activity scores, grip strength or anterior carpal pain in the first 3 months. For those in employment, we found a statistically significant difference between the two treatment groups with the endoscopic group returning to work, on average, 8 (95% CI, 2-13 days) days sooner than the open group. This translates into a cost saving to industry. There were no major neurovascular complications in either group. On the basis of these findings, we recommend that endoscopic carpal tunnel release should be considered in the employed as a cost-effective procedure, but perhaps not in the general population as a whole.", "This prospective randomized double-blind control trial compared lengthening and simple division of the flexor retinaculum in carpal tunnel decompression. Twenty-six patients with bilateral carpal tunnel syndrome were randomly allocated to have the flexor retinaculum divided on one side and lengthened on the other. All 52 hands were reviewed at regular intervals up to 25 weeks. The patients, therapists and the final reviewer were unaware of treatment allocation. The Levine symptom and function scores were used to assess the severity of the carpal tunnel syndrome and showed that the two treatments were comparable for relief of carpal tunnel symptoms. The two treatments were also similar for function measured with the Jebsen-Taylor test. There is no identifiable benefit in lengthening the flexor retinaculum when decompressing the carpal tunnel. Moderate or severe pillar and scar pain is common, occurring in 13 of 52 hands after surgery, but only in four by the 12th week and two by the 25th week.", "To compare a limited palmar incision for carpal tunnel release (CTR) with a traditional open technique, which is still considered the gold standard.\n Seventy-two patients with a carpal tunnel syndrome were individually randomized into the trial (limited incision CTR) (n=36) and control group (traditional technique CTR) (n=36). In the trial group, skin incision parallel to the thenar crease was made up to 2.5 cm in length, under an operating microscope and endoscopic transillumination. Skin incision in the control group began at the distal border of the carpal ligament, followed the longitudinal crease of the palm, and crossed the base of the palm in a zigzag fashion. Three months after surgery, the patients were asked about symptomatic relief and intervals between the operation and return to their daily activities and work, and examined for scar tenderness and esthetic outcome. Distal motor latency, conduction velocity, scar length, scar width, and operation time were measured.\n There were no differences between the two groups in symptomatic relief and electrophysiological parameters. Intervals between the operation and return to daily activities (median 5 days, range 2-15) were shorter in the trial group than in the control group (median 10 days, range 2-21; p<0.001), as well as the intervals between the operation and return to work (median 15 days, range 5-45 vs median 30 days, range 10-60; p<0.001). Scar/pillar tenderness, scar length and width, esthetic outcome, and operation time were significantly better in the trial group.\n Limited palmar incision CTR is as effective and safe as traditional CTR technique, but with better postoperative recovery and cosmetic results.", "To define the role of two-portal endoscopic carpal-tunnel release as a method for the treatment of compression of the median nerve at the wrist, a prospective, randomized, multicenter study was performed on 169 hands in 145 patients. Either open or endoscopic carpal-tunnel release was performed in all of the patients who had clinical signs and symptoms consistent with carpal tunnel syndrome, had not responded to or had refused non-operative management, and had had electrodiagnostic studies consistent with carpal tunnel syndrome. Follow-up evaluations were performed at twenty-one, forty-two, and eighty-four days. At the end of the follow-up period, both the open and endoscopic methods had resulted in high levels of achievement of the primary outcomes (relief of pain and paresthesias). The numbness and paresthesias were relieved in eighty (98 per cent) of eighty-two hands in the open-release group compared with seventy-seven (99 per cent) of seventy-eight hands in the endoscopic-release group. This parameter was not recorded for three hands in the open-release group or six hands in the endoscopic-release group. The satisfaction of the patients with the procedure, graded on a scale of 0 to 100 per cent, averaged 84 per cent in the open-release group compared with 89 per cent in the group that had had endoscopic release. We found no significant differences between the two groups with regard to the secondary quantitative-outcome measurements, including two-point discrimination, postoperative interstitial-pressure data for the carpal canal, Semmes-Weinstein monofilament testing, and motor strength. The open technique resulted in more tenderness of the scar than did the endoscopic method. Thirty-two (39 per cent) of eighty-two hands in the open-release group and fifty (64 per cent) of seventy-eight hands in the endoscopic-release group were not tender at eighty-four days. This parameter was not recorded for three hands in the open-release group and six hands in the endoscopic-release group. The open method also resulted in a longer interval until the patient could return to work (median, twenty-eight days, compared with fourteen days for the open-release and endoscopic-release groups). Four complications occurred in the endoscopic carpal-tunnel release group: one partial transection of the superficial palmar arch, one digital-nerve contusion, one ulnar-nerve neuropraxia, and one wound hematoma.(ABSTRACT TRUNCATED AT 400 WORDS)", "Carpal tunnel syndrome is a common condition causing hand pain and numbness. Endoscopic carpal tunnel release has been demonstrated to reduce recovery time, although previous studies have raised concerns about an increased rate of complications. The purpose of this prospective, randomized study was to compare open carpal tunnel release with single-portal endoscopic carpal tunnel release.\n A prospective, randomized, multicenter center study was performed on 192 hands in 147 patients. The open method was performed in ninety-five hands in seventy-two patients, and the endoscopic method was performed in ninety-seven hands in seventy-five patients. All of the patients had clinical signs or symptoms and electrodiagnostic findings consistent with carpal tunnel syndrome and had not responded to, or had refused, nonoperative management. Follow-up evaluations with use of validated outcome instruments and quantitative measurements of grip strength, pinch strength, and hand dexterity were performed at two, four, eight, twelve, twenty-six, and fifty-two weeks after the surgery. Complications were identified. The cost of the procedures and the time until return to work were recorded and compared between the groups.\n During the first three months after surgery, the patients treated with the endoscopic method had better Carpal Tunnel Syndrome Symptom Severity Scores, better Carpal Tunnel Syndrome Functional Status Scores, and better subjective satisfaction scores. During the first three months after surgery, they also had significantly (p < 0.05) greater grip strength, pinch strength, and hand dexterity. The open technique resulted in greater scar tenderness during the first three months after surgery as well as a longer time until the patients could return to work (median, thirty-eight days compared with eighteen days after the endoscopic release). No technical problems with respect to nerve, tendon, or artery injuries were noted in either group. There was no significant difference in the rate of complications or the cost of surgery between the two groups.\n Good clinical outcomes and patient satisfaction are achieved more quickly when the endoscopic method of carpal tunnel release is used. Single-portal endoscopic surgery is a safe and effective method of treating carpal tunnel syndrome.", "We conducted a prospective, randomized study to evaluate the effect of flexor tenosynovectomy as an adjunct to open carpal tunnel release for the treatment of idiopathic carpal tunnel syndrome and reviewed the histological characteristics of the flexor tenosynovium to identify possible correlations between histopathology and symptoms.\n Eighty-eight wrists in eighty-seven patients with idiopathic carpal tunnel syndrome were randomized to open carpal tunnel release with or without flexor tenosynovectomy. A validated self-administered questionnaire for the assessment of symptom severity and functional status was completed both before and after the operation to assess patient outcome. The study group included fifteen men and seventy-two women with a mean age of fifty-eight years. All patients were followed for a minimum of twelve months after the operation. Intraoperatively, the tenosynovium of all patients was graded on the basis of its gross appearance. Half of the wrists were then treated with a flexor tenosynovectomy through the operative incision, and the tenosynovium was graded histologically. Correlations were sought between the gross appearance of the tenosynovium and the preoperative and postoperative symptoms and functional status, between the histologic appearance of the tenosynovium and the preoperative and postoperative symptoms and functional status, and between the gross and the histologic findings.\n After the operation, both groups improved significantly with respect to symptom severity and functional status (paired t test), with no significant difference between the groups (unpaired t test). No significant correlation was found between the gross appearance of the tenosynovium and the preoperative or postoperative symptoms and functional status, between the histologic appearance of the tenosynovium and the preoperative or postoperative symptoms and functional status, or between the gross and the histologic findings.\n We observed neither an added benefit nor an increased rate of morbidity in association with the performance of a flexor tenosynovectomy at the time of carpal tunnel release. We identified no clinical correlations that might predict which individuals would benefit from flexor tenosynovectomy on the basis of either the gross (intraoperative) or histologic evaluation of the flexor tenosynovium. Our findings suggest that routine flexor tenosynovectomy offers no benefit compared with sectioning of the transverse carpal ligament alone for the treatment of idiopathic carpal tunnel syndrome.", "To compare endoscopic and open carpal tunnel release surgery among employed patients with carpal tunnel syndrome.\n Randomised controlled trial at a single orthopaedic department.\n 128 employed patients aged 25-60 years with clinically diagnosed and electrophysiologically confirmed idiopathic carpal tunnel syndrome.\n The primary outcome was severity of postoperative pain in the scar or proximal palm and the degree to which pain or tenderness limits activities, each rated on a 4 point scale, transformed into a combined score of 0 (none) to 100 (severe pain or tenderness causing severe activity limitation). The secondary outcomes were length of postoperative work absence, severity of symptoms of carpal tunnel syndrome and functional status scores, SF-12 quality of life score, and hand sensation and strength (blinded examiner); follow-up at three and six weeks and three and 12 months.\n 63 patients were allocated to endoscopic surgery and 65 patients to open surgery, with no withdrawals or dropouts. Pain in the scar or proximal palm was less prevalent or severe after endoscopic surgery than after open surgery but the differences were generally small. At three months, pain in the scar or palm was reported by 33 patients (52%) in the endoscopic group and 53 patients (82%) in the open group (number needed to treat 3.4, 95% confidence interval 2.3 to 7.7) and the mean score difference for severity of pain in scar or palm and limitation of activity was 13.3 (5.3 to 21.3). No differences between the groups were found in the other outcomes. The median length of work absence after surgery was 28 days in both groups. Quality of life measures improved substantially.\n In carpal tunnel syndrome, endoscopic surgery was associated with less postoperative pain than open surgery, but the small size of the benefit and similarity in other outcomes make its cost effectiveness uncertain.", "An operative technique of carpal tunnel release using intraoperative ultrasonography is described. In this technique, \"safe line\" is defined in the transverse carpal ligament and the adjacent deep forearm fascia midway between the ulnar margin of the median nerve and the radial margin of the ulnar artery. After ultrasonographic design of a 1.0 to 1.5-cm skin incision along the safe line at the distal carpal tunnel, the distal ligament is released under direct vision. Proximal release is performed along this line under ultrasonographic monitoring using a device that consists of a basket punch and an outer metal tube. In a prospective randomized study, the outcomes were compared for carpal tunnel release using either this technique in 50 hands of 50 patients or conventional open release in 53 hands of 53 patients. Follow-up assessment at 3, 6, 13, 26, 52, and 104 weeks showed no significant difference with respect to numbness and paresthesias, static two-point discrimination, findings on Semmes-Weinstein monofilament testing, findings on manual muscle testing of the abductor pollicis brevis, and electrophysiologic findings. The ultrasonographic-release group had better outcomes regarding pain, tenderness of the scar, and key-pinch strength at 3, 6, and 13 weeks, and grip strength at 3 and 6 weeks after surgery. The scar was more aesthetic in this group. There were no complications with either technique.", "A randomized prospective study was carried out to compare one-portal endoscopic carpal tunnel release with an open procedure. There were 47 patients (mean age 52.6 years); 25 underwent an endoscopic and 22 an open release. The aim of the study was to evaluate the risks against the benefits for pain, grip, key-pinch strength and ability to return to work. The distribution of age, occupation, sex, neurographic findings and operated hand was similar in both groups. We detected no serious nerve complications. One \"open\" patient developed a hypertrophic scar, a second \"open\" patient a disabling reflex sympathetic dystrophy, one \"endo\" patient a transient neurapraxia. The remaining patients experienced complete relief of symptoms. Improvement of grip strength is significantly better after endoscopic release (P = 0.0001 at 3 months). In contrast, the key-pinch showed a similar pattern of improvement in both groups. The ability to use the operated hand as effectively as the contralateral one developed after 24 days for the endoscopic group versus 42 for the open approach (P = 0.0000). The carpal arch alteration was less important for the endoscopic group (P = 0.013), but without any correlation with the grip strength. Agee's one-portal technique only allows correct placement of a knife, not an inspection of the structures being operated upon. This is a major limitation, reducing the surgeon to a technician. Further development of this procedure demands a device that will enable a fruitful inspection of the carpal tunnel.", "The advantages and disadvantages of endoscopic compared with open carpal tunnel release are controversial. We have performed a prospective, randomised, blinded assessment in a district general hospital in order to determine if there was any demonstrable advantage in undertaking either technique. Twenty-five patients with confirmed bilateral idiopathic carpal tunnel syndrome were randomised to undergo endoscopic release by the single portal Agee technique to one hand and open release to the other. Independent preoperative and postoperative assessment was undertaken by a hand therapist who was blinded to the type of treatment. Follow-up was for 12 months. The operating time was two minutes shorter for the open technique (p < 0.005). At all stages of postoperative assessment, the endoscopic technique had no significant advantages in terms of return of muscle strength and assessment of hand function, grip strength, manual dexterity or sensation. In comparison with open release, single-portal endoscopic carpal tunnel release has a similar incidence of complications and a similar return of hand function, but is a slightly slower technique to undertake.", "We report a randomized trial of two skin incisions for carpal tunnel decompression, namely a standard incision and an ulnar L incision. We looked particularly at the resolution of local symptoms namely pillar pain and scar sensitivity. There were 47 patients in the trial. No difference was found in pillar pain between the two incisions, but one had a lower incidence of scar sensitivity. These results give a baseline for comparison of local postoperative symptoms following open release with those following endoscopic release.", "The authors compare in a prospective, randomized study the early outcome of carpal tunnel release using either a conventional palmar open release (n = 40) or a two-portal endoscopic release (n = 56). Both groups were similar. No statistically significant differences were found regarding pain, disappearing of paraesthesiae or time to return to work. However, better recovery of grip strength was observed in the endoscopic group at 1 and 3 months. No surgical complications were observed in either group.", "This prospective, randomized study compares two treatment methods in patients with primary carpal tunnel syndrome. Decompression of the transverse carpal ligament was done in thirty-two hands (thirty patients) and decompression of the transverse carpal ligament with the addition of an internal neurolysis of the median nerve was done in thirty-one hands (twenty-nine patients). Relief of symptoms was described in eighty-eight percent of the patients with carpal ligament release and eighty-one percent of patients with carpal ligament release plus internal neurolysis. Improvement in hand sensibility testing, in thenar muscle strength, and atrophy was noted in both treatment groups with no statistical difference between groups. The addition of an internal neurolysis to division of the transverse carpal ligament does not add significant improvement in the sensory or motor outcome of patients with primary carpal tunnel syndrome.", "We have performed a prospective randomized controlled trial to compare the results of open carpal tunnel release with those of carpal tunnel release using a Knifelight (Stryker, Kalamazoo, MI). This is a new knife with its own battery-powered light source which enables the operation to be performed through a small incision in the palm of the hand. There were 43 patients in the open operation group and 39 in the Knifelight group. We found no difference in discomfort reported during surgery, in the operative time, in the grip strength measured at 2 and 6 weeks post-operatively or in the proportion of patients cured of their pre-operative symptoms. Patients in the Knifelight group had a statistically significant improvement in the time to return to work and in scar tenderness at 6 weeks post-operatively." ]

[ "2289388" ]

[ "Cycle control on low-dose oral contraceptives: a comparative trial." ]

[ "Cycle control was studied comparing the monophasic oral contraceptive Loestrin with three low-dose phasic preparations (Triphasil, Ortho 10/11 and Ortho 7/7/7) in 391 women of whom 300 completed 6 cycles. Loestrin subjects had a rate of occurrence (31% of cycles) for intermenstrual bleeding (IMB) comparable to the rates for subjects on the phasic preparations (36%, 37% and 37%, respectively). Triphasil subjects had lower rates than the Ortho 10/11 and Ortho 7/7/7 subjects (p less than 0.01) in cycle one when all subjects were analyzed and in pre-study users when continuing menstrual flow (CMF) episodes were not included as IMB. IMB was a cause for dropping out of the study in 7% of subjects who were evenly distributed between groups. There were no differences between groups for BTB when perceived by subjects as a side effect. Spotting was perceived as a side effect more often with Ortho 10/11 and Ortho 7/7/7 use than with Triphasil (p less than 0.01). Loestrin, Ortho 10/11 and Ortho 7/7/7 subjects were more likely to report amenorrhea (p less than 0.001) and less likely to report leg cramps (p less than 0.01) compared to those on Triphasil. Triphasil subjects were less likely to report acne than subjects on Ortho 7/7/7 (p less than 0.01)." ]

[ "3533699" ]

[ "Randomized trial of chlorambucil for primary biliary cirrhosis." ]

[ "Twenty-four patients with primary biliary cirrhosis were entered into a prospective, randomized trial of chlorambucil therapy. Thirteen patients received chlorambucil (0.5-4 mg/day) and 11 patients received no therapy; all have been followed for 2-6 yr (mean, 4.1 yr). Two control but no treated patients died. Average serum bilirubin, serum aspartate aminotransferase activities, and albumin levels improved or remained unchanged in treated patients but worsened in controls. Serum alkaline phosphatase levels did not change in either group. Immunoglobulin M levels decreased and became normal in all treated patients but in only 3 control patients. Liver biopsy histology revealed an improvement in inflammatory cell infiltrate in treated patients in comparison with controls, but no significant change in degree of fibrosis or the histologic stage of disease. Side effects of therapy included bone marrow suppression necessitating discontinuation of the drug in 4 patients. These findings indicate that chlorambucil therapy may retard the progression of primary biliary cirrhosis. Whether such therapy will ultimately decrease morbidity and improve survival in this disease can only be demonstrated by large-scale, placebo-controlled trials." ]

[ "7575835", "10618878", "16014597", "9310515", "3505606", "1999790", "9042137", "8419896", "1399665", "10693095", "2107286", "14506534", "246352", "19830358", "3341324", "1533209", "6406888", "2357093", "12837864", "11157606" ]

[ "Effect of body position on the blood gases and ventilation volume of infants with chronic lung disease before and after feeding.", "Effects of body position on blood gases and lung mechanics of infants with chronic lung disease during tube feeding.", "Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial.", "Effect of nursing in the head elevated tilt position (15 degrees) on the incidence of bradycardic and hypoxemic episodes in preterm infants.", "The effect of body position on the respiratory rate of infants with tachypnea.", "Postural effects on pulmonary function and heart rate of preterm infants with lung disease.", "Prone positioning decreases episodes of hypoxemia in extremely low birth weight infants (1000 grams or less) with chronic lung disease.", "Pulmonary mechanics and gas exchange: effect of lateral positioning during recovery from respiratory distress syndrome.", "The effect of positioning on arterial oxygenation in children with atelectasis after cardiac surgery.", "Does supine positioning increase apnea, bradycardia, and desaturation in preterm infants?", "Effects of position changes on transcutaneous carbon dioxide tension in neonates with respiratory distress.", "[Effect of preterm infant position on weaning from mechanical ventilation].", "Positioning infants with hyaline membrane disease.", "Prone position and reduced thoracoabdominal asynchrony in preterm newborns.", "Lateral positioning of the stable ventilated very-low-birth-weight infant. Effect on transcutaneous oxygen and carbon dioxide.", "Effect of position on the mechanical interaction between the rib cage and abdomen in preterm infants.", "Postural effects on gas exchange in infants.", "Transcutaneous oxygen saturation in sleeping infants: prone and supine.", "Effect of posture on oxygenation, lung volume, and respiratory mechanics in premature infants studied before discharge.", "4A randomized trial of prolonged prone positioning in children with acute respiratory failure." ]

[ "The effect of body position before and after tube feeding was evaluated in six extremely immature infants who were being mechanically ventilated because of chronic lung disease. Their mean birthweight and gestational age were 722.7 g (range, 540 to 994) and 24.9 weeks (range, 23.9 to 26.0), respectively. This study was performed at a mean postnatal age of 47.5 days (range, 21 to 85 days). The prone position resulted in a significant increase in arterial oxygen saturation before and after feeding, whereas the tidal volume demonstrated an increase only before feeding. Also the prone position showed a significant decrease in heart rate before and after feeding and a tendency to decrease transcutaneous carbon dioxide tension values before feeding. There were no significant differences in minute ventilation despite increased tidal volume in the prone position, most likely due to a decrement of the spontaneous respiratory rate in the prone positioning. We conclude that the prone position may offer an advantage over the supine position in the management of extremely immature infants with chronic lung disease before and after feeding.", "The effects of body position and feeding on lung mechanics and blood gases in very low birthweight infants with chronic lung disease (CLD) is not fully elucidated.\n Seven very low birthweight infants who were being mechanically ventilated because of CLD were examined. They were enrolled in this study when their feeding volume exceeded 100 mL/kg per day. Each patient was kept on the same position (either prone or supine) during feeding. Feeding was given by a nasogastric tube for over 1 h every 3 h. Blood gases and lung mechanics were evaluated before, 20 min and 40 min after the initiation of the feeding and at the end of the feeding.\n The prone position resulted in a significant increase in arterial oxygen saturation during feeding. The tidal volume in the prone position was significantly larger than in the supine position only before feeding. There were no significant differences in minute ventilation between these positions during the study. Pulmonary resistance was not different in either position, but the static compliance and the work of breathing of spontaneous breaths were improved significantly when the infants were in the prone position. In the supine position, work of breathing increased and static compliance decreased significantly with time, while in the prone position, those values did not change significantly.\n The improvement in lung mechanics may partly explain better oxygenation obtained in the prone position. The prone position could decrease energy expenditure for spontaneous breathing and may shorten the period of ventilatory support for very low birthweight infants with CLD.", "In uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known.\n To test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning.\n Multicenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded.\n Patients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines.\n Ventilator-free days to day 28.\n The trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, -0.2 days; 95% CI, -3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, -3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure-free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28.\n Prone positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.", "We investigated whether nursing in the head elevated tilt position (HETP), compared with the horizontal position, has any effect on the incidence of bradycardic and hypoxemic episodes in preterm infants.\n Twelve spontaneously breathing preterm infants with idiopathic recurrent apnea were studied in a randomized controlled crossover trial. Nine infants were treated with aminophylline. Each spent a total of 24 hours in the horizontal prone position and a total of 24 hours in HETP (prone, 15 degrees). The position was changed in random order every 6 hours. Thoracic impedance, heart rate, and arterial oxygen saturation were recorded continuously. The frequency of isolated hypoxemia (arterial saturation <80%), of isolated bradycardia (heart rate <90 beats per minute), and of mixed events was analyzed and compared without knowledge of the allocated position.\n In total, there were significantly fewer bradycardic and/or hypoxemic episodes (28.2%) in HETP compared with the horizontal position (mean difference, 13.35 episodes/24 hours; 95% confidence interval [CI]: 5.9- 20.8). The decrease was largest for isolated hypoxemic episodes (48.5%; mean difference, 11.74 episodes/24 hours; 95% CI: 6.1-17.4). Isolated bradycardic episodes (mean difference, 2.27 episodes/24 hours; 95% CI: -0.78-5.31) and mixed events were not decreased significantly in HETP.\n Nursing in a moderately tilted position (15 degrees) reduces hypoxemic events in preterm infants. This intervention is easy to apply, quickly reversible, and can be combined with drugs such as aminophylline.", "In neonatal disease states where lung compliance is reduced (e.g., inadequate resorption of fetal lung fluid or, surfactant deficiency) an infant's normally low functional residual capacity (FRC) decreases even further. Tachypnea is an efficient compensatory maneuver for the newborn. We evaluated the effect of different bed and body positions on the increased respiratory rate observed in infants with transient tachypnea of the newborn (TTN), infant respiratory distress syndrome (RDS), and bronchopulmonary dysplasia (BPD). Seventeen infants were studied (TTN, n = 6; RDS, n = 6; BPD, n = 5) in four different positions: supine flat, supine elevated, prone flat, and prone elevated. Respiratory rate and heart rate were evaluated in each position. Analysis of variance for the three patient groups showed a lower respiratory rate when the bed was elevated 20-30 degrees compared to flat (P = 0.0001), in the prone posture compared to supine (P = 0.031), and no significant difference in heart rate. The lowest mean respiratory rate occurred when patients were in the prone elevated position. The significant improvement in tachypnea seen in the prone and elevated positions was likely related to improved FRC resulting from reduced cephalad stress on the diaphragm from the abdomen. Positioning neonatal patients with respiratory insufficiency was a simple and safe therapeutic maneuver with prompt and demonstrable benefit.", "nan", "Extremely low birth weight infants with chronic lung disease (CLD) have frequent episodes of desaturation (hypoxemia). We quantified oxygenation and episodes of hypoxemia in 55 infants (birth weight < or = 1000 gm) with CLD in the supine versus prone position, for 1-hour time intervals. Oxygen saturation was measured with the Nellcor N-200 pulse oximeter and a computer program. Prone positioning increased oxygen saturation from 92.0% to 94.1% (p < 0.001) and significantly decreased episodes of hypoxemia to oxygen saturation levels of less than 90%, 85%, and 80% (p < 0.001). Our findings support prone positioning for the extremely low birth weight infant with CLD in an intensive care setting.", "Sixteen stable intubated premature infants without a clinically significant patent ductus arteriosus were studied during recovery from respiratory distress syndrome in order to determine the effects of left and right lateral, as compared to supine, positioning. Pulmonary mechanics were measured for spontaneous breaths 5 and 15 minutes after positioning, and arterial blood gases 15 minutes after positioning. Infants were randomized to 1 of 2 position sequences: (1) supine, left, supine, right or (2) supine, right, supine, left. No significant differences were detected between positions for dynamic compliance, tidal volume/kg, and total, inspiratory and expiratory pulmonary resistance. Likewise, no significant differences in PaO2 or PaCO2 were detected between the positions. The sequence of positions did not affect the pulmonary mechanics of spontaneous breaths or arterial blood gases. This suggest that short-term lateral positioning as well as supine positioning can be utilized without deleterious effects on pulmonary mechanics and gas exchange in neonates recovering from respiratory distress syndrome.", "To determine the effect of body position on arterial oxygenation in children with unilateral atelectasis after cardiac surgery.\n Prospective, quasi-experimental, random assignment.\n Midwestern university-affiliated tertiary pediatric medical center.\n 25 children who underwent cardiac surgery and who presented with unilateral atelectasis within 2 weeks of operation. Age range was one month to 10 years (mean 34 months).\n The partial pressure of oxygen.\n Data collection was initiated within 24 hours of the diagnosed unilateral atelectasis. Arterial blood gases were drawn from intraarterial lines after subjects were placed for 15 minutes in the supine, right lateral, and left lateral decubitus positions (atelectatic lung dependent or nondependent), the order being randomized.\n Analysis of variance for repeated measures was used in the data analysis. The mean PaO2 for the supine, nondependent, and dependent positions were 115, 118, and 112, respectively. No statistical differences at p less than 0.05 level of significance were demonstrated for the body positions under study. Age and degree of atelectasis were analyzed as covariates to determine the possible correlation with the PaO2 and the change in PaO2. Age inversely correlated with the PaO2, r = -0.24 (p less than 0.05), indicating the older subjects had a lower PaO2. The degree of atelectasis demonstrated correlation with the change in PaO2, r = -0.26 (p less than 0.05) indicating the subjects with greater degree of atelectasis had a lesser change in PaO2.\n These results differ from similar studies on the effect of positioning in adult subjects. This finding suggests that the effect of positioning of children who have had cardiac surgery should be evaluated on an individual basis with close monitoring for changes in clinical condition and oxygen saturation and periodic arterial oxygen blood sampling until further studies can provide conclusive direction.", "The purpose of this study was to determine the effects of prone and supine positioning on the cardiorespiratory stability of preterm infants with apnea and bradycardia.\n A total of 22 preterm infants with symptomatic apnea and bradycardia (gestational age of 26.9 +/- 1.8 weeks and birth weight of 865 +/- 235 gm) were monitored for 24 hours (in four sequential 6-hour blocks) for apnea, bradycardia, and oxygen desaturation in alternating positions (prone or supine) following randomization. Postconceptional age at the time of study was 31.9 +/- 3.0 weeks. Respiratory rate, heart rate, and transcutaneous oxygen saturation were continuously monitored. All episodes of apnea (> or = 10 seconds), bradycardia (< 100 beats per minute), and oxygen desaturation (< 90%) were recorded on an event monitor. Episodes of apnea, bradycardia, and oxygen desaturation were defined as clinically significant if the following criteria were met: apnea, > or = 15 seconds; bradycardia, < 90 beats per minute; and oxygen desaturation, < 80%. All other recorded episodes were considered mild. The episodes were analyzed for statistical significance using the paired t-test.\n No significant differences (p > 0.05) in the incidence of clinically significant apnea, bradycardia, or desaturation between supine and prone positions were seen in these preterm infants.\n Our results suggest that the cardiorespiratory stability of preterm infants is not significantly compromised by supine positioning.", "Routine neonatal care includes frequent position changes. Recent research has concluded that positions other than supine may result in beneficial physiologic responses. Specifically, several studies suggest that neonates may ventilate more effectively in a prone rather than in a supine position. This study tested the hypothesis that transcutaneous carbon dioxide tension (TcPCO2) would be lower in the prone than in the supine position in neonates with respiratory distress. Fourteen ventilated infants were studied. TcPCO2 was measured and recorded in prone, supine, and right-side-lying positions for each subject. There were no statistically significant differences in mean TcPCO2 values between the three positions (F = .45; df 2,39; P = .64). The relationship between TcPCO2 and PaCO2 values was stable (r = .88) during the studies. The results indicate that changing a neonate's position does not significantly alter transcutaneous carbon dioxide tension.", "To determine the effects of prone positioning on cardiorespiratory stability and weaning outcome of preterm infants during weaning from mechanical ventilation.\n From January to December 1999, a sample of 42 preterm infants, with birthweight < 2,000 g, mechanically ventilated in the first week of life, were randomly divided, in the beginning of the weaning process, into two groups according to the position: supine position (n = 21) or prone position (n = 21). Heart rate, respiratory rate, transcutaneous oxygen saturation and ventilatory parameters were recorded every one hour. Length of the weaning process and complications were also assessed.\n In both groups the mean gestational age was 29 weeks, most of the patients presented very low birthweight and respiratory distress syndrome. The mean length of the weaning process was 2 days. There were no differences between the groups regarding respiratory rate, heart rate and transcutaneous oxygen saturation, however, oxygen desaturation episodes were more frequent in supine position (p = 0.009). Ventilatory parameters decreased faster and reintubation was less frequent in the prone group (4% versus 33%). No adverse effects of prone positioning were observed.\n These results suggest that prone position is a safe and beneficial procedure during weaning from mechanical ventilation and may contribute to weaning success in preterm infants.", "nan", "To assess the effect of prone and supine positions on breathing pattern variables, thoracoabdominal motion and peripheral oxygen saturation of hemoglobin of premature newborn infants recovering from respiratory distress syndrome, while breathing spontaneously and in rapid eye movement sleep.\n This was a quasi-experimental study. Twelve preterms weighing > 1,000 g at enrollment were studied in both positions, in random order. Respiratory inductive plethysmography was used to analyze breathing pattern (tidal volume, respiratory rate, minute ventilation, mean inspiratory flow) and thoracoabdominal motion (labored breathing index, phase relation in inspiration, phase relation in expiration, phase relation in total breath and phase angle). Pulse oximetry was used to evaluate peripheral oxygen saturation. Student's t test for paired samples or the Wilcoxon test were used for statistical analysis. Significance was set at p < 0.05.\n A total of 9,167 respiratory cycles were analyzed. The prone position was associated with significant reductions in labored breathing index (-0.84+/-0.69; p = 0.001; 95%CI -1.29 to -0.40), phase relation in inspiration (-27.36+/-17.55; p = 0.000; 95%CI -38.51 to -16.20), phase relation in expiration (-32.36+/-16.20; p = 0.000; 95%CI -42.65 to -22.06) and phase relation in total breath (-30.20+/-14.76; p = 0.000; 95%CI -39.59 to -20.82). There were no significant differences between the two positions in any of the other variables analyzed.\n The prone position resulted in a significant reduction in thoracoabdominal asynchrony, without affecting breathing pattern or peripheral oxygen saturation.", "Eighteen stable very-low-birth-weight (VLBW) mechanically ventilated infants with chronic lung disease were studied to examine the effects of right and left lateral positioning in contrast to supine positioning on transcutaneous (tc) oxygen (tcPO2) and carbon dioxide measurements (tcPCO2). The neonates were studied at a median postnatal age of 31 days (range, 17 to 57 days) and had median birth weights and gestational ages of 975 g (range, 570 to 1360 g) and 27.5 weeks (range, 24 to 30 weeks), respectively. Median fraction of inspiratory oxygen was 0.32 (range, 0.23 to 0.40). The sequence of study positions was randomly determined. Sleep state as well as tcPO2 and tcPCO2 were recorded every 30 s for five minutes. A significant difference in mean tcPO2 or tcPCO2 was not detected for any of the positions. Lateral positioning may facilitate the development of midline behavior in VLBW infants. Care givers are often reluctant to position infants in side lying, however, because of concerns that ventilation or oxygenation might be compromised. We conclude that placing the stable VLBW mechanically ventilated infant in a side-lying position has no deleterious effects on oxygenation and ventilation, as measured by tcPO2 and tcPCO2, and therefore should be encouraged.", "To determine the influence of body position on chest wall and pulmonary function, we studied the ventilatory, pulmonary mechanics, and thoracoabdominal motion profiles in 20 preterm infants recovering from respiratory disease who were positioned in both the supine and prone position. Thoracoabdominal motion was assessed from measurements of relative rib cage and abdominal movement and the calculated phase angle (an index of thoracoabdominal synchrony) of the rib and abdomen Lissajous figures. The ventilatory and pulmonary function profiles were assessed from simultaneous measurements of transpulmonary pressure, airflow, and tidal volume. The infants were studied in quiet sleep, and the order of positioning was randomized across patients. The results demonstrated no significant difference in ventilatory and pulmonary function measurements as a function of position. In contrast, there was a significant reduction (-49%) in the phase angle of the Lissajous figures and an increase (+66%) in rib cage motion in prone compared with the supine position. In addition, the degree of improvement in phase angle in the prone position was correlated to the severity of asynchrony in the supine position. We speculate that the improvement in thoracoabdominal synchrony in the prone position is related to alterations of chest wall mechanics and respiratory muscle tone mediated by a posturally related shift in the area of apposition of the diaphragm to the anterior inner rib cage wall and increase in passive tension of the muscles of the rib cage. This study suggests that the mechanical advantage associated with prone positioning may confer a useful alternative breathing pattern to the preterm infant in whom elevated respiratory work loads and respiratory musculoskeletal immaturity may predispose to respiratory failure.", "In adults with unilateral lung disease, pulmonary gas exchange is better when the patients is positioned with the good lung dependent. We studied the effects of body position on gas exchange in 10 infants with unilateral lung disease by measuring transcutaneous oxygen and carbon dioxide pressures in the supine and right and left lateral positions. We also performed krypton lung scans and measured changes in thoracic gas volumes in four of the infants. Transcutaneous oxygen pressure (mean +/- S.E.) was greater with the good lung uppermost (82 +/- 7.6 mm Hg) than with the good lung dependent (73 +/- 7 mm Hg) (P less than 0.02) or in the supine position (78 +/- 7 mm Hg). There were no changes in transcutaneous carbon dioxide pressure. The proportion of ventilation to the good lung was greater with the good lung uppermost than with the good lung dependent (P less than 0.01) or in the supine position (P less than 0.02) (64 +/- 3, 46 +/- 6, and 59 +/- 7 per cent, respectively). There were no significant changes with position in functional residual capacity, tidal volume, or dynamic lung compliance. We conclude that oxygenation in infants with unilateral lung disease is best with the good lung uppermost--the reverse of what has been observed in adults.", "Pulse oximetry was used to measure transcutaneous arterial oxygen saturation in infants aged 2 to 11 months prone and supine in quiet sleep. Groups of healthy infants (n = 34), infants with upper respiratory tract infections (n = 13), and infants with generalised moderately severe lower respiratory tract infections (n = 17) were studied. No clinically important differences were demonstrated in any of these groups, although there was a small advantage in the prone position in the group with lower respiratory tract infection. The effect of posture on infants with more severe lower respiratory tract infection and during active sleep has yet to be determined.", "To determine if the prone versus the supine posture was associated with higher oxygenation levels in prematurely born infants before discharge, whether any such effect was explained by alterations in lung volume or respiratory mechanics, and if the changes were greater in oxygen-dependent infants.\n Twenty infants (10 oxygen-dependent), median gestational age 30 (range: 27-32) weeks, were studied at a median postconceptional age of 35 weeks (range: 32-38 weeks).\n On 2 successive days, infants were studied both supine and prone; each posture was maintained for 3 hours. Oxygen saturation was continuously monitored and at the end of each 3-hour period; compliance and resistance of the respiratory system and functional residual capacity (FRC) were measured.\n Overall, the median oxygen saturation and FRC were significantly higher in the prone position; compliance of the respiratory system and resistance of the respiratory system were not significantly affected by posture. Differences in oxygen saturation and FRC were significantly higher in the prone posture in the oxygen-dependent, but not the nonoxygen-dependent infants.\n Superior oxygenation in the prone posture in oxygen-dependent premature infants studied before discharge could be explained by higher lung volumes.", "To compare the effect of the prone position (PP) vs supine position (SP) on oxygenation in children with acute respiratory failure (ARF).\n Prospective, randomized controlled trial.\n A 36-bed pediatric critical-care unit in a tertiary-care, university-based children's hospital.\n Ten children (mean [SD] age, 5 +/- 3.6 years) with ARF with a baseline oxygenation index (OI) of 22 +/- 8.5.\n Following a period of stabilization in the SP, baseline data were collected and patients were randomized to one of two groups in a two-crossover study design: group 1, supine/prone sequence; group 2, prone/supine sequence. Each position was maintained for 12 h. Lung mechanics and acute response to inhaled nitric oxide were examined in each position.\n OI was significantly better in the PP compared to the SP over the 12-h period (analysis of variance, p = 0.0016). When patients were prone, a significant improvement in OI was detected (7.9 +/- 5.3; p = 0.002); this improvement occurred early (within 2 h in 9 of 10 patients) and was sustained over the 12-h study period. Static respiratory system compliance and resistance were not significantly affected by the position change. Inhaled nitric oxide had no effect on oxygenation in either position. Urine output increased while prone, resulting in a significantly improved fluid balance (+ 6.6 +/- 15.2 mL/kg/12 h in PP vs + 18.9 +/- 13.6 mL/kg/12 h in SP; p = 0.041). No serious adverse effects were detected in the PP.\n In children with ARF, oxygenation is significantly superior in the PP than in the SP. This improvement occurs early, remains sustained for a 12-h period, and is independent of changes in lung mechanics." ]

[ "7844607", "8048390", "1709686", "10764435", "8638536", "9673754", "9069306", "11061615", "8081045", "10885603", "11773168", "9345358", "8635109", "11576265" ]

[ "Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.", "Randomized study comparing chemotherapy plus radiotherapy versus radiotherapy alone in FIGO stage IIB-III cervical carcinoma. GONO (North-West Oncologic Cooperative Group).", "A randomized trial of chemotherapy followed by pelvic radiation therapy in stage IIIB carcinoma of the cervix.", "Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer.", "The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer.", "Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies.", "Induction chemotherapy and radiotherapy of advanced cancer of the cervix: a pilot study and phase III randomized trial.", "A randomised, prospective, phase III clinical trial of primary bleomycin, ifosfamide and cisplatin (BIP) chemotherapy followed by radiotherapy versus radiotherapy alone in inoperable cancer of the cervix.", "[Neoadjuvant chemotherapy of stage IIb or III cancers of the uterine cervix. Long-term results of a multicenter randomized trial of 151 patients].", "The Scottish and Manchester randomised trial of neo-adjuvant chemotherapy for advanced cervical cancer.", "Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study.", "Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results.", "Radiotherapy and neoadjuvant chemotherapy for cervical carcinoma. A randomized multicenter study of sequential cisplatin and 5-fluorouracil and radiotherapy in advanced cervical carcinoma stage 3B and 4A.", "A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical cancer." ]

[ "Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial.\n Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy.\n Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone.\n Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.", "Between January 1989 and December 1991, 64 patients with advanced cervical carcinoma FIGO stage IIb-III were randomized to receive radiotherapy (RT) alone or the sequential combination of chemotherapy (CT) and RT. RT consisted of external RT (40 Gy fractionated over 4 weeks)+brachy-therapy (40 Gy to point A)+an additional boost to the parameters (15-20 Gy) in arm RT; CT consisted of cisplatin 60 mg/m2 i.v. day 1 q 15 days administered for 2 cycles before the start of RT and for 4 cycles after the end of radiation treatment in CT+RT arm. Among the 58 evaluable patients objective response rate was as follows: in RT arm, CR in 40.7% of patients, PR in 40.7%, and SD in 18.6%; in CT+RT arm, CR in 42% of patients, PR in 35.5%, and SD in 22.5%. The median duration of response was 12 months (range: 3-38 + months). At a median follow-up of 36 months survival (S) and progression-free survival (PFS) were 83% and 72.4% in RT arm, 72% and 59.3% in CT+RT arm, respectively. No significant difference was observed between the 2 treatment arms, neither in terms of objective response nor in terms of S and PFS. Both treatments were generally well tolerated. In our experience the addition of chemotherapy to standard radiotherapy does not enhance morbidity and does not interfere with the correct delivery of the planned treatment. However, results of this combined modality regimen remain unsatisfactory, since no improvement in pelvic control and survival of patients with advanced cervical carcinoma was observed.", "Because of the poor results in stage III B carcinoma of the cervix with standard treatment using radiotherapy alone, we designed a randomized trial to determine whether administration of chemotherapy before pelvic irradiation would improve survival. Between May 1984 and August 1986, 107 patients with previously untreated squamous cell carcinoma were randomly assigned, after stratification by age (less than 50 v greater than 50 years), extent of parametrial involvement (unilateral v bilateral), and lymphangiographic findings (negative v positive) to pelvic radiotherapy (RT; arm A) or three cycles of chemotherapy (CT; bleomycin, vincristine, mitomycin, and cisplatin [BOMP]), followed by the same radiotherapy regimen (CT + RT; arm B). The groups were balanced by age, performance status, extent of parametrial involvement, bulkiness of cervical disease, nodal involvement, and presence of hydronephrosis. Minimal follow-up is 34 months. A complete local response was observed in 32.5% of the patients in arm A and in 47% of the patients in arm B (P = .19). Overall 5-year survival rates were 39% for the RT arm and 23% for the CT + RT approach (P = .02). Toxicity was severe in arm B and included fatal pulmonary toxicity in four patients. Locoregional and distant failures were similar in both groups. We conclude that, despite a satisfactory response rate, neoadjuvant BOMP chemotherapy adversely affects survival in stage III B cervical cancer and is associated with unacceptable toxicity.", "To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer.\n Women with previously untreated bulky (primary tumor >/= 4 cm) stage IB or IIA non-small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative.\n Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival.\n NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.", "To clarify the effect of neoadjuvant intraarterial infusion chemotherapy on the cure rate in advanced cervical cancer with bulky tumor, a total of 50 patients were examined prospectively. The clinical stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification included 23 IIb, 6 IIIa, and 21 IIIb. These patients were randomly divided into the neoadjuvant intraarterial infusion chemotherapy group and the control group. There were no significant differences in mean age, FIGO clinical stage, and tumor histology between groups. Twenty-five patients in the former group were given 25 mg/m2 of cisplatin and 15 mg/m2 of bleomycin via each internal iliac artery. If the results of the evaluation indicated that surgery was feasible, radical surgery was performed. The patients whose tumors were inoperable received radiation therapy consisting of external irradiation and intracavitary irradiation. Twenty-five patients in the control group also underwent the same radiation therapy. The overall response rate was 80.0%. Eighteen of 20 responders underwent surgery. The 3-year survival rate was 85.7% for operated patients, 42.9% for patients receiving neoadjuvant intraarterial infusion chemotherapy followed by irradiation, and 49.5% for the control group. In the present study, neoadjuvant intraarterial infusion chemotherapy did not improve the prognosis of patients with advanced cervical cancer compared to radiation therapy alone, and only responders who underwent surgery obtained an advantage in survival.", "Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) 'CT-RT Group' n = 94 or RT alone, RT Group n = 90. In the 'CT-RT Group', of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged > 45 and those with Hb > 10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p < 0.01. In the 'RT Group' 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the 'CT-RT Group' and the 'RT Group' is 38% +2.01 (SE) and 36% +1.85 (SE), p = 0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the 'CT-RT Group' 29 patients responded; CR-8 (22.2%), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT-24 of 35 (68-6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the 'RT Group'-21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71% in the 'CT-RT Group' and 69% in the 'RT Group', p = ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity-two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.", "This study assessed the effectiveness and toxicity of induction chemotherapy (CT) and radiation therapy (RT) in the treatment of locally advanced carcinoma of the cervix with data provided by a pilot study and a randomized trial.\n Eighty-six patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB-IVA (Stage IB >4-cm tumor diameter) (Group A) were entered in a pilot study and treated with cisplatin (50 mg/m2), vincristine (1 mg/m2 on days 1, 11, and 21), bleomycin (25 mg/m2 infusion on days 1-3, 11-13, and 21-23), and standard RT. Ninety-six patients were randomized to either this same CT regimen and RT, or RT alone (Group B: CT plus RT or RT).\n In Group A, 58% responded to induction CT. With a mean follow-up of 78 months, 73% achieved pelvic control (LRC), and 55% were disease-free survivors. Response to CT was not a marker for ultimate LRC or increased disease-free survival (DFS). In Group B, 62% responded to CT. With a mean follow-up of 43 months, LRC was 68% and 65% for all randomized patients in the CT plus RT and RT arms, respectively (p = NS). In patients who completed treatment, 78% and 70%, respectively, achieved LRC (p = NS). Disease-free survival rates were 38% and 49% for randomized patients in the CT plus RT and RT arms (p = NS), respectively, and 44% and 52% in those patients completing treatment (p = NS), respectively. Complications were acceptable.\n Data from this study did not prove the efficacy of induction CT before definitive RT in locally advanced cancer of the cervix. Induction CT with the currently used combinations and modes of administration should not be considered standard therapy.", "Phase II studies have shown primary (neo-adjuvant) chemotherapy with bleomycin, ifosfamide and cisplatin (BIP) is active against inoperable cervical cancer. We present here results of a randomised phase III multicentre trial comparing radical radiotherapy with neo-adjuvant BIP chemotherapy followed by radical radiotherapy in patients with inoperable cervical cancer, designed to discover whether this combination might improve survival.\n Patients with inoperable cervical carcinoma were randomised to pelvic radiotherapy alone [RT] or two to three cycles of bleomycin 30 units/24-hour infusion, ifosfamide 5 g/m2/24 hours, and cisplatin 50 mg/m2) chemotherapy followed by pelvic radiotherapy (BIP + RT). Randomisation was stratified by stage and radiotherapy centre.\n One hundred seventy-two eligible women were randomised into this trial; eighty-six to RT and eighty-six to BIP + RT. A total of 190 cycles of chemotherapy were given. Median follow-up for the 47 patients still alive is 9 years with a minimum follow-up of 3 years. Complete or partial response occurred in 51 of 86 (59%) of those randomised to RT and 60 of 86 (69%) of those randomised to BIP + RT. The difference between response rates does not reach statistical significance (chi2 = 2.06, P = 0.15). Median survival is two years with an actuarial survival at five years of 32% (95% confidence interval (95% CI): 25%-39%). There is no significant difference between the treatment groups (chi2log-rank = 0.11, P = 0.74).\n This study does not show any survival benefit from the use of neo-adjuvant BIP chemotherapy in advanced cervical cancer.", "Present chemotherapy, with cisplatin combinations, currently offers the possibility of seeking adjuvant therapy in locally advanced and bulky carcinomas of the cervix, which have an unfavorable prognosis (nodal involvement). This initial adjuvant chemotherapy may improve the results of classical pelvic irradiation. From 1982 to 1987, a randomized phase III trial was performed in order to determine the long term effect of induction chemotherapy before irradiation in stage IIb-N1, III, M0 squamous cell carcinomas of the cervix. Radiotherapy (R) for all patients consisted in 50 Gy in the pelvis with a boost by external irradiation of the brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen (C + R group) was an association of methotrexate, chlorambucil, vincristine and cisplatin, given every 3 weeks, at least two courses were to be given before assessing efficacy and two more courses were given to patients who responded. After a follow up of 5-10 years, 76 patients were fully evaluable in the R arm and 75 in the C + R arm. The response rate (> 50%) to chemotherapy was 42.5% and after completion of treatment, remission rate was 93% in the R arm and 96% in the C + R arm. The disease-free survival was 40% in the C + R group and 35% in the R group, and the median survival was 42 and 45 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group when they are responding to chemotherapy, than in R group (P < 0.05). Radiotherapy was not modified whether patients had an initial chemotherapy or not; tolerance was not significantly different between the two groups. Efficacy of induction chemotherapy is an available test for long term results. This approach has the potential for improving the outlook in patients with high-risk primary cancer: earlier use and higher dose intensity of chemotherapy may be associated with a better cytoreduction, and probably a better survival. Further controlled investigations are warranted to confirm the value of adjuvant chemotherapy in cervical cancer.", "204 eligible patients were entered into a multicentre randomised trial of neo-adjuvant chemotherapy prior to radical radiotherapy. The aim of this study was to assess whether there was any survival advantage in patients undergoing chemotherapy and radiotherapy compared with those given radiotherapy alone. Patients were aged up to 70 years, performance status 0-1/2, with bulky stage IIb, stage III or stage IVa squamous or adenosquamous carcinoma. Three cycles of methotrexate 100 mg/m2 and cisplatin 50 mg/m2 were given at 2-weekly intervals before radical radiotherapy. 104 eligible patients received the combination treatment and 100 radiotherapy only. The two arms of the study were well balanced for tumour and patient characteristics. The response rate to chemotherapy was 49%, 33% of patients in the radiotherapy (XRT) alone arm and 45% of the combination arm were clinically free of tumour at the end of treatment. The median follow-up for surviving patients is 5.4 years (range: 11 months-8 years) and 84% have been followed-up for more than 4 years. 134 patients have died (68 XRT only, 66 combined arm). The median survival RT alone was 111 weeks (95% confidence interval (CI) 72-151 weeks), combination arm 125 weeks (95% CI 79-170 weeks). The estimated death ratio is 0.79 (P = 0.19, 95% CI 0.56-1.12). The estimated 3-year survival is 40% (95% CI 30-50%) RT only compared with 47% (95% CI 37-57%) in the combination arm. Acute and late toxicity of radiotherapy was not increased by the addition of chemotherapy.", "Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity.\n Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B).\n Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P =.007 and P =.02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P =.005 andP =.02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P =.36 and P =.29), respectively. Treatment had a significant impact on OS and PFS.\n Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT.", "To determine if three courses consisting of 50 mg/m2 cis-platinum, 1 mg/m2 vincristine, and 25 mg/m2 bleomycin (day 1-3) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy.\n Two hundred five unselected stage Ib patients (having tumors > 2 cm in diameter) were divided into two groups at random: (1) The group control consisted of 103 patients (56 bulky, > 4 cm diameter) treated with Wertheim-Meigs (if the tumor was resectable with free surgical margins) + adjuvant radiotherapy to whole pelvis (extended field radiation was used only in patients with paraaortic lymph node metastases). When the tumor was unresectable, a surgical staging was performed and radiotherapy was the chosen treatment. (2) Neoadjuvant (102 patients, 61 bulky) had neoadjuvant chemotherapy and then the same treatment as the control patients.\n After 67 (31-102) months of follow-up, no difference was seen in tumors > 2 and < 4 cm in both groups (C = 77% vs N = 82%), but statistically significant differences were seen in survival and disease-free survival, in bulky tumors, and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy (80%) and the control (61%). This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group (61/61, 100%) vs control (48/56, 85%; P < 0.01). After 7 years of follow-up, the outcome of the unresectable bulky control group of patients is significantly worse (14%) than that of the resectable group (69%; P < 0.001). With regard to recurrences, a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed (P < 0.001). Survival was improved in bulky resectable cases (N = 81% vs C = 69%, P < 0.05). Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases, tumor bulk, and vascular embolism had been decreased (P < 0.001).\n Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected, bulky (> 4 cm diameter) stage Ib patients.", "The locoregional failure rate remains high in advanced cervical carcinoma. Chemotherapy (CT) was added to radiotherapy (RT) in order to increase disease control and to improve 5-year survival.\n CT + RT included cisplatin administered 100mg/m2, d.1 plus 5-fluorouracil 1000 mg/m2 D.1 to 5, ci (120 hrs), q every 3rd week for 3 cycles, followed by RT. RT included external beam irradiation 64.8 Gy in 1.8 Gy fractions, five days a week, by 4-field box technique. The median follow-up was 46 months. Ninety-four patients were evaluable for survival, 47 in the CT + RT group and 47 in the RT group. Ninety-two patients were evaluable for response. Known prognostic factors were equally distributed between the two groups.\n Of the 43 patients evaluable before RT, 31 (72%) achieved a partial or complete response after CT alone. After RT, 52 patients attained a complete response, 25 in the CT + RT group and 27 in the RT-group. Sixty-three patients developed distant metastases or local relapse, 30 in the CT + RT group and 33 in the RT group. In the CT + RT group 6 of the 9 patients with metastases also had local progression at relapse, in the RT group, 7 of 17 patients. The survival rates for the two groups are not statistically different. Thirty-seven patients are alive, 29 have no evidence of disease. Fifty-seven have died, 29 in the CT + RT group and 28 in the RT group. Fifty-four deaths were related to cancer, and 3 to therapy.\n Sequential CT and RT did not improve the survival, local control, or metastasis rate compared with RT alone.", "Seventy-one patients with stage IIb-IVa cervical cancer were entered on a randomized trial comparing standard pelvic radiotherapy vs. 3 cycles of combination chemotherapy with cisplatin, vinblastine and bleomycin followed by pelvic radiotherapy. Four out of 34 patients randomized to PVB followed by radiotherapy received no PVB and a further 3 patients had only one or 2 cycles of chemotherapy prior to radiotherapy due to drug-related toxicity or progressive disease. After a median follow-up of 3.1 years, no significant difference in survival has emerged between the two randomized groups. However, a difference in the pattern of relapse is emerging with a relatively reduced frequency of systemic relapse in patients receiving chemotherapy prior to local radiotherapy compared to radiotherapy alone. Tumor response was seen following PVB treatment and prior to radiotherapy in 47% of patients. Overall the tumor response rate following completion of radiotherapy was 89% in those treated by radiotherapy and 94% after PVB+radiotherapy. Thirty-three percent of patients randomized to radiotherapy alone relapsed first at a distant (extra pelvic site), and only 18% of patients randomized to initial PVB followed by radiotherapy relapsed systemically initially. When results are presented according to treatment actually given, these trends in patterns of treatment failure are magnified. No treatment-related deaths were reported, and there was no excess of complications with pelvic radiotherapy in the group who had received prior PVB chemotherapy." ]

[ "19959339", "19941696", "20389255", "20555312", "20473057", "21092748" ]

[ "Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study.", "Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study.", "Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study.", "A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia.", "A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia.", "A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia." ]

[ "We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia.\n Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score < 120) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week, open-label phase. Patients received the first 2 intramuscular injections of paliperidone palmitate (50mg eq) one-week apart, then subsequent injections (25, 50, or 100mg eq, flexibly-dosed), once-monthly. Stable patients (PANSS total score < or = 75) continued into the 24-week maintenance phase. At maintenance phase endpoint, stabilized patients were randomized (1:1 ratio) to either continue paliperidone palmitate (at stabilized dose) or begin placebo in the variable-duration, double-blind phase.\n The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored paliperidone palmitate (p<0.0001, log-rank test) at interim and final analysis (n=408). The hazard ratio (placebo/paliperidone palmitate) at the final analysis was 3.60 (95% CI: 2.45, 5.28). Treatment-emergent adverse event rates (final analysis set) were: 67% for transition and maintenance phases, and 45% (placebo) and 44% (paliperidone palmitate) for the double-blind phase. Across phases, the incidence of glucose-related adverse events was low (< or = 4%), while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients. Injection site tolerability was comparable between groups.\n Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals.\n 2009 Elsevier B.V. All rights reserved.", "We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate (PP) in the treatment of schizophrenia. Patients were randomized to receive gluteal injections of placebo or PP (50 or 100 mg eq., fixed doses), without oral supplementation, on days 1, 8, and 36 (9-wk, double-blind phase) in this phase 2b study. Patients (n=197, intent-to-treat analysis set) were 62% men, mean (s.d.) age 39 (10) yr, with a baseline mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total score of 87.0 (12.5). Mean (s.d.) PANSS total scores showed significant improvement at endpoint (primary measure) for both the PP 50 mg eq. [-5.2 (21.5)] and PP 100 mg eq. [-7.8 (19.4)] groups, vs. placebo [6.2 (18.3)] (p0.001, each dose vs. placebo). This improvement was detected by day 8 and maintained to endpoint (p0.011) for both doses. In the safety analysis set (n=247), fewer PP-treated patients (2%) discontinued for treatment-emergent adverse events vs. placebo-treated (10%). Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo, with the exception of parkinsonism-related disorders (50 mg eq. 5%, 100 mg eq. 8%, placebo 1%). Results of other safety measures suggest PP to be generally well-tolerated. Throughout the study, investigators rated injection-site pain as absent (56-71%), mild (24-39%), moderate (2-12%), or severe (0-2%). PP (50 and 100 mg eq. doses) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia.", "This 13-week, double-blind study evaluated the efficacy and safety of the atypical antipsychotic paliperidone palmitate (recently approved in the United States) versus placebo administered as monthly gluteal injections (after two initial doses given 1 week apart) in acutely symptomatic patients with schizophrenia. Patients (N=388) were randomly assigned (1 : 1 : 1 : 1) to paliperidone palmitate 50, 100, or 150 mg eq. or placebo. As the 150 mg eq. dose was administered to fewer patients (n=30) than planned, meaningful and definitive conclusions cannot be drawn from the results of this group. The change from baseline in Positive and Negative Syndrome Scale total score at endpoint showed improvement in both paliperidone palmitate 50 and 100 mg eq. groups but was significant only in the 100 mg eq. group (P=0.019). The paliperidone palmitate 50 (P=0.004) and 100 mg eq. (P<0.001) groups showed significant improvement in the Personal and Social Performance score from baseline to endpoint versus placebo. Common adverse events (in >or=2% of patients in any group) more frequent with paliperidone palmitate 50 or 100 mg eq. than placebo (>or=5% difference) were headache, vomiting, extremity pain, and injection site pain. Treatment with paliperidone palmitate (100 mg eq.) was efficacious and all doses tested were tolerable.", "Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p< or =0.006) and PANSS negative and positive symptom Marder factor scores (p< or =0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5-6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.", "This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or gluteal [corrected] on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P < or = 0.034) in all the paliperidone palmitate dose-groups versus placebo. Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle. Common treatment-emergent adverse events (> or =2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with > or =1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia.", "This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or 100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25mg), days 36, 50 (25 or 37.5mg) and days 64, 78 (25, 37.5 or 50mg). RIS-LAI-treated patients received oral supplementation with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n=1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (-18.6 [15.45]) and RIS-LAI (-17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [-1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings.\n Copyright © 2010 Elsevier Inc. All rights reserved." ]

[ "11229858", "7778148", "8560525", "20595477", "1951871", "18503714", "21631932", "9291905", "14640494" ]

[ "Effect of antipyretic drugs in children with malaria.", "Fever in uncomplicated Plasmodium falciparum infection: effects of quinine and paracetamol.", "Fever in uncomplicated Plasmodium falciparum malaria: randomized double-'blind' comparison of ibuprofen and paracetamol treatment.", "Intravenous ibuprofen (IV-ibuprofen) controls fever effectively in adults with acute uncomplicated Plasmodium falciparum malaria but prolongs parasitemia.", "Neither heparin nor acetylsalicylic acid influence the clinical course in human Plasmodium falciparum malaria: a prospective randomized study.", "Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial.", "Paracetamol versus placebo in treatment of non-severe malaria in children in Guinea-Bissau: a randomized controlled trial.", "Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria.", "Antipyretic, parasitologic, and immunologic effects of combining sulfadoxine/pyrimethamine with chloroquine or paracetamol for treating uncomplicated Plasmodium falciparum malaria." ]

[ "A comparison of different antipyretics in children with malaria showed a small effect of naproxen, but not of metamizol, on the reduction of fever peaks. Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria.", "The effects of quinine and paracetamol on fever were studied in 21 adult patients with acute uncomplicated falciparum malaria. Quinine alone (n = 7) had no significant effect on fever, whereas paracetamol given 2 h after quinine (n = 7) or 2 h before quinine (n = 7) reduced temperature by a mean of 2.1 degrees C (standard deviation [SD] 0.95) and 2.1 degrees C (SD 0.79) respectively. A temperature reduction of 1 degree C was associated with a mean decrement of 9.7 beats/min (SD 3.3) in the pulse rate. Quinine does not possess useful antipyretic activity.", "Fever almost invariably accompanies uncomplicated falciparum malaria. In a randomized, double-'blind' study, we compared a single dose of ibuprofen (10 mg/kg, n = 8) with paracetamol (15 mg/kg, n = 8) for the treatment of fever > 38.5 degrees C due to uncomplicated falciparum malaria. Ibuprofen was significantly more effective than paracetamol in lowering temperatures throughout the first 4.5 h after dosing (P = 0.016) and should be considered as an antipyretic agent in the management of uncomplicated falciparum infections, providing there is no contraindication to its use.", "Because some febrile patients are unable to swallow or retain oral antipyretic drugs, we carried out a double-blind, placebo-controlled trial in which intravenous ibuprofen (IV-ibuprofen) was given to adults hospitalized with fever associated with acute uncomplicated falciparum malaria treated with oral artesunate plus mefloquine. Thirty patients received IV-ibuprofen 400 mg and 30 received placebo every 6 hours for 72 hours. Reduction in the area above 37.0 degrees C versus time curve was significantly greater for IV-ibuprofen than for placebo during the first 72 hours after first administration. No patients developed severe malaria; parasite clearance was delayed in the patients whose fevers were controlled by IV-ibuprofen (median 37.3 hours versus 23.7 hours in the placebo group [P = 0.0024]). This difference did not appear to be clinically important Adverse events, none considered severe, occurred equally in both groups. IV-ibuprofen was effective and well tolerated in reducing fever in febrile inpatients with malaria.", "Procoagulant alterations and thrombocytopenia in falciparum malaria correlate with parasitemia, serum levels of tumor necrosis factor alpha (TNF alpha), and clinical severity. Thus, heparin or acetylsalicylic acid (ASA), which are used frequently to prevent thrombosis and (in the case of ASA) to control fever, could be potentially beneficial. We randomized 97 patients with falciparum malaria into three groups: 33 patients received low-dose heparin subcutaneously, 31 received ASA intravenously, and 33 did not receive either drug. All patients received appropriate antiparasitic treatment. Eighteen of 97 patients (seven receiving heparin, five receiving ASA, and 6 in the control group) had complications upon admission. During therapy, elevated TNF alpha and lactate dehydrogenase levels and decreased platelet counts returned to normal values. Except for a minimal partial thromboplastin time prolongation with heparin, heparin or ASA did not affect any laboratory parameter, duration of parasitemia, fever clearance, or the length of hospitalization. Thus, it appears that ASA and heparin do not influence the course of falciparum malaria. Hence, in view of possible side effects, these substances should not be recommended for routine use in the treatment of human malaria.", "Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed.\n Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients \"received\" mechanical treatment when the temperature rose above 37.5 degrees C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo.\n The fever clearance time using a fever threshold of 37.5 degrees C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8 degrees C or 38.0 degrees C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group.\n Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold.\n The trial registration number is: NCT00167713.", "The current guidelines for treatment of malaria include paracetamol to children with fever. No convincing evidence for the beneficial effects of this practice exists. Studies show that time to parasite clearance is significantly longer in children treated with paracetamol, which questions the policy. Whether this is of clinical importance has not been investigated.\n Children with Plasmodium falciparum monoinfection and ≥20 parasites per 200 leucocytes at the Bandim Health Centre, Guinea-Bissau were randomized to receive paracetamol or placebo together with chloroquine for three days in a double blind randomized study. Temperature and symptoms were recorded twice daily during treatment and on day 3. The participants were interviewed and a malaria film taken once weekly until day 35. The data is in the form of grouped failure-times, the outcome of interest being time until parasitaemia during follow-up. Mantel-Haenszel weighted odds ratios are given. Other differences between and within the two groups have been tested using the Chi-square test and Mann-Whitney U test.\n In the evening of the day of inclusion, the temperature was slightly, but statistically insignificant, higher in the placebo group and significantly more children complained of headache. At no other time was a significant difference in temperature or symptoms detected. However, 6 children from the placebo-group as compared to two children from the paracetamol-group were admitted to hospital with high fever and convulsions by day 3. No differences in the cumulative percentages of children with adequate clinical and parasitological response were found in the intention-to-treat analysis or in the per-protocol analysis.\n Fewer children had early treatment failure and the mean temperature was slightly lower in the afternoon on day 0 in the paracetamol group. However, the cumulative adequate clinical and parasitological cure rates were not significantly different during the period of study. It is doubtful whether adding paracetamol to the treatment of uncomplicated malaria in children is beneficial.\n NCT00137566.", "Routine antipyretic therapy in children with infectious diseases has long been the source of controversy. Each year, in addition to antimalarial medication, millions of children with Plasmodium falciparum malaria receive paracetamol to reduce fever. However, the usefulness of this practice has not been proven.\n In a randomised trial in Lambaréné, Gabon, 50 children with P falciparum malaria were treated with intravenous quinine, and received either mechanical antipyresis alone, or in combination with paracetamol. Rectal body temperature and parasitaemia were recorded every 6 h for 4 days. Plasma concentrations and inducible concentrations of tumour necrosis factor (TNF) and interleukin-6 were measured every 24 h. In addition, production of oxygen radicals was measured in both groups.\n The mean fever clearance time was 32 h for children treated with paracetamol and 43 h for those who received mechanical antipyresis alone; however, this 11 h difference was not significant (95% CI -2 to 24 h; p = 0.176). Parasite clearance time was significantly prolonged in patients who received paracetamol with a difference of 16 h (8-24 h; p = 0.004). Plasma concentrations of TNF and interleukin-6 were similar in both groups during the study. However, the induced concentrations of TNF, and the production of oxygen radicals, were significantly lower in children treated with paracetamol than those who received mechanical antipyresis alone.\n These data suggest that paracetamol has no antipyretic benefits over mechanical antipyresis alone in P falciparum malaria. Moreover, paracetamol prolongs parasite clearance time, possibly by decreased production of TNF and oxygen radicals.", "Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance. However, chloroquine may have a beneficial antipyretic effect. We therefore compared the combination of SP plus chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children (1-4 years old) in a randomized trial. Outcome variables were axillary temperatures every six hours, daily parasitemias, and serum levels of IgG antibodies to P. falciparum. Lower mean temperatures (6-48 hours) were achieved with SP plus chloroquine or paracetamol than with SP alone (P < 0.001) or chloroquine alone (P < 0.05). All three SP-treated groups showed high and similar parasite reduction (0-48 hours), whereas treatment with chloroquine alone was much less effective. Levels of IgG antibodies to P. falciparum increased significantly (P < 0.001) and similarly in the four treatment groups between days 0, 2, and 3. Thus, the addition of chloroquine or paracetamol to SP improved the clinical outcome, but did not affect the parasitologic response or antibody production." ]

[ "12066939", "1497047", "7654647" ]

[ "A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.", "Maternal hyperoxygenation in the treatment of intrauterine growth retardation.", "A prospective randomised comparison of the effect of continuous O2 therapy and bedrest on fetuses with absent end-diastolic flow on umbilical artery Doppler waveform analysis." ]

[ "To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.\n A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.\n A tertiary referral hospital in South Africa.\n Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.\n After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.\n Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.\n There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).\n This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.", "In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated.\n Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery.\n Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively.\n Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.", "nan" ]

[ "17265030" ]

[ "High-dose intravenous methylprednisolone in recent traumatic optic neuropathy; a randomized double-masked placebo-controlled clinical trial." ]

[ "To compare the effect of high-dose intravenous corticosteroid therapy with placebo in the treatment of recent traumatic optic neuropathy (TON).\n In a double-masked placebo-controlled clinical trial, 31 eyes of 31 patients were randomly assigned to two groups. Patients with history of trauma < or =7 days were included. Unconscious patients, eyes with penetrating trauma and candidates for decompression surgery were excluded. The treatment group (16 eyes) received 250 mg methylprednisolone intravenously every 6 h for 3 days, then 1 mg/kg prednisolone orally for 14 days; the placebo group (15 eyes) received 50 ml normal saline intravenously every 6 h for 3 days, then placebo for 14 days. Visual improvement was considered as a decrease of at least 0.4 logMAR in final visual acuity.\n Mean final BCVA (best corrected visual acuity) in the treatment group was 1.11+/- 1.14 and the placebo group was 1.78 +/- 1.23. This difference was not significant (P = 0.13). Visual acuity was improved in 68.8% of the treatment group and 53.3% of the placebo group, but the difference was not statistically significant (P = 0.38). The difference between initial and final BCVA in both groups was determined to be statistically significant (P < 0.001 and 0.010 respectively).\n Our study confirms earlier findings that there is no difference in visual acuity improvement between intravenous high-dose corticosteroids and placebo in treatment of recent TNO." ]

[ "16882592", "16813473", "8130287", "16011060", "15905654", "12971708", "11950019", "2181127", "15650833", "11642642" ]

[ "The effect of balneotherapy on patients with ankylosing spondylitis.", "Effects of a multimodal exercise program for people with ankylosing spondylitis.", "Is group physical therapy superior to individualized therapy in ankylosing spondylitis? A randomized controlled trial.", "Spa therapy for ankylosing spondylltis at the Dead Sea.", "Two exercise interventions for the management of patients with ankylosing spondylitis: a randomized controlled trial.", "The effectiveness of intensive group exercise on patients with ankylosing spondylitis.", "The effect of a home based exercise intervention package on outcome in ankylosing spondylitis: a randomized controlled trial.", "The effects of comprehensive home physiotherapy and supervision on patients with ankylosing spondylitis--a randomized controlled trial.", "Effects of home-based daily exercise therapy on joint mobility, daily activity, pain, and depression in patients with ankylosing spondylitis.", "Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial." ]

[ "To compare the effect of balneotherapy on physical activity and quality of life as well as the symptoms of pain and stiffness with exercise alone in ankylosing spondylitis (AS) patients.\n A total of 60 patients who had a diagnosis of AS according to the modified New York criteria were included in the study. The patients were randomly assigned to two groups. In Group I (n = 30) the patients received balneotherapy in a therapeutic pool for 30 min once a day for 3 weeks. All patients received instructions on the exercise programme, which they were requested to repeat once a day for 30 min during the study. The patients in this group continued the same exercise programme after the end of the balneotherapy protocol to complete a course of 6 months. In Group II the patients were given the same exercise protocol but did not receive balneotherapy. Patients were evaluated before the start of the study and at 3 weeks and 24 weeks. Evaluation parameters were daily and night pain, morning stiffness, the patient's global evaluation and the physician's global evaluation (according to a scoring system of 1 to 5), the Bath Ankylosing Spondilitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Dougados Functional Index (DFI), tragus-wall distance, chest expansion, modified Shober test (MST), fingertip-fibula head distance, and Nottingham Health Profile (NHP).\n Evaluations were completed in 54 patients in the two groups. Comparison of the groups showed significantly superior results for Group I for parameters of BASDAI, NHP total, pain, physical activity, tiredness and sleep score, patient's global evaluation and the physician's global evaluation at 3 weeks, but only for the parameters of patient's global evaluation and MST at 24 weeks.\n Balneotherapy has a supplementary effect on improvement in disease activity and functional parameters in AS patients immediately after the treatment period. However, in the light of our medium-term evaluation results, we suggest that further research is needed to assess the role of balneotherapy applied for longer durations in AS patients.", "Few randomized controlled studies have examined the effects of exercise in patients with ankylosing spondylitis (AS). This study investigated the effects of a 12-week, multimodal exercise program in patients with AS.\n A convenience sample of 30 patients with AS (18 male, 12 female), with a mean age of 34.9 years (SD=6.28), participated in the study. Twenty-six subjects were classified as having stage I AS and 4 subjects were classified as having stage II AS according to the modified New York Criteria.\n This study was a randomized controlled trial. Subjects were assigned to either a group that received an exercise program or to a control group. The exercise program consisted of 50 minutes of multimodal exercise, including aerobic, stretching, and pulmonary exercises, 3 times a week for 3 months. Subjects in both groups received medical treatment for AS, but the exercise group received the exercise program in addition to the medical treatment. All subjects received a physical examination at baseline and at 12 weeks. The examinations were conducted under the supervision of a physician who specialized in physical medicine and rehabilitation and included the assessment of spinal mobility using 2 methods: clinical measurements (chin-to-chest distance, Modified Schober Flexion Test, occiput-to-wall distance, finger-to-floor distance, and chest expansion) and inclinometer measurements (gross hip flexion, gross lumbar flexion, and gross thoracic flexion). In addition, vital capacity was measured by a physiologist, and physical work capacity was evaluated by a doctorally prepared exercise instructor.\n The measurements of the exercise group for chest expansion, chin-to-chest distance, Modified Schober Flexion Test, and occiput-to-wall distance were significantly better than those of the control group after the 3-month exercise period. The spinal movements of the exercise group improved significantly at the end of exercise program, but those of the control group showed no significant change. In addition, the results showed that the posttraining value of gross thoracic flexion of the exercise group was significantly higher than that of the control group. Physical work capacity and vital capacity values improved in the exercise group but decreased in the control group.\n In this study, a multimodal exercise program including aerobic, stretching, and pulmonary exercises provided in conjunction with routine medical management yielded greater improvements in spinal mobility, work capacity, and chest expansion.", "To study the effects of adding supervised group physical therapy to unsupervised individualized therapy in ankylosing spondylitis.\n One hundred forty-four patients were randomized to exercises at home, or the same plus weekly group physical therapy for 9 months. Endpoints were spinal mobility, fitness (maximum work capacity by ergometry), functioning (Sickness Impact Profile, Health Assessment Questionnaire for the Spondylarthropathies, and Functional Index), and patient's global assessment of change on a 10-cm visual analogue scale.\n Thoracolumbar flexion and extension increased by an average of 0.5 cm (9%) after home exercises, and by 0.9 cm (16%) after group therapy. Maximum load in ergometry decreased by 2 W (1%) after home exercises, but increased by 7 W (4%) after group therapy. Global assessment improved by 0.3 (6%) after home exercises, and by 1.7 (34%) after group therapy. These three differences were statistically significant. There were no significant differences in chest expansion, cervical rotation, or the self-assessments of functioning.\n Group physical therapy proved superior to individualized therapy in improving thoracolumbar mobility and fitness, and had an important effect on global health reported by the patients.", "The efficacy of spa therapy in ankylosing spondylitis has not been investigated extensively.\n To study the efficacy of balneotherapy and climatic therapy (climatotherapy) at the Dead Sea area in patients with ankylosing spondylitis.\n In a single-blind randomized controlled study, 28 patients suffering from ankylosing spondylitis were allocated into two groups of 14 patients each. The first group (the combined treatment group) received balneotherapy (mud packs and sulfur pool) and exposure to the unique climatic conditions of the Dead Sea. The second group (the climatotherapy group) used the fresh water pool and experienced the same climatic conditions. The duration of treatment was 2 weeks and the follow-up period 3 months.\n For both patient groups a significant improvement was found in the outcome measures: Bath AS Disease Activity Index (P = 0.002), VisuarAnalog Scale for pain (P = 0.002) and VAS for spinal movement (P = 0.011). The variability was explained by the effect of time (within group effect) rather than the type of treatment (between group effect). Quality of life, assessed by the SF-36 questionnaire, was very low prior to the study, but improved in terms of pain amelioration in the combined treatment group.\n Climatotherapy at the Dead Sea area can improve the condition of patients suffering from long-standing ankylosing spondylitis.", "The purpose of this clinical trial was to evaluate the impact of a 4-month comprehensive protocol of strengthening and flexibility exercises developed by our research group versus conventional exercises for patients with Ankylosing Spondylitis (AS) on functional and mobility outcomes.\n Randomized controlled trial. Forty-five patients diagnosed with AS according to the modified criteria of New York were allocated to control or experimental groups using a random numbers table. The control group was treated with a conventional protocol of physical therapy in AS, whereas the experimental group was treated with the protocol suggested by our research group. The conventional intervention consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the shortened muscles; and chest expansion exercises. The experimental protocol is based on the postural affectation of the AS and the treatment of the shortened muscle chains in these patients according to the Global Posture Reeducation (GPR) method. This intervention employs specific strengthening and flexibility exercises in which the shortened muscle chains are stretched and strengthened. The study lasted 4 mos. During this period, patients received a weekly group session managed by an experienced physiotherapist. Each session lasted an hour, and there were 15 total sessions. Changes in activity, mobility, and functional capacity were evaluated by an assessor blinded to the intervention, using the following previously validated scores from the Bath group: BASMI (tragus to wall distance, modified Schober test, cervical rotation, lumbar side flexion, and intermalleolar distance), BASDAI (The Bath Ankylosing Spondylitis Disease Activity Index), and BASFI (The Bath Ankylosing Spondylitis Functional Index).\n Both groups showed an improvement (prepost scores) in all the outcome measures, mobility measures of the BASMI index, as well as in BASFI and BASDAI indexes. In the control group, the improvement in tragus to wall distance (P=0.009) and in lumbar side flexion (P=0.02) was statistically significant. Although the rest of the outcomes also improved, they did not reach a significant level (P>0.05). In the experimental group, the improvement in all the clinical measures of the BASMI index (P<0.01) and in the BASFI index (P=0.003) was statistically significant. The intergroup comparison between the improvement (prepost scores) in both groups showed that the experimental group obtained a greater improvement than the control group in all the clinical measures of the BASMI index, except in tragus to wall distance, as well as in the BASFI index.\n The experimental protocol developed by our research group, based on the GPR method and specific strengthening and flexibility exercises of the muscle chains, offers promising results in the management of patients suffering from AS. Further trials on this topic are required.", "To compare, in patients with ankylosing spondylitis (AS), the effectiveness on pain, functional and psychological status of an intensive group exercise programme under the supervision of a physiotherapist and a home physiotherapy programme.\n Fifty-one patients with AS were randomly allocated into study and control groups. The study was designed as a prospective, double-blind study.\n Outpatient department, Istanbul Medical Faculty.\n Patients who consulted with complaints of pain, morning stiffness and restricted range of movement with a confirmed diagnosis of ankylosing spondylitis.\n Before exercise, both groups were given an education programme about AS. For group I patients an intensive exercise programme was organized under the supervision of a physiotherapist for six weeks. Group II patients had to practise exercises individually at home.\n Both groups were evaluated and compared for pain, functional and psychological status before treatment, at the end of treatment and three months after treatment using a visual analogue scale (VAS) for pain, Beck Depression Scale and Bath Ankylosing Spondylitis Functional Index (BASFI).\n Six patients withdrew, four from group I. Results from the remaining 45 showed more positive changes in the patients undertaking group exercise at six weeks and three months after treatment. Values showed a statistical significant difference in favour of group I.\n Group exercise in hospital may be more effective than home-based exercises at reducing impairment associated with ankylosing spondylitis.", "Home based self-care is essential for successful management of ankylosing spondylitis (AS). We designed an intervention package aimed at promoting self-care and regular longterm exercise and evaluated its effect on outcome.\n Members of our database (n = 4569) were randomly selected and randomized to an intervention group (IG) or a followup control group (CG). The intervention consisted of an exercise/information video, exercise progress chart, patient education booklet, and AS exercise reminder stickers. The outcome measures were function (BASFI), disease activity (BASDAI), global well being (BAS-G), exercise self-efficacy (ESE), arthritis self-efficacy (SES), and quantity of AS mobility/aerobic exercise assessed at baseline and 6 months.\n Of the 200 subjects, 155 completed the study (75 IG and 80 CG). Baseline analysis showed no differences between the CG and the IG. At 6 months, analysis revealed no statistically significant between-group differences for the BASFI, BASDAI, and BAS-G. although the p value of 0.08 for function approached significance. Self-efficacy for exercise showed a significant improvement in the IG (p = 0.045). There were no between-group differences for the SES pain and other symptoms subscales. Finally, there was a significant increase in self-reported AS mobility (p < 0.001) and aerobic exercise (p < 0.05) in the IG.\n An exercise intervention package designed to promote self-management in AS (1) significantly improves self-efficacy for exercise; (2) significantly improves self-reported levels of exercise; (3) reveals a trend for improvement in function (BASFI).", "Fifty-three patients with ankylosing spondylitis (AS) were randomly allocated; 26 experimental patients received physiotherapy and disease education, 27 control patients received neither. The primary treatment outcome was change in spinal mobility measured at 4 months by fingertip-to-floor distance. Experimental patients had more improvement in fingertip-to-floor distance (p2 less than 0.004) and in function (p2 less than 0.001) than control patients. Physiotherapy with disease education is effective in the treatment of patients with AS.", "We investigated the effects of home-based daily exercise on joint mobility, functional capacity, pain, and depression in patients with ankylosing spondylitis (AS). The patients were randomly assigned to a wait-list control group or to an exercise-therapy group. The exercise-therapy group performed a 20-min exercise program once per day for 8 consecutive weeks. After 8 weeks, compared with the control group, the exercise group showed improvements in joint mobility (cervical flexion, extension, shoulder flexion, abduction, hip abduction, and knee flexion), finger-floor distance, and functional capacity. Pain and depression scores were significantly lower after the exercise program in the exercise group than in the control group. These findings indicate that exercise therapy increases joint mobility and functional capacity, and decreases pain and depression in patients with AS. Home-based exercise, which is easily accessible to patients, might be an effective intervention for AS.", "To determine the efficacy of combined spa-exercise therapy in addition to standard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis (AS).\n A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 (mean age 48 +/- 10 years; male:female ratio 25:15) was treated in a spa resort in Bad Hofgastein, Austria; group 2 (mean age 49 +/- 9 years; male:female ratio 28:12) in a spa resort in Arcen, The Netherlands. The control group (mean age 48 +/- 10 years; male:female ratio 34:6) stayed at home and continued their usual drug treatment and weekly group physical therapy during the intervention weeks. Standardized spa-exercise therapy of 3 weeks duration consisted of group physical exercises, walking, correction therapy (lying supine on a bed), hydrotherapy, sports, and visits to either the Gasteiner Heilstollen (Austria) or sauna (Netherlands). After spa-exercise therapy all patients followed weekly group physical therapy for another 37 weeks. Primary outcomes were functional ability, patient's global well-being, pain, and duration of morning stiffness, aggregated in a pooled index of change (PIC).\n Analysis of variance showed a statistically significant time-effect (P < 0.001) and time-by-treatment interaction (P = 0.004), indicating that the 3 groups differed over time with respect to the course of the PIC. Four weeks after start of spa-exercise therapy, the mean difference in PIC between group 1 and controls was 0.49 (95% confidence interval [CI] 0.16-0.82, P = 0.004) and between group 2 and controls was 0.46 (95% CI 0.15-0.78, P = 0.005). At 16 weeks, the difference between group 1 and controls was 0.63 (95% CI 0.23-1.02, P = 0.002) and between group 2 and controls was 0.34 (95% CI--0.05-0.73; P = 0.086). At 28 and 40 weeks, more improvement was found for group 1 compared with controls (P = 0.012 and P = 0.062, respectively) but not for group 2 compared with controls.\n In patients with AS, a 3-week course of combined spa-exercise therapy, in addition to drug treatment and weekly group physical therapy alone, provides beneficial effects. These beneficial effects may last for at least 40 weeks." ]

[ "11516109", "11675332" ]

[ "Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis.", "Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease." ]

[ "A randomized phase II multicenter clinical trial comparing the efficacy of fludarabine (FAMP) to that of the association of cyclophosphamide, doxorubicin and prednisone (CAP) in 92 patients with Waldenstrom's macroglobulinemia in first relapse or with primarily resistant disease, was conducted on the behalf of the 'Groupe Coopératif Macroglobulinémie'. The main analysis of this study failed to demonstrate a clear cut benefit of FAMP in terms of overall survival (OS), although a significant benefit in terms of time to disease progression and event-free survival (EFS) was noted. In this rare disorder, where few randomized trials have been conducted, we took advantage of this trial to assess treatment differences while integrating quality of life considerations. We thus performed a quality-adjusted survival analysis, using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Four health states differing in terms of quality of life (QoL) were defined, namely treatment-related toxicity, treatment free of toxicity, no treatment or symptoms, and relapse. The average time spent in these health states (TOX, CT, TWiST and REL, respectively) were then weighted by utility coefficients reflecting relative QoL value according to that of TWiST and summed up giving the so-called Q-TWiST. No difference was found between randomized groups in terms of mean CT. Mean TOX in the two groups were similarly close except when considering alopecia as a relevant toxic event. By contrast, mean TWiST was 5.9 months longer in the FAMP group than in the CAP group (P = 0.006). Unsurprisingly, given the absence of difference in OS but the difference in EFS in favor of the FAMP group, mean REL was increased by 6.8 months in the CAP group (P = 0.047). As a result, benefit of FAMP in terms of average Q-TWiST only relied on the value of the utility coefficient attributed to REL (U(REL)), with a significant benefit when UREL ranged from 0 to 0.28, ie in patients undergoing poor QoL after relapse, which is likely.", "Few reports are available on the treatment of patients with Waldenström macroglobulinemia (WM) and primary or secondary resistance to alkylating-agent-based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after alkylating-agent therapy were randomly assigned to receive fludarabine (25 mg/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m(2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first end point evaluated was the response rate after 6 treatment courses. Forty-five patients received CAP and 45 received fludarabine. Two patients died before the first course of chemotherapy. No statistical differences were observed between the 2 treatment arms with respect to hematologic toxicity or infections. Mucositis and alopecia occurred significantly more often in patients treated with CAP. Partial responses were obtained in 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P =.019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly higher in this group (P <.01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the median overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents." ]

[ "782141", "7010873" ]

[ "Controlled trial of intravenous aminophylline in acute cerebral infarction.", "Lack of effect of theophylline on the outcome of acute cerebral infarction." ]

[ "In a double-blind trial intravenous aminophylline was compared with placebo in 79 patients with acute cerebral infarction. Immediate improvement in the neurological evaluation score was significantly more frequent in patients receiving aminophylline (38 per cent) than in those on placebo (15 per cent); only patients with mild or moderately severe strokes responded to the injection. After 3 weeks, however, the treated patients did not fare significantly better than the controls in terms of neurological score and residual disability. Survival rate, length of stay in hospital, and social readaptation were similar in the two groups. It is concluded that intravenous aminophylline in patients with ischaemic strokes can bring about an immediate symptomatic relief, but without appreciably influencing the ultimate recovery.", "In patients with acute ischemic stroke, dramatic but often transient improvements have been noticed after theophylline injections. Whether better results could be obtained by continuous infusion of the drug was evaluated in a double-blind study. Out of 46 patients with a mean age of 75 years, 22 got theophylline as aminophylline (bolus dose of 230 mg followed by 0.5 mg/kg/h) and 24 placebo during 3 days. The groups were comparable in all aspects at the outset of the trial. Serum theophylline concentrations were kept within the therapeutic range recommended for patients with asthma. No significant difference in outcome was noticed between the groups during the hospital period when repeated neurological assessments by two different scores and mortality were compared." ]

[ "16798652", "16352815", "12064916", "1978115", "12670352", "8299320" ]

[ "A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassemia major patients from Hong Kong.", "Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis.", "Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial.", "Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients.", "Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients.", "Urinary iron excretion depends on the mode of administration of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with homozygous beta-thalassemia." ]

[ "A controlled, open-label and randomized study was conducted to evaluate the safety and efficacy of the oral iron chelator deferiprone (L1) in thalassemia major patients from Hong Kong. Forty-nine patients were recruited in total (median age: 20 years; range: 8 to 40 years). The division of the patients was determined based on liver iron content and put into either the poorly-chelated (Group I) or well-chelated (Group II) groups. In Group I, 20 patients received combined therapy of L1 daily plus desferrioxamine (DFO), in a reduced frequency of twice weekly, while the control group consisted of 16 patients who were treated with DFO alone. In Group II, six patients received L1 only, while the control group consisted of seven patients treated with DFO alone. Only patients who participated for longer than 6 months were analyzed for efficacy (n = 44). The median study period was 18 months. Transient and mild gastrointestinal upset (31%), joint pain (15%) and liver enzyme elevation (23%) were the most common side effects noted for L1. No case of neutropenia was observed in this study. Serum ferritin (SF) levels showed significant decline in the poorly-chelated patients using combined therapy (L1 and reduced frequency DFO) as compared to those on DFO alone. However, their pre- and post-study liver iron content was not significantly different. Evaluation of the well-chelated group demonstrated no significant change in SF or liver iron content in both the study and control arms. We conclude that the short-term use of L1, with or without DFO, was safe and efficacious in our Chinese patient cohort. The long-term efficacy of reducing iron overload by treatment regimens including L1 requires further study.", "Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial siderosis (myocardial T2(*)) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% +/- 5.3% and 93% +/- 9.7% (P = .81), respectively. The improvement in myocardial T2(*) was significantly greater for deferiprone than deferoxamine (27% vs 13%; P = .023). Left ventricular ejection fraction increased significantly more in the deferiprone-treated group (3.1% vs 0.3% absolute units; P = .003). The changes in liver iron level (-0.93 mg/g dry weight vs -1.54 mg/g dry weight; P = .40) and serum ferritin level (-181 microg/L vs -466 microg/L; P = .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major.", "Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willing to undergo liver biopsy before and after treatment. The mean serum ferritin reduction was 222 +/- 783 ng/ml in the deferiprone and 232 +/- 619 ng/ml in the deferoxamine group (P = 0.81). No difference in the reduction of liver and heart iron content was found by magnetic resonance between the two groups. Thirty-six patients accepted to undergo repeat liver biopsy: 21 in the deferiprone and 15 in the deferoxamine group. Their mean reduction of liver iron content was 1022 +/- 3511 microg/g of dry liver and 350 +/- 524, respectively (P = 0.4). No difference in variation of the Ishak fibrosis stage was observed between the two groups. Treatment was discontinued because of reversible side effects in 5 patients in the deferiprone group (3 hypertransamin/asemia and 2 leukocytopenia) and in none in the deferoxamine group. These findings suggest that deferiprone may be as effective as deferoxamine in the treatment of thalassemia major with few mild and reversible side effects.", "The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) was compared with that of subcutaneous desferrioxamine in 26 patients with transfusional iron overload. Immediately after red-cell transfusion, 20 patients were randomised to receive either desferrioxamine (50 mg/kg daily as a 12 h subcutaneous infusion), or L1 (50 mg/kg daily by mouth). Patients were evaluated during treatment with the other drug after transfusion the next month. Mean (SD) daily urinary iron excretion was lower during L1 than during desferrioxamine (12.3 [6.7] vs 18.2 [15.3] mg/day). In 5 patients the dose of L1 was raised from 50 to 75 mg/kg daily; mean urinary iron excretion rose from 13.8 (7.0) mg/day to 26.7 (17.8) mg/day, comparable with that during desferrioxamine (24.9 [24.3] mg/day). Faecal iron excretion rose slightly over baseline in 6 patients studied during L1 administration (from 8.5 [0.9] mg/day to 12.2 [0.9] mg/day). Pharmacokinetic studies showed an elimination half-life for L1 of 117-237 min. Studies in dogs and in volunteers showed no absorption of the L1-iron complex, excluding a contribution of absorption of intraluminal complexes of L1 and food iron to urinary iron excretion. Further animal toxicity testing is needed before L1 can be studied in a broader group of patients.", "Desferrioxamine (DFX) alone (40-50 mg/kg/d s.c. over 8-12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 +/- 635 microg/l (mean +/- SEM) to 3998 +/- 604 microg/l (P < 0.001; n = 14) in the DFX group and from 4153 +/- 517 microg/l to 2805 +/- 327 microg/l in the combined group (P < 0.01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1.01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side-effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.", "To examine the effect of frequency of oral administration of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion.\n Sustained serum concentrations of L1 will cause more iron chelation than the same daily dose given in larger but less frequent amounts.\n Ten patients with thalassemia with a mean age of 20.9 +/- 4.7 years (range, 13 to 27 years), who were receiving regular treatment with 75 to 100 mg/kg/day oral L1, received 75 mg/kg/day L1 orally in equally divided doses: every 6 hours for 3 days and every 12 hours for 3 days. The two study periods occurred 1 month apart immediately after the monthly blood transfusions. Urine was collected for two consecutive 24-hour periods during each of the different schedules. Serial blood samples were collected from six patients over a 6-hour period and analyzed for total L1 and the L1 glucuronide metabolite concentrations.\n The patient's mean hemoglobin levels (138.8 +/- 12.5 and 139.0 +/- 11.6 gm/L) and ferritin levels (2856.4 +/- 2207.8 and 2890.0 +/- 2264.4 micrograms/L) were similar during the every-6-hour and every-12-hour L1 administrations, respectively. There was significantly more urinary iron excretion when L1 was administered every 6 hours (0.59 +/- 0.29 mg/kg/day) versus every 12 hours (0.40 +/- 0.26 mg/kg/day; p = 0.0129). Calculated 24-hour area under the plasma concentration-time curve of L1 was similar during the every-6-hour (7023.9 +/- 2637.8 mg.min/L) and every-12-hour (7050.1 +/- 1668.8 mg.min/L) experiments.\n These data suggest that the sustained presence of L1 in the blood results in greater chelation of iron than that observed with larger, less frequent doses." ]

[ "372448", "12708131", "7480981", "9116877", "12645832", "12588635", "12639402", "381193", "5047617", "16308544", "15154607", "12117049", "9014601", "3432562", "15641632", "9810030", "15693916", "2717651", "14720270", "4885561" ]

[ "Tylophora indica in bronchial asthma (a controlled comparison with a standard anti-asthmatic drug).", "An experimental and clinical evaluation of anti-asthmatic potentialities of Devadaru compound (DC).", "Effect of menthol vapour on airway hyperresponsiveness in patients with mild asthma.", "Evaluation of efficacy of traditional Chinese medicines in the treatment of childhood bronchial asthma: clinical trial, immunological tests and animal study. Taiwan Asthma Study Group.", "Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: a double-blind placebo-controlled trial.", "A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patients.", "Pycnogenol((R)) in the Management of Asthma.", "Tylophora indica in bronchial asthma--a double blind study.", "Treatment of asthma with an alcoholic extract of tylophora indica: a cross-over, double-blind study.", "Plant-based formulation for bronchial asthma: a controlled clinical trial to compare its efficacy with oral salbutamol and theophylline.", "Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from asthma patients on dietary supplementation with gammalinolenic acid-containing borage oil: possible implication in asthma.", "Treatment of asthma patients with herbal medicine TJ-96: a randomized controlled trial.", "Epogam evening primrose oil treatment in atopic dermatitis and asthma.", "Effect of BN 52063, a specific PAF-acether antagonist, on bronchial provocation test to allergens in asthmatic patients. A preliminary study.", "Pycnogenol as an adjunct in the management of childhood asthma.", "Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study.", "Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma.", "A study of evening primrose seed oil in atopic asthma.", "Butterbur, a herbal remedy, confers complementary anti-inflammatory activity in asthmatic patients receiving inhaled corticosteroids.", "A crossover double-blind study on Tylophora indica in the treatment of asthma and allergic rhinitis." ]

[ "nan", "Devadaru compound was shown to be beneficial in Tamak Swasa (bronchial asthma). Clinical findings revealed higher percentage of relief in cardinal and general symptoms with decrement in the pulse rate and in the respiration rate. A significant linear increase in PEFR value was observed before and after treatment and an increase in FEV1 values measured in Group I subjects. There was relief of all symptoms in a significant number of patients. Occurrence of relief was observed only among patients who suffer less than 10 years duration with Tamak Swasa and among those the frequency of attacks of Tamak Swasa was at fortnightly or monthly intervals. Antispasmodic activity of Devadaru Compound (DC) on acetylcholine (Ach) induced contractions using rat ileum preparation was studied. The results demonstrated that DC inhibits Ach-induced contractions significantly and bears a dose-response relationship. This suggests that DC has got anti-spasmodic activity and corroborates the clinical findings. The clinical findings and experimental studies show that DC is of significant use in the treatment of Tamak Swasa (Bronchial Asthma) and superior to the standard and placebo therapy.", "nan", "Traditional Chinese medicines (TCM) have been used to treat bronchial asthma for several centuries and a certain degree of clinical benefit has been observed; however, scientific substantiation is lacking. A multicenter, double-blind and placebo-controlled study was therefore conducted to evaluate the clinical efficacy in terms of symptom score, medication score, morning and evening PEFRs, and changes of immunoregulatory function, such as distribution of lymphocyte subsets and in vivo and in vitro production of lymphokines (IFN-gamma and IL-4) and inflammatory mediators (histamine, PGE2 and LTC4). Furthermore, the protective effect of TCM on the late asthmatic reaction (LAR) was evaluated by using asthmatic guinea pigs. Three hundred and three asthmatic children were classified by Chinese doctors, according to a standardized questionnaire designed on the basis of basic logic of Chinese medicine, into three groups of specific constitution (group A, B and C). Group A consisted of 32 herb A-treated patients and 34 placebo-treated; group B, 74 herb B-treated and 64 placebo-treated; and group C, 55 herb C-treated and 44 placebo-treated. The study period was six months. The results were: 1) Both treatment group and placebo group showed an improvement in all clinical parameters, thus demonstrating a placebo effect. However, the improvement was usually greater in the former than the latter, although only the difference in PEFR was significant; 2) Herb A could increase total T cell and decrease B cell; 3) Herb A and B enhanced production of PGE2 but not LTC4, IFN-gamma and IL-4; 4) There was a general tendency for in vivo and in vitro production of histamine to decrease at the end of study in both treatment group and placebo group; however, the decrease was significantly greater in the former than the latter; 5) In asthmatic guinea pigs, 10-day's pretreatment with Chinese herbs could reverse the decrease of sGaw, suppress eosinophilia in bronchoalveolar lavage fluid (BALF), prevent the eosinophil infiltration of airways, increase PGE2 production and decrease LTC4 production in serum and BALF. Thus, traditional Chinese medicines did show a certain degree of clinical efficacy. The decreased production of histamine and LTC4, increased production of PGE2 that were found in both asthmatic children and asthmatic guinea pigs, and prevention of occurrence of LAR by suppressing eosinophil infiltration of airways and preserving airway conductance that were observed in asthmatic guinea pigs after allergen challenge might be used to account partly for the effectiveness.", "Airway hypersecretion is mediated by increased release of inflammatory mediators and can be improved by inhibition of mediator production. We have recently reported that 1.8-cineol (eucalyptol) which is known as the major monoterpene of eucalyptus oil suppressed arachidonic acid metabolism and cytokine production in human monocytes. Therefore, the aim of this study was to evaluate the anti-inflammatory efficacy of 1.8-cineol by determining its prednisolone equivalent potency in patients with severe asthma. Thirty-two patients with steroid-dependent bronchial asthma were enrolled in a double-blind, placebo-controlled trial. After determining the effective oral steroid dosage during a 2 month run-in phase, subjects were randomly allocated to receive either 200 mg 1.8-cineol t. i.d. or placebo in small gut soluble capsules for 12 weeks. Oral glucocorticosteroids were reduced by 2.5 mg increments every 3 weeks. The primary end point of this investigation was to establish the oral glucocorticosteroid-sparing capacity of 1.8-cineol in severe asthma. Reductions in daily prednisolone dosage of 36% with active treatment (range 2.5-10 mg, mean: 3.75 mg) vs. a decrease of only 7% (2.5-5 mg, mean: 0.91 mg) in the placebo group (P = 0.006) were tolerated. Twelve of 16 cineol vs. four out of 16 placebo patients achieved a reduction of oral steroids (P = 0.012). Long-term systemic therapy with 1.8-cineol has asignificant steroid-saving effect in steroid-depending asthma. This is the first evidence suggesting an anti-inflammatory activity of the monoterpene 1.8-cineol in asthma and a new rational for its use as mucolytic agent in upper and lower airway diseases.", "The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of > 15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2-5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19-52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19% increase in FVC, a 29.5% increase in FEV1, a 30% increase in peak expiratory flow rate (PEFR), and a 41% increase in the forced expiratory flow rate between 25 and 75% of the vital capacity (FEF25-75). The clinical improvement was associated with decreases by 52, 65, 44 and 30%, respectively, of initial values for the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, ICAM-1, interleukin (IL)-6 and IL-8, and a 3-fold increase in the 'protective' cytokine IL-10. The levels of prostaglandins E2 and F2alpha and leukotriene D4 were decreased significantly to 36, 39, and 28%, respectively, of initial values. Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators. The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients. The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents.", "Asthma is characterized as a chronic inflammatory process. Pycnogenol((R)), a bioflavonoid mixture extracted from Pinus maritima, is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties. The objective of this study was to evaluate the efficiency of this agent in a randomized, double-blinded, placebo-controlled, crossover study in patients with varying asthma severity. Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study. Medical history, physical examination, blood sample analyses, and spirometric values were obtained at baseline, 4 weeks, and 8 weeks. The patients were randomly assigned to receive either 1 mg/lb/day (maximum 200 mg/day) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks. No adverse effects were observed related to the study drug. Within the contingent of 22 patients who completed the study, almost all responded favorably to Pycnogenol in contrast to placebo. Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo. The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma. We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy.", "nan", "nan", "Plant-based medicine is the 3rd most popular choice of both adults (11%) and children (6%) suffering from Asthma. While several plant-based formulations have been reported for the treatment of asthma in the past, many authors have published their reservations on clinical trials carried out using complementary and alternative medicines.\n The authors desired to eliminate the shortcomings of the earlier clinical trials carried out by many investigators in a structured study. Therefore, a 12-week randomized double-blind placebo-controlled clinical study was conducted to investigate the efficacy of a plant-based formulation (DCBT4567-Astha-15) in comparison with oral salbutamol, salbutamol + theophylline and a matching placebo in patients with reversible asthma.\n Ninety-four patients between 15 and 50 years of age, showing 15% improvement in forced expiratory volume in 1 s (FEV(1)) 15 min after a bronchial challenge of inhaled salbutamol (200 microg) were recruited, and the end point of the study was determined as a 15% improvement in FEV(1) and clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, sleep disturbances and respiration rate.\n DCBT4567-Astha-15, salbutamol and salbutamol + theophylline patients showed statistically significant improvement in FEV(1), while placebo patients did not show any improvement. Fifty percent of DCBT4567-Astha-15, 48% of salbutamol, 58% of salbutamol + theophylline and 26% of placebo patients showed the desired 15% improvement in FEV(1). Improved mean FEV(1) values at the end of the trial indicated that the salbutamol - theophylline combination was superior followed by salbutamol and DCBT4567-Astha-15. Clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, and sleep disturbances were significantly reduced in DCBT4567-Astha-15 patients compared to patients of the other three arms.\n DCBT4567-Astha-15 was as efficacious as salbutamol (12 mg/day) or salbutamol (12 mg/day) in combination with theophylline (200 mg/day) in the treatment of reversible asthmatics. Quality of life of patients also improved with DCBT4567-Astha-15 drug treatment.", "Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX) and suppressor of leukotriene B4 (LTB4), can attenuate the clinical course of rheumatoid arthritics, with negligible side effects. Since Zileuton, also an inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we investigated whether dietary GLA would suppress biosynthesis of PMN-LTB4 isolated from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma patients (16-75 years) were randomized to receive either 2.0 g daily GLA (borage oil) or corn oil (placebo) for 12 months. Blood drawn at 3 months intervals was used to prepare sera for fatty acid analysis, PMNs for determining phospholipid fatty acids and for LTB4 generation. Patients were monitored by daily asthma scores, pulmonary function, and exhaled NO. Ingestion of daily GLA (i) increased DGLA (GLA metabolite) in PMN-phospholipids; (ii) increased generation of PMN-15-HETrE (5-LOX metabolite of DGLA). Increased PMN-DGLA/15-HETrE paralleled the decreased PMN generation of proinflammatory LTB4. However, the suppression of PMN-LTB4 did not reveal statistically significant suppression of the asthma scores evaluated. Nonetheless, the study demonstrated dietary fatty acid modulation of endogenous inflammatory mediators without side effects and thus warrant further explorations into the roles of GLA at higher doses, leukotrienes and asthma.", "Alternative medicine use has increased at a remarkable pace all over the world in recent years. Although herbal medicine for the treatment of asthma is becoming the focus of public attention, randomized studies had not been performed, even in Eastern countries including Japan. This study was designed to investigate whether one of the Japanese government approved herbal complexes Saiboku-to (TJ-96) is effective for the treatment of atopic asthma, and to investigate whether this protective activity is associated with a reduction in eosinophilic inflammation. A double-blind, randomized, crossover design was used. Subjects received 2.5 g of TJ-96 or placebo orally 3 times daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with TJ-96 on bronchoconstriction precipitated by inhalation of methacholine. Furthermore, eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed. After 4 weeks of treatment with TJ-96, values of PC20 -methacholine significantly improved in the treatment with TJ-96. Also, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Our results suggest that TJ-96 has an antiinflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of asthma.", "Essential fatty acids are claimed to have positive effects in atopic diseases. In a double blind, placebo controlled, parallel group study 58 out of 60 children, with atopic dermatitis and the need for regular treatment with topical skin steroids, completed a 16 weeks' treatment period with either Epogam evening primrose oil or placebo capsules. Twenty two of these subjects also had asthma. The parents used diaries to record symptom scores and concomitant medication. Peak expiratory flow was measured and disease activity was monitored by the clinician every four weeks. The plasma concentrations of essential fatty acids increased significantly in the group treated with Epogam capsules. The study demonstrated significant improvements of the eczema symptoms but no significant difference was found between the placebo and the Epogam groups. No therapeutic effect was shown on asthma symptoms or fidget.", "Platelet Activating Factor, PAF-acether, elicits acute and more prolonged inflammatory responses in both experimental animals and man, and is recognised as a possible mediator of asthma. The effect of a specific PAF-acether antagonist, BN 52063, on the early asthmatic response to inhaled allergen was assessed in a randomised, double-blind, crossover study in eight atopic asthmatics, who received three days treatment with BN 52063 or placebo, separated by a one week washout. On the third day of treatment, subjects were challenged with nebulised house dust mite or pollen allergen. BN 52063 significantly antagonised early bronchoconstriction and showed a tendency to inhibit residual bronchial hyperreactivity, assessed six hours after allergen challenge by a provocation test to acetylcholine. No side effects were reported during active treatment. This is the first study in man demonstrating the efficacy of a specific PAF-acether antagonist on the immediate response to inhaled allergen challenge in asthmatics. The findings support the possible role of specific PAF-acether antagonists in the treatment of asthma.", "A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol or placebo. Subjects were instructed to record their peak expiratory flow with an Assess Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C4/D4/E4 was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol group. The results of this study demonstrate the efficacy of Pycnogenol as an adjunct in the management of mild-to-moderate childhood asthma.", "The gum resin of Boswellia serrata, known in Indian Ayurvedic system of medicine as Salai guggal, contains boswellic acids, which have been shown to inhibit leukotriene biosynthesis. In a double-blind, placebo-controlled study forty patients, 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness, bronchial asthma, of 9.58 +/- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks. 70% of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea, rhonchi, number of attacks, increase in FEV subset1, FVC and PEFR as well as decrease in eosinophilic count and ESR. In the control group of 40 patients 16 males and 24 females in the age range of 14-58 years with mean of 32.95 +/- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks. Only 27% of patients in the control group showed improvement. The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma.", "The aim of this study was to evaluate the efficacy and safety of a Chinese herbal formula modified Mai-Men-Dong-Tang (mMMDT) for treatment of persistent, mild-to-moderate asthma. A total of 100 asthmatic patients were enrolled and assigned to three treatment groups in this double-blind, randomized, placebo-controlled clinical trial. Over a period of 4 months, patients in groups A and B received 80 and 40 mg/kg/day of mMMDT, while those in group C received a placebo. Efficacy variables included changes in forced expiratory volume in 1 s (FEV1), symptom score, serum total immunoglobulin E (IgE), and dust mite-specific IgE. Safety assessments included complete blood count, and liver and kidney function. Relative to baseline, significantly greater increases in FEV1 were demonstrated for both A and B groups in comparison with the placebo-treated analog (both p <0.05). Further, similar improvements in symptom score were observed for both mMMDT treatment groups. The serum total IgE for group A showed a decreasing tendency after treatment but no statistical difference was noted. Furthermore, no drug-related adverse effects were reported. Blood test, and liver and kidney function were within normal range during the study, with no marked changes demonstrated over time. In conclusion, the Chinese herbal formula mMMDT provided improvements in lung function and relieved asthma symptoms in our sample of patients. Given its efficacy and safety, we consider mMMDT a credible treatment regimen for persistent, mild-to-moderate asthma.", "It has shown recently that Evening Primrose Oil (Efamol) produces a significant clinical improvement in atopic eczema. Efamol contains gamma-linolenic acid which is a precursor to PGE1 a more consistent bronchodilator than PGE2. We have conducted a double blind placebo controlled study in atopic asthmatics given Efamol for an eight week period looking at the control of asthma, including histamine challenge tests. We have found no effect on the asthma or challenge tests although Efamol produced an alteration in fatty acid profile. The patients showed an abnormal fatty acid profile. We speculate that such fatty acid abnormalities could be important in the aetiology of asthma.", "The effects of butterbur (BB), a herbal remedy, as add-on therapy to inhaled corticosteroids in patients with atopic asthma is currently unknown.\n We evaluated the effects of BB, given as add-on therapy to asthmatic patients maintained on inhaled corticosteroids, assessing adenosine monophosphate (AMP) bronchoprovocation (primary outcome variable) along with other surrogate inflammatory markers such as exhaled nitric oxide, serum eosinophil cationic protein and peripheral blood eosinophil count.\n Sixteen atopic asthmatic patients with mean (standard error of mean) forced expiratory volume in 1 s (FEV1) of 78 (4)% predicted, maintained on their constant dose of inhaled corticosteroids throughout the study, received twice daily for 1 week either BB 25 mg or placebo (PL), in a double-blind, cross-over fashion, with a 1-week washout period prior to each randomized treatment. Measurements were made at baselines prior to each randomized treatment and following the randomized treatment period.\n Baseline values for the primary and secondary outcomes were not significantly different prior to BB and PL. AMP provocative concentration causing a 20% reduction from baseline FEV1 (PC20) as doubling dilution change from baseline, significantly improved (P<0.05) with BB, 0.6 (0.2), compared with PL, -0.1 (0.3); a 0.7 doubling dilution difference. Exhaled nitric oxide as change from baseline was significantly reduced (P<0.05) with BB, -1.2 (0.8) p.p.b., compared with PL, 0.5 (0.4) p.p.b. Both serum eosinophil cationic protein and peripheral blood eosinophil count as change from baseline were also significantly suppressed (P<0.05) with BB, -3.9 (3.3) microg/L, -31 (28)x106/L compared with PL, 3.3 (2.5) microg/L, 38 (16)x106/L, respectively.\n Chronic dosing with BB conferred complementary anti-inflammatory activity in atopic asthmatic patients maintained on inhaled corticosteroids. Further studies are now required to assess the potential role for BB as either monotherapy in milder patients or add-on therapy in more severe asthmatics.", "nan" ]

[ "7962426", "8329110", "9436670", "2029326", "14996420", "2859409", "8607936", "11870141", "10221723", "10437864", "8567794", "9506206", "2029327" ]

[ "Immunotherapy and recurrent abortion: a randomized clinical trial.", "Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial.", "Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study.", "Immunotherapy for recurrent spontaneous abortions in a Chinese population.", "Induction of MLR-Bf and protection of fetal loss: a current double blind randomized trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion.", "Controlled trial of treatment of recurrent spontaneous abortion by immunisation with paternal cells.", "Intravenous immunoglobulin for treatment of recurrent pregnancy loss.", "A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage.", "Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study.", "Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial.", "Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i.v. immunoglobulin.", "Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin: a prospective, randomized, double-blinded, placebo-controlled trial.", "Treatment of recurrent aborters by immunization with paternal cells--controlled trial." ]

[ "We conducted a randomized trial comparing expectant management versus immunotherapy with paternal leukocytes to improve obstetric outcome in women with unexplained recurrent abortion. Eligible for the study were women with unexplained recurrent abortion (three or more miscarriages and no live birth), negative findings of immunological screening and no inhibition of the mixed lymphocyte culture. These women were seen for the first time between October 1988 and March 1991 in a network of obstetric departments in Northern Italy. Subjects positive for HLA DR3 or with a partner positive for hepatitis virus B antigen were not eligible. A total of 44 women entered the study. Patients were randomly allocated to immunotherapy (22 women) or expectant management (22 women). Women allocated to immunotherapy were given 200 x 10(6) purified paternal lymphocytes before pregnancy. Median follow-up was 24 months (range 10-39) in the immunotherapy group and 25 months (range 11-38) in the expectant management group. Out of the 22 women randomized to immunotherapy, 16 became pregnant and the corresponding value was 14 in the expectant management group. Spontaneous abortion occurred in six out of the 16 pregnancies observed in the treated women. Among the 14 pregnancies observed in the expectant management group, two aborted and one late fetal death occurred. The cumulative proportions of women who became pregnant over 4 years were 37 and 45% in the immunotherapy and expectant management groups respectively; this difference was not significant. No adverse effect was observed in treated women.", "It remains unclear whether maternal immunization with paternal lymphocytes prior to conception improves the reproductive outcome in women with recurrent abortion in whom all secondary causes have been excluded.\n A double-blind placebo controlled trial was instituted in women with unexplained recurrent spontaneous abortion, comparing immunization with 400 million paternal to 400 million maternal (autologous) lymphocytes. The groups were compared in a paired sequential trials chart, by logistic regression, and, in addition, a meta-analysis of this and other published trials was carried out.\n The live birth rate among pregnancies in paired couples with paternal lymphocyte immunization was 68% compared to 47% in the women who received their own cells. The results bordered on, but did not achieve, statistical significance. The women in each group were thoroughly investigated to exclude known causes of recurrent pregnancy loss and appeared to have been well matched in all variables. Women with lymphocytotoxic antibodies against paternal lymphocytes were excluded. Unlike our previous study there was not association between the time to conception and the chance of a successful outcome. Indeed, the time to conception was relatively short, 12 wk in all groups. The meta-analysis supported an overall modest favorable experience with paternal cells.\n The study is consistent with a general trend favoring paternal over maternal lymphocyte immunization but reinforces the need for larger multicenter controlled trials as well as more detailed biological study in humans to understand the nature of the maternal-fetal interface and its breakdown.", "It is still unclear whether i.v. immunoglobulins (Ig) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss. We report the results of a multicentre placebo-controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages. All were screened to exclude chromosomal or Müllerian abnormalities, the presence of antinuclear antibodies, lupus anticoagulant (LA) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem. To avoid a selection bias towards ongoing pregnancies, i.v. Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected. A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development. In all, 68% of the women who received Ig went to term versus 79% of those who received a placebo (not significant), with no significant differences in the pregnancy course or the perinatal outcome. These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy.", "The efficacy of immunotherapy for the treatment of recurrent spontaneous abortions was tested in patients selected from the same ethnically homogeneous population of Chinese in Taiwan in whom the immunogenetics of gestational trophoblastic tumors and of recurrent spontaneous abortion had been studied. The patients, who included both primary and secondary aborters, were randomly assigned to three groups: those who were immunized with their own lymphocytes (controls) (49); those who were immunized with their husbands' lymphocytes (39); and those who were immunized with third party lymphocytes (11). The data were analyzed individually for the primary and secondary aborters and collectively for both groups combined. The number of babies born, the number of current pregnancies, and the number of recurrent abortions were not statistically significantly different between the control and the immunized groups, and a similar small number of congenital abnormalities (4-9%) occurred in both the control and immunized groups. The increase in the blocking effect for the mixed lymphocyte reaction was not related to the success of the postimmunization pregnancies. Thus, this study does not show any significant improvement in the rate of livebirths in women immunized with their husbands' lymphocytes or with third party lymphocytes compared to that in a placebo-controlled group of women.", "The present study was conducted to evaluate the efficacy of paternal lymphocyte (PL) immunotherapy and its relation with the development of mixed lymphocyte reaction blocking antibodies (MLR-Bf) and the success of pregnancy outcome in women with recurrent spontaneous abortion (RSA). A total of 124 women with unknown causes of abortions was registered for immunotherapy under double blind randomized trial by using the list of computer-generated numbers. Each 5 x 10(6) autologous lymphocyte (AL), third party lymphocyte (TPL) and PL was dissolved separately in 1 ml of sterile normal saline (NS). Each 1 ml of cell suspension and neat NS was injected in women with RSA through intramuscular (250 microl), intradermal (250 microl), subcutaneous (250 microl) and intravenous (250 microl) routes. All women participants with RSA received six identical immunizations at the regular interval of 4 weeks, and were then screened for the development of MLR-Bf after the completion of immunization course, and also at the first, second and third trimesters (12th, 24th and 36th weeks) of pregnancy. However, nonimmunized MLR-Bf positive women with RSA did not receive any kind of therapy (NT) and were used as one of the control group in the present study. We have observed that PL-immunized women with RSA showed a significantly increased level of MLR-Bf (>30) and pregnancy success (84%) as compared to those women with RSA who received either AL (33%), TPL (31%), NS (25%) or those who did not receive any kind of treatment (NT, 44%; P<0.001). Our results indicated the importance of immunotherapy with PL in women with RSA and also showed that MLR-Bf can be considered as one of the important factors for pregnancy improvement.", "In a paired sequential double-blind trial of immunological treatment of recurrent spontaneous abortion successful outcome of the next pregnancy was significantly more common in women injected with purified lymphocytes prepared from their husbands' blood than in those injected with their own lymphocytes. 17 of 22 women given paternal cells had successful pregnancies, compared with 10 of 27 given their own cells.", "Efficacy of immunotherapy for treatment of recurrent spontaneous abortion (SA) has been controversial. The low treatment effect of white blood cell immunization lead to investigations of alternative treatments including intravenous (i.v.) immunoglobulin (Ig). To evaluate the efficacy of IVIg for treatment of recurrent SA, a prospective, randomized, double blinded, placebo-controlled trial was performed.\n Ninety-five women experiencing two or more consecutive spontaneous abortions, with no known cause were randomized and received either IVIg 500 mg/kg/month or placebo (albumin).\n Of 95 women participating in the study, 47 received IVIg and 48 received placebo. Medication was discontinued in 34 women who failed to conceive within four cycles. The remaining 61 women achieved pregnancy. Pregnancy outcomes included 29 deliveries and 32 recurrent SA. Among women delivering live births 18 (62%) received IVIg and 11 (38%) received placebo. By contrast, 21 (66%) women experiencing recurrent SAs received placebo and 11 (34%) received IVIg. Among 61 women who conceived, 29 received IVIg and 32 received placebo. Of the 29 women who conceived and received IVIg, 18 (62%) delivered live births and 11 (38%) experienced recurrent SA. Of 32 women who conceived and received placebo 11 (34%) delivered live births and 21 (66%) had recurrent SA. The difference in live birth rates between women receiving IVIg and placebo was significant (P = 0.04, odds ratio 3.1).\n IVIg is effective in enhancing the percentage of live births among women experiencing unexplained recurrent SA.", "Previous trials of intravenous immunoglobulin (IvIg) treatment of women with recurrent miscarriage (RM) have provided diverging results. This may be due to different inclusion criteria and suboptimal treatment protocols in some trials.\n According to a computer-generated list, 58 women with at least four unexplained miscarriages were randomly assigned to receive infusions of high doses of IvIg or placebo starting as soon as the pregnancy test was positive.\n In the intention-to-treat analysis, a 45% live birth rate was found in both allocation groups. In patients with secondary RM, 50% in the treatment group and 23% in the placebo group had successful pregnancies (P = not significant). When data from the present and a previous placebo-controlled trial of the same treatment were combined, 15/26 (58%) of the patients with secondary RM in the treatment group versus 6/26 (24%) in the placebo group had successful outcomes (P < 0.02). Only 7% of the karyotyped abortuses were abnormal.\n IvIg may improve pregnancy outcome in patients with secondary RM. A new placebo-controlled trial focusing on this subgroup should be conducted to confirm the results.", "The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo.", "Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus. Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses. However, the published results on this treatment are conflicting. In this study (the Recurrent Miscarriage [REMIS] Study), we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies.\n Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind, multicentre, randomised clinical trial. 91 were assigned immunisation with paternal mononuclear cells (treatment) and 92 immunisation with sterile saline (control). The primary outcomes were the inability to achieve pregnancy within 12 months of randomisation, or a pregnancy which terminated before 28 weeks of gestation (failure); and pregnancy of 28 or more weeks of gestation (success). Two analyses were done: one included all women (intention to treat), and the other included only those who became pregnant.\n Two women in each group received no treatment, and eight (three treatment, five control) were censored after an interim analysis. In the analysis of all randomised women who completed the trial, the success rate was 31/86 (36%) in the treatment group and 41/85 (48%) in the control group (odds ratio 0.60 [95% CI 0.33-1.12], p=0.108). In the analysis of pregnant women only, the corresponding success rates were 31/68 (46%) and 41/63 (65%; odds ratio 0.45 [0.22-0.91], p=0.026). The results were unchanged after adjustment for maternal age, number of previous miscarriages, and whether or not the couple had had a previous viable pregnancy. Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth.\n Immunisation with paternal mononuclear cells does not improve pregnancy outcome in women with unexplained recurrent miscarriage. This therapy should not be offered as a treatment for pregnancy loss.", "The aim of this trial was to investigate whether infusions of i.v. immunoglobulins (Ig) to women with secondary recurrent spontaneous abortions and recurrent second trimester spontaneous abortions can increase the rate of successful pregnancy. In a prospective, double-blind, placebo-controlled trial, infusions of i.v. Ig (Nordimmun) or placebo were given during pregnancy to 34 women with a history of either unexplained recurrent spontaneous abortion subsequent to a birth or including at least one second trimester miscarriage. The success rate was 52.9% in the i.v. Ig group compared with 29.4% in the placebo group (not significantly different, therapeutic gain 23.5%, 95% confidence interval -8.6 to 55.7%). No changes in autoantibody concentrations or major lymphocyte subsets were induced by i.v. Ig treatment. In conclusion, an expected 55% therapeutic gain of i.v. Ig in recurrent spontaneous abortion could not be confirmed using the treatment regimen tested. However, to determine whether the trend of therapeutic gain of i.v. Ig in these women may be statistically significant, a larger trial is in progress.", "The efficacy of intravenous immunoglobulin (IVIG) for treatment of unexplained recurrent spontaneous abortion was assessed in a prospective, randomized, double-blinded, and placebo-controlled study.\n The study took place in a provincial recurrent pregnancy loss clinic, located in a tertiary/quaternary care academic center. The study subjects were women with a history of two or more documented consecutive spontaneous pregnancy losses under 20 weeks of gestation, excluding any associated with aneuploidy by karyotype analysis, and with no evidence of genetic, endocrine, infectious, anatomic, or autoimmune factors associated with a history of recurrent spontaneous abortion. The subjects were randomized to receive either intravenous immunoglobulin (Gamimune N) as treatment or normal saline as placebo. Randomization was stratified for primary, secondary, and unclassified unexplained recurrent spontaneous abortion. Success was defined as an ongoing pregnancy beyond 20 weeks of gestation.\n Sixty-two subjects enrolled in the trial. There were 37 index pregnancies and 6 cross-over pregnancies. There was no clinically significant difference between the treatment arm and the placebo arm in terms of subsequent pregnancy success. There seemed to be a higher success rate with the stratified analysis of couples with secondary unexplained recurrent spontaneous abortion, but the trial did not have sufficient power to confirm this.\n Based on this trial and three similar trials in the literature, a multicentered trial is needed to determine conclusively whether IVIG is effective in the treatment of unexplained recurrent spontaneous abortion.", "A paired sequential trial was undertaken to establish whether paternal mononuclear cells improved the prognosis in couples with recurrent abortions. For this purpose, 10(7)-10(8) cells obtained from the blood of partners were injected intravenously, subcutaneously, and intra-dermally into women who had had three or more consecutive miscarriages with the same partner. Control women were given normal saline, injected in the same manner. The result of the sequential analysis showed that there was no significant beneficial effect of the cells compared to control. The overall success rate was 70% (32/46 couples). The success rate in patients given cells was 62% (13/21), while in those given saline it was 76% (19/25). While the overall success rate in this study compares with a number of other studies, we find an equally high success rate with non-immunized patients. We conclude that the value of immunization for the prevention of recurrent miscarriage has not been established." ]

[ "8245085", "12377902", "8821279" ]

[ "Intra-articular fractures of the calcaneum treated operatively or conservatively. A prospective study.", "Operative compared with nonoperative treatment of displaced intra-articular calcaneal fractures: a prospective, randomized, controlled multicenter trial.", "Operative vs. nonoperative treatment of intra-articular fractures of the calcaneus: a prospective randomized trial." ]

[ "We report a prospective trial of 66 patients with intraarticular fractures of the calcaneum. All fractures were assessed by CT. Patients with displaced fractures were randomised to receive either conservative (n = 31) or operative treatment (n = 25). Undisplaced fractures (n = 10) were treated conservatively. Operation involved open reduction of the posterior subtalar joint, and fixation with Kirschner wires. All 66 patients were reviewed at a minimum of one year (mean 23 months). After conservative treatment the undisplaced fractures had slightly better results than the displaced fractures. There was no significant difference in outcome between the operatively and the conservatively treated displaced fractures. We have also documented prospectively the natural history of the injury, which is of use in assessing prognosis for both clinical and medicolegal purposes.", "Open reduction and internal fixation is the treatment of choice for displaced intra-articular calcaneal fractures at many orthopaedic trauma centers. The purpose of this study was to determine whether open reduction and internal fixation of displaced intra-articular calcaneal fractures results in better general and disease-specific health outcomes at two years after the injury compared with those after nonoperative management.\n Patients at four trauma centers were randomized to operative or nonoperative care. A standard protocol, involving a lateral approach and rigid internal fixation, was used for operative care. Nonoperative treatment involved no attempt at closed reduction, and the patients were treated only with ice, elevation, and rest. All fractures were classified, and the quality of the reduction was measured. Validated outcome measures included the Short Form-36 (SF-36, a general health survey) and a visual analog scale (a disease-specific scale).\n Between April 1991 and December 1997, 512 patients with a calcaneal fracture were treated. Of those patients, 424 with 471 displaced intra-articular calcaneal fractures were enrolled in the study. Three hundred and nine patients (73%) were followed and assessed for a minimum of two years and a maximum of eight years of follow-up. The outcomes after nonoperative treatment were not found to be different from those after operative treatment; the score on the SF-36 was 64.7 and 68.7, respectively (p = 0.13), and the score on the visual analog scale was 64.3 and 68.6, respectively (p = 0.12). However, the patients who were not receiving Workers' Compensation and were managed operatively had significantly higher satisfaction scores (p = 0.001). Women who were managed operatively scored significantly higher on the SF-36 than did women who were managed nonoperatively (p = 0.015). Patients who were not receiving Workers' Compensation and were younger (less than twenty-nine years old), had a moderately lower Böhler angle (0 degrees to 14 degrees ), a comminuted fracture, a light workload, or an anatomic reduction or a step-off of < or =2 mm after surgical reduction (p = 0.04) scored significantly higher on the scoring scales after surgery compared with those who were treated nonoperatively.\n Without stratification of the groups, the functional results after nonoperative care of displaced intra-articular calcaneal fractures were equivalent to those after operative care. However, after unmasking the data by removal of the patients who were receiving Workers' Compensation, the outcomes were significantly better in some groups of surgically treated patients.", "Thirty patients with displaced, intra-articular calcaneus fractures were randomized to operative or nonoperative treatment. All patients had two or three major articular fragments of the posterior facet (Sanders type II or III). Nonoperative treatment included early mobilization and delayed weightbearing. Operative treatment involved open reduction and rigid internal fixation with a plate and screws through an extensile, L-shaped lateral approach followed by early mobilization and delayed weightbearing. Fifteen operative patients were evaluated at an average of 17 months follow-up and 11 nonoperative patients were seen at 14 months average follow-up. In the operative group, there were 7 excellent results, 5 good results, 2 fair results, and 1 poor result, and in the nonoperative group there was 1 excellent result, 3 good results, 1 fair result, and 6 poor results (difference significant as P < 0.01). A functional scoring system of 0-100 points was developed based upon the responses to an outcome assessment questionnaire. The average functional score for the operative group was far superior at 86.7, compared with 55.0 for the nonoperative group (P < 0.0001). Subtalar range of motion averaged 20 degrees for the operative group and 17 degrees for the nonoperative group with pain on extremes of motion of 25% of the operative patients compared with 100% of the nonoperative patients. This study is the first prospective, randomized trial to demonstrate the superior results of current operative treatment with early mobilization compared with nonoperative treatment." ]

[ "12603234", "17576774", "7669541", "10982577", "9925042", "10048112", "9256568", "8223364", "17426046", "11456079", "2030194", "11162323", "16499517", "8543703", "15365111", "2071729", "9808825", "18677882", "7287975", "3224003", "3239463", "3529480", "11397745", "9551726", "1571877", "3336245", "2794181", "15013579", "1776536", "1452449", "3592033", "17995993", "15896835", "10181019", "8506786", "16377603", "17523995", "10600434", "2926945", "2319049", "14982550", "7971879", "12780372", "2782119", "11509461", "7852062", "17154745", "9079579", "11072391", "11302275", "1425545", "18236302", "7608359", "15367070", "10688938", "6437257", "3378904", "6666695", "15152882", "6629578", "3369327", "6478779", "6511396", "8442622" ]

[ "A controlled trial of an expert system and self-help manual intervention based on the stages of change versus standard self-help materials in smoking cessation.", "A randomized trial of targeted educational materials for smoking cessation in African Americans using transdermal nicotine.", "Targeting adult smokers through a multi-ethnic public school system.", "Using radon risk to motivate smoking reduction: evaluation of written materials and brief telephone counselling.", "Interactive versus noninteractive interventions and dose-response relationships for stage-matched smoking cessation programs in a managed care setting.", "Targeting smokers with low readiness to change with tailored and nontailored self-help materials.", "Nicotine patch and self-help video for cigarette smoking cessation.", "Standardized, individualized, interactive, and personalized self-help programs for smoking cessation.", "Using radon risk to motivate smoking reduction II: randomized evaluation of brief telephone counseling and a targeted video.", "Evaluating a population-based recruitment approach and a stage-based expert system intervention for smoking cessation.", "Evaluation of intrinsic and extrinsic motivation interventions with a self-help smoking cessation program.", "Counselor and stimulus control enhancements of a stage-matched expert system intervention for smokers in a managed care setting.", "Helping smokers to decide on the use of efficacious smoking cessation methods: a randomized controlled trial of a decision aid.", "A randomized trial of self-help materials, personalized feedback, and telephone counseling with nonvolunteer smokers.", "Post-intervention effect of a computer tailored smoking cessation programme.", "Self-help quit smoking interventions: effects of self-help materials, social support instructions, and telephone counseling.", "A self-help intervention for African American smokers: tailoring cancer information service counseling for a special population.", "The effectiveness of tailored feedback and action plans in an intervention addressing multiple health behaviors.", "Self-help books and amount of therapist contact in smoking cessation programs.", "A randomized comparison of Worksite-sponsored smoking cessation programs.", "Nicotine gum and self-help manuals in smoking cessation: an evaluation in a medical context.", "Effect of a \"stop smoking\" booklet on smokers attending for chest radiography: a controlled study.", "Cost effectiveness of computer tailored and non-tailored smoking cessation letters in general practice: randomised controlled trial.", "Effectiveness of postal smoking cessation advice: a randomized controlled trial in young men with reduced FEV1 and asbestos exposure.", "Evaluation of the \"Time to Quit\" self-help smoking cessation program.", "Effectiveness of smoking cessation interventions integrated into primary care practice.", "Computerized smoking cessation program for the worksite: treatment outcome and feasibility.", "Effectiveness of smoking cessation self-help materials in a lung cancer screening population.", "A comparison of self-help approaches to smoking cessation.", "The impact of tailored self-help smoking cessation guides on young mothers.", "Evaluation of a minimal-contact smoking cessation intervention in an outpatient setting.", "Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.", "Stage-based expert systems to guide a population of primary care patients to quit smoking, eat healthier, prevent skin cancer, and receive regular mammograms.", "Long-term effectiveness of computer-generated tailored feedback in smoking cessation.", "The effects and use of maintenance newsletters in a smoking cessation intervention.", "A randomized controlled trial of multiple tailored messages for smoking cessation among callers to the cancer information service.", "Effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self-help materials: randomized controlled trial.", "The effectiveness of a directly mailed smoking cessation intervention to Australian discharged hospital patients.", "A randomized trial to increase smoking intervention by physicians. Doctors Helping Smokers, Round I.", "Evaluation of a treatment approach combining nicotine gum with self-guided behavioral treatments for smoking relapse prevention.", "The effectiveness of personally tailored computer-generated advice letters for smoking cessation.", "A 2-year self-help smoking cessation manual intervention among middle-aged Finnish men: an application of the transtheoretical model.", "The effectiveness of personalized smoking cessation strategies for callers to a Quitline service.", "Smoking cessation by mail: a comparison of standard and personalized correspondence course formats.", "Effectiveness of a cognitive behaviour therapy self-help programme for smokers in London, UK.", "A comparison of nursing interventions for smoking cessation in adults with cardiovascular health problems.", "Evaluating nicotine replacement therapy and stage-based therapies in a population-based effectiveness trial.", "A self-help smoking cessation program for inner-city African Americans: results from the Harlem Health Connection Project.", "Using tailored interventions to enhance smoking cessation among African-Americans at a community health center.", "Effectiveness of personalized written feedback through a mail intervention for smoking cessation: a randomized-controlled trial in Spanish smokers.", "A randomized trial of a self-help smoking cessation intervention in a nonvolunteer female population: testing the limits of the public health model.", "Computer-tailored smoking cessation intervention in a general population setting in Germany: outcome of a randomized controlled trial.", "Nicotine gum and self-help behavioral treatment for smoking relapse prevention: results from a trial using population-based recruitment.", "Multiple risk expert systems interventions: impact of simultaneous stage-matched expert system interventions for smoking, high-fat diet, and sun exposure in a population of parents.", "Computer tailored intervention for older smokers using transdermal nicotine.", "Self-help smoking cessation and maintenance programs: a comparative study with 12-month follow-up by the American Lung Association.", "Format and quitting instructions as factors influencing the impact of a self-administered quit smoking program.", "An investigation of a minimal contact brand fading program for smoking treatment.", "Telephone counseling for population-based smoking cessation.", "Use of a self-help smoking cessation manual as an adjunct to advice from a respiratory specialist.", "Behavioral self-help materials as an adjunct to nicotine gum.", "The effectiveness of a postal smoking cessation 'kit'.", "Immediate and delayed effects of postal advice on stopping smoking.", "Nurse-assisted counseling for smokers in primary care." ]

[ "To examine the population impact and effectiveness of the Pro-Change smoking cessation course based on the Transtheoretical Model (TTM) compared to standard self-help smoking cessation literature.\n Randomized controlled trial.\n Sixty-five West Midlands general practices.\n Randomly sampled patients recorded as smokers by their general practitioners received an invitation letter and 2471 current smokers agreed.\n Responders were randomized to one of four interventions. The control group received standard self-help literature. In the Manual intervention group, participants received the Pro-Change system, a self-help workbook and three questionnaires at 3-monthly intervals, which generated individually tailored feedback. In the Phone intervention group, participants received the Manual intervention plus three telephone calls. In the Nurse intervention group, participants received the Manual intervention plus three visits to the practice nurse.\n Biochemically confirmed point prevalence of being quit and 6-month sustained abstinence, 12 months after study commencement.\n A total of 9.1% of registered current smokers participated, of whom 83.0% were not ready to quit. Less than half of participants returned questionnaires to generate second and third individualized feedback. Telephone calls reached 75% of those scheduled, but few participants visited the nurse. There were small differences between the three Pro-Change arms. The odds ratio (95% confidence intervals) for all Pro-Change arms combined versus the control arm were 1.50 (0.85-2.67) and 1.53 (0.76-3.10), for point prevalence and 6-month abstinence, respectively. This constitutes 2.1% of the TTM group versus 1.4% of the control group achieving confirmed 6-month sustained abstinence.\n There was no statistically significant benefit of the intervention apparent in this trial and the high relapse of quitters means that any population impact is small.", "This study examines the efficacy of targeted versus standard care smoking cessation materials among urban African American smokers. Five hundred smokers (250 to each group) are randomized to receive a culturally targeted or standard care videotape and print guide. Both groups receive 8 weeks of nicotine patches and reminder telephone calls at Weeks 1 and 3. Process outcomes include material use and salience at 1 and 4 weeks postbaseline. Smoking outcomes include 7-day abstinence, smoking reduction, and readiness to quit at 4 weeks and 6 months postbaseline. Despite greater use of the targeted guide (68.8% vs. 59.6%, p < .05), intervention participants do not perceive the targeted materials as more salient, and no significant differences are found between groups on the smoking outcomes. Findings point to the importance of greater audience segmentation and individual tailoring to better match intervention materials to the needs of the priority population.", "In a unique approach to utilizing an existing intervention, \"opportunistic\" and targeted school-based strategies were used to enroll 446 adults into a tailored preventive health program featuring a health screening and smoking-cessation intervention. Implemented through a public school district serving a multi-ethnic low-to-middle income urban community, subjects in this randomized trial were interviewed at enrollment and at three-, six-, and 12-month follow-up, and rescreened at 12 months, to assess changes in smoking-related knowledge, attitudes, and practices. Using conservative assumptions, self-reported ever-quit rates and continuous abstinence rates of 57.5% and 2.6%, respectively, were achieved across groups; point-prevalence abstinence rates were 13.2%, 12.9%, and 10.3% at three, six, and 12 months. The study examines issues relevant to smoking status and stages of change in this population. The role of the school in increasing access to needed health programming in underserved communities is explored.", "Radon and cigarette smoking have synergistic effects on lung cancer, even when radon concentrations are relatively low. Working through an electric utility company, we sought to reach smoking households with low radon concentrations and motivate smoking cessation or prohibiting smoking in the home.\n Eligible homes (n = 714) were randomised to receive: (1) the Environmental Protection Agency's (EPA's) \"A citizen's guide to radon\"; (2) a specially developed pamphlet; or (3) that pamphlet plus brief telephone counselling.\n Utility company \"bill stuffers\" offered free radon test kits to smoking households. All households received radon test results with an explanatory cover letter. Both the specially developed pamphlet and the telephone counselling emphasised that smoking cessation or prohibiting smoking in the home were the optimal risk reduction strategies. Households were followed up at 3 and 12 months after receiving materials.\n The specially developed pamphlet and the EPA guide yielded similar outcomes. There was a non-significant trend for telephone counselling to produce greater sustained quitting than the specially developed pamphlet, and phone counselling led to significantly more new household smoking bans.\n Working through a public utility company is an efficient way to reach smoking households, and brief telephone counselling is a promising method for promoting household smoking bans and cessation in homes alerted to the risk posed by the combination of radon and smoking.", "This study compared interactive and noninteractive smoking cessation interventions for a population of smokers who were all members of 1 division of a managed care company. In addition, it examined whether a dose-response relationship existed. Screening was completed for 19,236 members who were contacted by telephone or mail. Of the 4,653 who were identified as smokers, 85.3% were enrolled. A 2 Intervention (interactive or noninteractive) x 4 Contacts (1, 2, 3, or 6 contacts) x 4 Occasions (0, 6, 12, and 18 months) design was used. The interactive intervention was stage-matched expert-system reports plus manuals; the noninteractive intervention was stage-matched manuals. Contact occurred in 1 of 4 series (1, 2, 3 or 6 contacts) at 3-month intervals. The expert system outperformed the stage-matched manuals, but there was no clear dose-response relationship for either intervention.", "Few smoking cessation self-help materials are available for smokers who are not planning to quit. However, computer-tailored interventions can be designed specifically for these smokers.\n In a large randomized field trial (N = 843), two different tailored smoking cessation self-help interventions (multiple tailoring and single tailoring) and one standardized smoking cessation self-help guide were compared with a no-information control group and with each other. The contents of the tailored interventions were adapted to individuals' self-reported stage of change, outcome expectations, self-efficacy levels, and smoking behavior.\n The primary outcome measure was forward stage transition. The standardized self-help guide had no effect. Among smokers who were not planning to quit within the next 5 years the multiple-tailored intervention was more effective than the single-tailored intervention. This pattern was supported by the cognitive changes caused by the interventions. Among smokers who were planning to quit within the next 5 years but not within the next 6 months, none of the self-help materials had any effect.\n The present results show that the self-help material currently available in the Netherlands, the standardized self-help guide, was not effective among smokers with low readiness to change. However, computer-generated tailored interventions seem a promising means of communicating information on smoking and smoking cessation to these smokers.", "A total of 424 smokers were randomized in a 2 x 2 factorial experiment. A pharmacologic factor contained 2 levels: transdermal nicotine path (TNP; 21 mg) and placebo. A self-help behavioral treatment factor contained 2 levels: video-enhanced self-help treatment manual and self-help treatment manual only. At 2 months, TNP produced a higher level of abstinence (36%) than placebo (20%), p < .001. No other comparison was significant. In secondary analyses, (at 2 months) and compliance with patch treatment regimen (at 2, 6, and 12 months) were associated with less relapse. Although nicotine replacement therapy has improved our ability to produce smoking cessation, the production of sustained, longer term abstinence remains an elusive goal.", "Smokers (N = 756) were randomly assigned by stage of change to (a) standardized self-help manuals (ALA+ condition), (b) individualized manuals matched to stage (TTT condition), (c) interactive expert-system computer reports plus individualized manuals (ITT condition), or (d) a personalized condition with 4 counselor calls, stage manuals, and computer reports (PITT condition). Over 18 months, the ITT group's results more than doubled those of the ALA+ group on abstinence measures. The ALA+ and TTT conditions were equivalent over 12 months, but at 18 months the TTT condition was more effective. The ITT condition was the best or comparable with the best treatment at all follow-ups for smokers at all stages of change. Results suggest that an effective expert system has been developed, and discussion focuses on delivering this system to entire populations of smokers.", "Radon and cigarette smoking have synergistic effects on lung cancer risk. Electric utility company bill stuffers offered free radon test kits to households with at least one smoker. Participating households (n = 1364) were randomized within a 2 x 2 design to evaluate the main effects of brief telephone counseling and a targeted video on smoking cessation and the establishment of new household smoking bans. Phone counseling was associated with cessation at 3-month follow-up but neither intervention led to 12-month or sustained cessation. While neither intervention had a significant effect on new bans, there were trends in the predicted direction and the combination of the two significantly increased new bans compared with no intervention. The presence of children in the household was associated with new bans. While few households had high levels of radon, such levels were associated with radon mitigation behaviors. Together with a previous study, these results suggest radon risk is a useful and inexpensive way to engage smoking households in risk reduction behaviors, especially the institution of household smoking bans.", "A stage-matched expert system intervention was evaluated on 4144 smokers in a two-arm randomized control trial with four follow-ups over 24 months. Smokers were recruited by random digit-dial calls, and 80.0% of the eligible smokers were enrolled. Individualized and interactive expert system computer reports were sent at 0, 3, and 6 months. The reports provided feedback on 15 variables relevant for progressing through the stages. The primary outcomes were point prevalence and prolonged abstinence rates. At 24 months, the expert system resulted in 25.6% point prevalence and 12% prolonged abstinence, which were 30% and 56% greater than the control condition. Abstinence rates at each 6-month follow-up were significantly greater in the Expert System (ES) condition than in the comparison condition with the absolute difference increasing at each follow-up. A proactive home-based stage-matched expert system smoking cessation program can produce both high participation rates and relatively high abstinence rates.", "Personalized feedback and a financial incentive, developed from an intrinsic/extrinsic motivation framework, were evaluated as adjuncts to self-help materials for smoking cessation. Ss (N = 1,217) were randomized to 4 treatment groups and were followed up at 3 and 12 months. Consistent with hypotheses derived from the motivation framework, the financial incentive increased the use of self-help materials, did not increase cessation rates among program users, and was associated with higher relapse rates among those who did manage to quit. The personalized feedback increased both smoking cessation and use of the materials 3 months after distribution of the materials. Continuous abstinence (abstinence at 3 and 12 months) in the group that received the personalized feedback alone was twice the rate of the other groups.", "Previous research has demonstrated the efficacy of an interactive expert system intervention for smoking cessation for a general population. The intervention provides individualized feedback that guides participants through the stages of change for cessation. Enhancing the expert system by adding proactive telephone counseling or a stimulus control computer designed to produce nicotine fading could produce preventive programs with greater population impacts.\n Four interventions were compared: (a) the interactive expert system intervention; (b) the expert system intervention plus counselor calls; (c) the expert system intervention plus the stimulus control computer; and (d) an assessment only condition. A 4 (intervention) x 4 (occasions) (0,6,12, and 18 months) design was used. Smokers were contacted at home via telephone or mail. The initial subject pool was the 24,178 members of a managed care company. Screening was completed for 19,236 members (79.6%), of whom 4,653 were smokers; 85.3% of the smokers were enrolled.\n Thirty-eight percent were in the precontemplation stage, 45% in the contemplation stage, and only 17% in the preparation stage. At 18 months, the expert system resulted in 23.2% point prevalence abstinence, which was 33% greater than that of assessment only. The counselor enhancement produced increased cessation at 12 months but not at 18 months. The stimulus control computer produced no improvement, resulting in 20% worse cessation rates than the assessment only condition.\n The enhanced conditions failed to outperform the expert system alone. The study also demonstrated the ability of the interactive expert system to produce significantly greater cessation in a population of smokers than assessment alone.\n Copyright 2000 American Health Foundation and Academic Press.", "Most smokers attempt to stop smoking without using help. We evaluated the efficacy of a decision aid to motivate quitters to use efficacious treatment. SETTING AND PARTICIPANTS, A total of 1,014 were recruited from a convenience sample of 3,391 smokers who intended to quit smoking within 6 months. DESIGN AND Smokers were assigned randomly to either receive the decision aid or no intervention. The decision aid was expected to motivate quitters to use efficacious cessation methods and contained neutral information on treatment methods, distinguishing between efficacious and non-efficacious treatments. MEASUREMENTS Baseline questionnaire and follow-ups were used 2 weeks and 6 months after the start of the intervention.\n The decision aid increased knowledge of cessation methods and induced a more positive attitude towards these methods. Furthermore, 45% reported increased confidence about being able to quit and 43% said it helped them to choose between treatments. However, no clear effect on usage of treatment aids was found, but the intervention group had more quit attempts (OR=1.52, 95% CI 1.14-2.02) and higher point prevalence abstinence at 6-month follow-up (20.2% versus 13.6%; OR=1.51, 95% CI=1.07-2.11). CONCLUSIONS An aid to help smokers decide to use efficacious treatment when attempting to quit smoking had a positive effect on smoking cessation, while failing to increase the usage of efficacious treatment. This finding lends support to the notion that the mere promotion of efficacious treatments for tobacco addiction might increase the number of quit attempts, irrespective of the actual usage of treatment.", "The incremental effects of (a) a self-help booklet alone, (b) self-help booklet with computer-generated personalized feedback, and (c) self-help booklet, personalized feedback, and outreach telephone counseling were evaluated in a population-based, nonvolunteer sample of smokers. Smokers (N = 1,137) were identified through a telephone survey of a random sample of 5,903 enrollees in a health maintenance organization and randomized to a no-treatment control group or 1 of the 3 intervention conditions. Smoking status was ascertained 3, 12, and 21 months postrandomization. Cotinine validation of self-reported cessation was obtained at the 12-month follow-up. Overall, the telephone counseling significantly increased smoking cessation at the 3-month follow-up, but not at 12 or 21 months. Among smokers who were precontemplative at baseline, telephone counseling significantly increased prevalent abstinence at 3 and 12 months and continuous abstinence at 21 months (defined as self-reported abstinence at 3, 12, and 21 months).", "nan", "Smokers requesting self-help materials for smoking cessation (N = 2,021) were randomized to receive (a) an experimental self-quitting guide emphasizing nicotine fading and other nonaversive behavioral strategies, (b) the same self-quitting guide with a support guide for the quitter's family and friends, (c) self-quitting and support guides along with four brief counselor calls, or (d) a control guide providing motivational and quit tips and referral to locally available guides and programs. Subjects were predominantly moderate to heavy smokers with a history of multiple previous quit attempts and treatments. Control subjects achieved quit rates similar to those of smokers using the experimental quitting guide, with fewer behavioral prequitting strategies and more outside treatments. Social support guides had no effect on perceived support for quitting or on 8- and 16-month quit rates. Telephone counseling increased adherence to the quitting protocol and quit rates.", "African Americans remain a critically underserved group for smoking cessation interventions. This study tested the effectiveness of a tailored, culturally sensitive intervention for African American smokers who called the NCI Cancer Information Service (CIS) for help to quit smoking.\n This paper presents results of a 2-year study of tailored counseling strategies among African American smokers (n = 1,422) who called four regional CIS offices in response to a radio-based media campaign in 14 communities. Callers were randomly assigned to receive either the standard CIS quit smoking counseling and guide (Clearing the Air) or counseling and a guide (Pathways to Freedom) tailored to the quitting needs and barriers of African American smokers. Callers were predominantly female (63.6%). ages 20-49 (88%), with a high school education or more (84%). Median smoking history was 17 years; median smoking rate was 20 cigarettes/day. Standard (n = 689) and Tailored (n = 733) group subjects did not differ on most baseline measures.\n On most measures, Standard and Tailored counseling/guides received similar ratings, but the Tailored guide was rated as having more appealing photos (P = 0.001) and as being more appropriate for family members (P = 0.003). Six-month follow-up with 893 subjects (response rates were 63% Standard, 62% Tailored, ns) showed significantly more quit attempts (P = 0.002) and greater use of prequitting strategies (P < 0.05) among Tailored than among Standard subjects, but no differences in self-reported 1-week abstinence (14.4% Standard, 16.2% Tailored) (ns). An opportunistic 12-month follow-up of subjects recruited in the last year of the study (n = 445) (response rates were 57% Standard, 60% Tailored, ns) showed a significantly higher quit rate (15.4% Standard, 25.0% Tailored) for Tailored subjects (P = 0.034).\n Results show promise for tailored approaches to boost quit attempts and success rates among African American smokers.\n Copyright 1998 American Health Foundation and Academic Press.", "Examine the effects of three iterative tailored feedback letters addressing smoking; physical activity; and fruit, vegetable, and fat intake, and test the additional effects of providing feedback on action plans.\n A tailored, print-based intervention was developed and tested in a randomized control trial with a posttest after 9 months.\n A total of 2827 respondents agreed to participate. They were recruited from a random sample of 35,000 addresses obtained through the Dutch national telephone company.\n The mean age was 49 years, and 55% were female. Intervention. The experimental group received three printed tailored letters, and the control group received three printed generic letters. Respondents from the experimental group randomly received either a third letter with tailored information or tailored information and action-planning feedback. MEASURES; The questionnaire assessed physical activity; smoking; consumption of fruit, vegetables and fat; motivational determinants; action plans; and demographics.\n Tailored information resulted in more improvement over time than generic information for the intake of fruit, vegetables, and fat and for physical activity. No differences between the conditions were found for smoking because of high cessation rates in all conditions. Action-planning feedback did not increase the effects.\n Tailored lifestyle information can be effective for adults in changing nutrition behavior and physical activity.", "nan", "This worksite study assesses the relative effectiveness of three smoking cessation programs. Computerized medical files indicated that 29% of 13,171 employees were current smokers. Of smokers responding to a worksite-wide survey, 79% indicated interest in a smoking cessation program; 402 smokers agreed to participate and were randomly allocated, within their preference for a group or self-help approach, to the three different programs. Overall, 11% of smokers participated, an excellent rate for a large worksite. Participants were followed for 12 months (91% follow-up). Smokers in the group preference had better short-term results than did those following the self-help approach. The Multiple Component Program had 61% who quit, the Relapse Prevention Program had 37%, and the American Cancer Society Quitter's Guide had 12%. Long-term quit rates ranged from 16% to 26%; all groups exceeded the usual spontaneous quit rate of 5%.", "This study evaluated the effectiveness of nicotine chewing gum in smoking cessation, when incorporated into a behaviorally oriented self-help program. One hundred ninety-seven patients were randomly assigned to nicotine gum with a self-help manual, a self-help manual without gum, or a control condition, but received no further treatment from the prescribing physician. At six weeks, the nicotine gum group was superior to both the self-help and control conditions. By one year, many gum patients had relapsed, and the treatment effect was no longer significant. Patients who were able to quit initially were most likely to remain ex-smokers in the self-help condition. The clinical importance of these findings is discussed.", "At two chest clinics 1206 cigarette smokers referred by their general practitioners for chest radiography only either were dealt with in the normal way or in addition were given a How to Stop Smoking booklet by the clinic receptionist or nurse. Follow up one year later showed that 3.2% of all patients had successfully given up smoking, older patients doing better than younger ones and men doing better than women. Overall 3.9% of the group receiving a booklet were successful compared with 2.7% of the controls (p = 0.14). At one clinic the groups were not well matched for age but at the other, where there was no such imbalance, there was a suggestion that the booklet group did better than the controls (6.5% v 2.7% success), although the difference did not achieve conventional statistical significance (p = 0.09). If this can be confirmed as a real effect then this cheap, simple strategy could easily be applied on a large scale.", "To develop and evaluate, in a primary care setting, a computerised system for generating tailored letters about smoking cessation.\n Randomised controlled trial.\n Six general practices in Aberdeen, Scotland.\n 2553 smokers aged 17 to 65. Interventions: All participants received a questionnaire asking about their smoking. Participants subsequently received either a computer tailored or a non-tailored, standard letter on smoking cessation, or no letter.\n Prevalence of validated abstinence at six months; change in intention to stop smoking in the next six months.\n The validated cessation rate at six months was 3.5% (30/857) (95% confidence interval 2.3% to 4.7%) for the tailored letter group, 4.4% (37/846) (3.0% to 5.8%) for the non-tailored letter group, and 2.6% (22/850) (1.5% to 3.7%) for the control (no letter) group. After adjustment for significant covariates, the cessation rate was 66% greater (-4% to 186%; P=0.07) in the non-tailored letter group than that in the no letter group. Among participants who smoked <20 cigarettes per day, the cessation rate in the non-tailored letter group was 87% greater (0% to 246%; P=0.05) than that in the no letter group. Among heavy smokers who did not quit, a 76% higher rate of positive shift in \"stage of change\" (intention to quit within a particular period of time) was seen compared with those who received no letter (11% to 180%; P=0.02). The increase in cost for each additional quitter in the non-tailored letter group compared with the no letter group was pound 89.\n In a large general practice, a brief non-tailored letter effectively increased cessation rates among smokers. A tailored letter was not effective in increasing cessation rates but promoted shift in movement towards cessation (\"stage of change\") in heavy smokers. As a pragmatic tool to encourage cessation of smoking, a mass mailing of non-tailored letters from general practices is more cost effective than computer tailored letters or no letters.", "There have been few community-based randomized, controlled intervention trials for cessation in high-risk smokers. In such a trial we evaluated the effects of postal smoking cessation advice in smokers with asbestos exposure and/or reduced forced expiratory volume in one second (FEV1). All men aged 30-45 yrs (n=22,392) living in 34 municipalities in western Norway were invited to a cross-sectional community survey. Information on smoking habits and occupational asbestos exposure were obtained from self-administered questionnaires and measurements of FEV1 were performed with dry-wedge bellow spirometers. Among 16,393 participants we identified a group of 2,610 smokers with previous occupational asbestos exposure and/or adjusted FEV1 in the lowest quartile. A random half (n=1,300) received a mailed personal letter from a respiratory physician with a person-specific health advice to quit smoking and a pamphlet on smoking cessation. The remaining smokers (n=1,310) acted as controls and did not receive any information. Twelve months after the intervention, information on smoking habits was re-examined using a postal questionnaire. Among the respondents (n=2,282), smoking cessation was reported altogether by 13.7% in the intervention group versus 9.9% in the control group (p<0.01). The 1 yr sustained quit rate (no smoking at all during the last year) was 5.6 versus 35% (p<0.05), respectively. Measurements of carbon monoxide in expired air (with < or = 10 parts per million) confirmed self-reported nonsmoking in samples of the two groups. In a community this simple postal smoking cessation advice from a respiratory physician based on person-specific risk factors improved the 1 yr sustained success rate by 60% in identified high-risk smokers.", "Public health and hospital nurses have widespread contact with smokers; an effective smoking cessation program administered by nurses has tremendous potential. This study evaluated: 1) the effectiveness of the self-help cessation program, \"Time to Quit\"/\"Moi aussi, j'écrase\" (TTQ), provided on a one-to-one basis; and 2) a smoking cessation training program for baccalaureate nursing students. Nursing students recruited 307 smokers who were randomly assigned to receive one of two interventions. Control smokers received a list of community smoking cessation resources and experimental subjects received this list plus TTQ. Smoking self-reports and cotinine levels were obtained at baseline, six weeks and nine months. More smokers receiving TTQ had reduced at six weeks post-intervention, while there were no differences in quit or reduction rates at the nine-month follow-up. Students were positive about learning the techniques and their knowledge scores were significantly higher than those of non-participating students.", "Using a complete factorial design, we tested three interventions for smoking cessation in routine primary care practice. The interventions tested were 1) physician counseling, 2) mailed letters and educational materials designed by the National Cancer Institute (NCI), and 3) referral to smoking cessation classes. Thirty-seven family practice physicians at three of Group Health's outpatient facilities participated. Patient participation rates were 95%, and follow-up was complete for 92% of those participating. None of the interventions had any effect on point prevalence of quitting as determined 8-9 months later by self-report. However, the combination of physician counseling and NCI materials doubled the odds of occurrence of significant antismoking behavior (quit, quit and relapse, or cut down) during the ensuing 8-9 months in those individuals receiving that combination. Referral to smoking cessation classes was strikingly ineffective in this setting. Of 369 individuals designated by study design for referral, only 14% even investigated the classes. This compares with a 10% self-referral rate for those persons not designated for referral by our study design. Our results and other recent work suggest that more intensive interventions on multiple occasions based on relapse prevention strategies hold promise for future success in smoking cessation efforts in primary care.", "This study demonstrated the effectiveness of a computer-delivered smoking cessation program for the worksite. 58 VA Medical Center employees were randomly assigned to a computer group (computerized nicotine fading and stop-smoking contest) or a contest-only group. In comparison with the contest-only group, the computer group had nonsignificantly higher abstinence rates across follow-up, had marginally lower CO levels at the 3- and 6-month follow-ups, and smoked cigarettes with lower nicotine levels at the 10-day and 6-month follow-ups.", "Randomized controlled trials of smoking interventions have not been well-documented for lung cancer screening populations. In this study, we randomly assigned 171 current smokers who were undergoing low-dose fast spiral chest CT (SCTS) for lung cancer screening to receive either standard written self-help materials or a written list of Internet resources for smoking cessation. At the 1-year follow-up, more of the subjects receiving Internet-based resources reported making a stop attempt (68% versus 48%, P=0.011). However, there were no statistically significant differences in 7-day point prevalence quit rates (5% versus 10%) or advancement in motivational readiness to stop smoking (27% versus 30%), respectively, between the groups. Clearly, more investigation is warranted into how to tailor smoking interventions for cancer screening participants.", "The current study evaluated the effectiveness of widely used self-help materials for quitting smoking. Five hundred and seventy smokers volunteered during a baseline survey to participate in the evaluation. After random assignment, 200 were mailed National Cancer Institute (NCI) \"Quit for Good\" materials, 200 the Minnesota \"Quit and Win\" program, and the remaining 170 were assigned to a nonintervention control condition. Results at 7-month follow-up failed to indicate treatment effects either for abstinence or for reported quit attempts. A number of smokers quit prior to the mailing of self-help materials, suggesting that a telephone prompt in itself may have been an important stimulus to cessation. Overall abstinence at follow-up was 10%. Contrary to expectation, successful participants were less likely to use a number of specific preparation strategies for quitting. The results are instructive in providing a large-scale assessment of self-help materials in a population of smokers that was not specifically seeking treatment.", "It has been suggested that tailoring self-help materials for specific target populations will increase their effectiveness. This study tested the value of a self-help guide tailored specifically for women with young children. These women were recruited through a media campaign that encouraged smokers to call the Cancer Information Service (CIS) for assistance in stopping smoking. Women smokers with young children (under the age of 6) who called the CIS were given telephone counseling on quitting and were mailed one of three stop smoking guides. One third of callers received Quitting Times, a guide written specifically for women with young children; one third received the American Lung Association guide, Freedom from Smoking for You and Your Family; and one third received Clearing the Air, a guide developed by the National Cancer Institute. Six months after calling the CIS, these women were contacted by telephone to assess changes in smoking behavior. Overall, 12.5% of the women reported not smoking for at least 1 week at the time of the 6-month follow-up interview. There were no significant differences between subjects in the three groups in use of the self-help guides, methods used to attempt quitting, and quitting behavior. Findings from this study do not support the hypothesis that using a tailored stop smoking guide increases the targeted audience's cessation rate or affects quitting-related behavior. However, it should be noted that the smokers who called were predominantly in the contemplation or action stages.", "We examined the ability of a provider-initiated, minimal-contact intervention to modify the smoking behavior of ambulatory clinic patients. Smokers at two outpatient sites were assigned to one of three groups: provider intervention only (PI); provider intervention plus self-help manual (PI/M); and usual care (control) group (C). The physician message emphasized the patient's personal susceptibility, the physician's concern, and the patient's ability to quit (self-efficacy). The nurse consultation concentrated on benefits and barriers associated with stopping, and on strategies for cessation. Telephone interviews were conducted with the 250 participants within a few days of their clinic visit and again at one and six months. Both PI and PI/M proved to be superior to usual care in motivating attempts to quit at both one-month and six-month follow-ups, and logistic regression analyses indicated that participants receiving the self-help manual in addition to the health provider message were between two and three times more likely to quit smoking during the study period than were participants in either of the other study groups.", "To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly.\n Quasi-randomized controlled trial.\n A total of 34 randomly selected general practices from a German region (participation rate 87%).\n A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%).\n The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change.\n Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups.\n Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up.\n The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.", "Treating multiple health behavior risks on a population basis is one of the most promising approaches to enhancing health and reducing health care costs. Previous research demonstrated the efficacy of expert system interventions for three behaviors in a population of parents. The interventions provide individualized feedback that guides participants through the stages of change for each of their risk behaviors. This study extended that research to a more representative population of patients from primary care practice and to targeting of four rather than three behaviors.\n Stage-based expert systems were applied to reduce smoking, improve diet, decrease sun exposure, and prevent relapse from regular mammography. A randomized clinical controlled trial recruited 69.2% of primary care patients (N = 5407) at home via telephone. Three intervention contacts were delivered for each risk factor at 0, 6, and 12 months. The primary outcome measures were the percentages of at-risk patients at baseline who progressed to the action or maintenance stages at 24-month follow-up for each of the risk behaviors.\n Significant treatment effects were found for each of the four behaviors, with 25.4% of intervention patients in action or maintenance for smoking, 28.8% for diet, and 23.4% for sun exposure. The treatment group had less relapse from regular mammography than the control group (6% vs. 10%).\n Proactive, home-based, and stage-matched expert systems can produce relatively high population impacts on multiple behavior risks for cancer and other chronic diseases.", "Although tailored interventions consisting of only a few pages of information lead to more quitting than no intervention in the short term, the long-term efficacy of a single tailored intervention still has to be proven. In the present study smokers were reactively recruited and randomly allocated to one of four intervention conditions: (1) outcome information, (2) self-efficacy enhancing information, (3) both sorts of information or (4) no information. Smokers in the three experimental groups received computer-generated tailored feedback containing the condition-specific information, by mail. The results from the 14 months follow-up can be summarized as follows. Compared to the no information condition, all three experimental conditions led to significantly more smokers who had engaged in 24-h quit attempts. However, no experimental condition led to more 7-day quitting than the no information condition. With regard to continuous abstinence, the experimental condition offering a combination of outcome information and self-efficacy enhancing information had a significant effect, compared to the no information condition. It is concluded that a minimal six-page tailored intervention can be beneficial in supporting smokers to quit smoking, even after 14 months.", "This article evaluates the effects and use of adjuncts to a televised smoking cessation program, based on the American Lung Association's \"Freedom From Smoking in 20 Days.\" Subjects were randomized to maintenance and control conditions. The maintenance condition received newsletters with information and support addressing different stages in the cessation process and information about a telephone hotline. The maintenance condition did not increase cessation at any wave of interviewing, assessed by multiple point or point prevalence of abstinence. Those abstinent at 6 months and those who had made an attempt to stop smoking by that time were more likely to have used the newsletters and were more likely to have used the sections relevant to their cessation stage. Rates of use of the telephone hotline were low. The newsletters appear to be useful to smokers who are predisposed to use written materials.", "Self-help materials computer-tailored to the specific needs of smokers have shown promise as a high-reach, low-cost intervention for smoking cessation. Adding tailored cessation materials to telephone-based cessation counseling may be a way of generating greater efficacy in promoting and maintaining cessation. The objective of this study is to assess the efficacy of adding different types of behavioral smoking cessation materials to brief telephone-based cessation counseling.A total of 1,978 smokers calling the National Cancer Institute's (NCI's) Cancer Information Service (CIS) for help in quitting smoking initially received brief cognitive-behavioral cessation counseling from a CIS information specialist. Following a baseline interview administered by the information specialist, subjects were randomly assigned to one of four conditions, each delivered by U.S. mail: a single, untailored smoking cessation guide (SU); a single, tailored smoking cessation guide (ST); a series of four (multiple) printed materials tailored only to baseline data (MT); and a series of four (multiple) printed materials tailored to baseline as well as retailored using 5-month interim progress data (MRT). The primary outcome measure was 7-day point prevalence abstinence rates assessed using a computer-assisted telephone interview (CATI) at 12-month follow-up.At 12-month follow-up, using intent-to-treat, imputed, and per-protocol analyses, no differences were found among the four experimental conditions (linear trend), or when the ST, MT, and MRT groups were compared with the control (SU) group. Participants in the two multiple message group conditions combined (MT + MRT), however, had significantly higher abstinence rates than participants in the two single message group conditions combined (SU + ST). Moreover, among subjects who reported quitting at the 5-month follow-up, participants receiving the MRT materials reported higher abstinence rates at 12 months than the other three groups combined (SU + ST + MT). The results of this study support the effectiveness, over and above a single telecounseling interaction, of multiple tailored print material contacts on cessation. These effects, however may be due to tailoring, or the longitudinal nature of the two multiple tailored conditions, or both. The strongest evidence for tailoring occurred in the MRT condition for relapse prevention, suggesting that print materials tailored to interim progress may be especially effective in this context. The qualities of specific psychosocial and communication elements in tailored materials should receive attention in future research.", "To evaluate the effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self-help materials.\n Randomized controlled trial.\n The UK Quitline.\n A total of 1508 current smokers and recent ex-smokers.\n The control group received usual care (telephone counselling and an information pack sent through the post). The intervention group received in addition a computer-generated individually tailored advice letter.\n All outcomes were assessed at 6-month follow-up. The primary outcome measure was self-reported prolonged abstinence for at least 3 months. Secondary outcomes were self-reported prolonged abstinence for at least 1 month and 7-day and 24-hour point-prevalence abstinence.\n For the sample as a whole, quit rates did not differ significantly between the two conditions. However, among the majority (n = 1164) who were smokers at baseline, quit rates were consistently higher in the intervention group: prolonged abstinence for 3 months, 12.2% versus 9.0% [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 0.96-2.04, P = 0.080); prolonged abstinence for 1 month, 16.4% versus 11.3% (OR = 1.53, 95% CI = 1.09-2.15, P = 0.013); 7-day point-prevalence abstinence, 18.9% versus 12.7% (OR = 1.59, 95% CI = 1.15-2.19, P = 0.004); 24-hour point-prevalence abstinence, 20.9% versus 15.4% (OR = 1.45, 95% CI = 1.07-1.96, P = 0.015).\n The results for the smokers are encouraging in showing a small but useful effect of the tailored letter on quit rate. Versions of the tailoring program could be used on the web and in general practices, pharmacies and primary care trusts.", "The objective was to assess the effectiveness of a directly mailed smoking cessation intervention to discharged hospital patients.\n A randomized controlled trial was used. In the 2 weeks after discharge, smokers in the intervention group were sent by mail a personally addressed letter from their medical consultant urging them to quit plus a self-help quitting manual, and smokers in the control group received usual care. Patients were surveyed about their smoking status at 6 and 12 months after discharge. A total of 1858 discharged patients responded to both questionnaires. The main outcome measures were self-reported smoking in past week at 6 and 12 months after discharge. Quitters at 12 months were biochemically tested for evidence of smoking.\n The results failed to show that smoking cessation advice directly mailed to a broad cross-section of discharged hospital patients who smoke led to smoking cessation. However, the intervention increased cessation among smokers with medical conditions for which quitting is highly relevant. In general, patients who were more likely to quit were older, had entered the hospital as an emergency case, and had a medical diagnosis for which quitting is highly relevant.\n This study suggests that hospital patients who smoke and are also diagnosed with conditions which call for quitting are more likely to quit if they receive from their consultant a personalized letter advising them to quit and a self-help manual.\n Copyright 1999 American Health Foundation and Academic Press.", "Sixty-six physicians were randomized to three groups to conduct a 1-month campaign to help their patients stop smoking. The workshop group received free patient education materials and a 6-hour training workshop. The materials group received free patient education materials, and the no-assistance group received nothing. A telephone interview was completed with 89% of the 6767 eligible adult patients seen during the month of the campaign. The brief training program and patient education materials marginally increased the smoking intervention activities of volunteer physicians in private practice. Both workshop and materials physicians asked 54% of their smoking patients to stop; no-assistance physicians asked 40%. One year later, 36% of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking. If the physician had asked the patient if he or she smoked, the probability of a quit attempt was 47%. Patients who had been asked if they smoked were more likely to claim to have stopped (13%) than patients who had not been asked (9%). However, the proportion of patients claiming continued abstinence (range, 12% to 14%) was not related to the group of the physician.", "1,218 smokers able to quit smoking for 48 hr were randomly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment. A pharmacologic factor contained four levels: nicotine polacrilex (gum) delivered ad lib or on a fixed regimen, placebo gum, and no gum. A self-guided behavioral treatment factor contained three levels: self-selected relapse prevention modules, randomly administered modules, and no modules. Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups. The fixed regimen accounted for most of the effect for gum. There was no effect for the relapse prevention module factor. Men and women showed a differential treatment response. Men who received nicotine gum were more likely to be abstinent at each follow-up (2, 6, and 12 months). No treatment was significantly better among women. We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed.", "To assess the effectiveness of a new computer-generated tailored advice programme designed to be used by smokers and recent quitters having problems staying stopped.\n Randomized trial comparing a series of questionnaire assessments leading to tailored computer-generated advice letters mailed at strategically relevant times, to a no extra treatment control sent standardized printed self-help materials.\n Victoria, Australia.\n A total of 1058 smokers or recent quitters recruited from callers to the Quitline.\n Smoking status and sustained abstinence at 12-month follow-up, plus extent of participation in the intervention.\n Using a conservative analysis (missing data coded as a treatment failure), 6-month sustained abstinence was reported by significantly more participants in the computer-generated tailored advice (20%) than the standard printed materials condition (12%) at 12-month follow-up OR 1.82 (1.31-2.55)). Group differences in point prevalence abstinence (28% intervention, 25% control) were not significant. Among participants in the tailored advice condition, 6-month sustained abstinence was associated with the number of advice letters received.\n The provision of a series of tailored, computer-generated advice letters resulted in greater rates of sustained cessation than for controls. A dose-response relationship was found, with increased compliance with the intervention associated with improved cessation outcomes. The programme appears to have much of its effect by preventing relapse.", "A 2-year self-help manual smoking cessation intervention was conducted among a panel of middle-aged Finnish men (n = 265) who were recruited proactively in a longitudinal cardiovascular risk factor surveillance study.\n Intervention utilized the stages of change concept of the transtheoretical model. The stages were assessed in the treatment condition at baseline of the cessation study and after that by mail every sixth month. Assessments were followed by an immediate mailing of a stage-based self-help manual matching the stage of change at that time. A usual care group was assessed annually but received no treatment.\n A significant time x intervention effect (P < 0.05) and time x baseline stage effect (P < 0.001) on quit rates were observed in the panel data over the 2-year period. An analysis of changes in the stages of change also revealed an accelerated cessation process in the treatment condition.\n We conclude that mailed stage-matched self-help smoking cessation manuals were able to accelerate the smoking cessation process but manuals alone may not constitute a sufficient long-term intervention. The effects of differential exposure to intervention, subject characteristics, measurement reactivity, and secular trends are discussed as potential confounds.", "To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation.\n Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months.\n Victoria, Australia.\n A total of 1578 smokers who called the Quitline service and agreed to participate.\n Smoking status at follow-up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service.\n At the 3-month follow-up, significantly more (chi2(2) = 16.9; P < 0.001) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer-generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12-month follow-up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer-generated tailored advice.\n Computer-generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice.", "Self-Instructional behavior-change programs for reducing risks to health are potentially widely available, acceptable and cost-effective. This paper reports outcomes of a smoking cessation program administered by mail. Two hundred and eight smokers were allocated systematically to a quit kit control condition (n = 40), to a standard correspondence course (n = 86) and to a personalized correspondence course prepared with the aid of a microcomputer (n = 82). There were significantly higher rates of abstinence after the course for correspondence course participants compared to controls, but these differences did not persist at three-month and nine-month follow-ups. There were no differences between the personalized and standard courses on abstinence rates, number of cigarettes smoked per day, or return of feedback forms on each lesson. There were associations between self-efficacy strength and reduced rates of smoking, and active participation in the course was associated with lower smoking rates.", "One of the key goals of health promotion strategies in the UK and other developed countries is to reduce the prevalence of cigarette consumption. While overall smoking rates in the UK have fallen over the last few decades, they have barely fallen for the least advantaged adults (Department of Health, 1998a). There is a need for interventions that are suitable for lower socio-economic status (SES) smokers that have undergone rigorous evaluation. This study describes a randomized controlled trial of cognitive behaviour therapy (CBT) with smokers from a deprived area of London. At 6 months follow-up, 21 (17.2%) of 122 participants receiving therapy were abstinent and 14 (11.5%) had reduced cigarette consumption by at least 25% of pre-treatment level. Six (5.6%) of 107 participants in the control group were abstinent and none had reduced consumption. These results suggest that this self-help CBT intervention has the potential to reduce the prevalence of smoking among lower SES smokers.", "To examine the relative effectiveness of three different presentations of a smoking cessation program on the smoking behavior of adults with cardiovascular health problems.\n A 2 x 2 x 2 x 4 experimental design with stratification by sex, smoking history, and a cardiovascular event, and randomization to Individual, Group, Written, or No Intervention groups.\n Six community hospital classrooms.\n 255 nonhospitalized adults. THEORETIC FRAMEWORK: Interaction Model of Client Health Behavior.\n Study Intake: Professional referral form, demographic questionnaire, smoking habits questionnaire, health history, perceived threat survey, perceived health status. Follow up: smoking cessation and health questionnaire, saliva thiocyanate testing.\n At 12-month follow-up, a nurse-client interaction was more effective than written self-help materials; however, smoking cessation rates were highest in the No Intervention control group, possibly related to having had coronary artery bypass graft surgery. Variables positively related to quitting were being male and married and having a higher income. With baseline factors considered, a quitter was most likely to be male and less than 48 years of age, have a high degree of perceived threat relative to medical diagnosis, and be in the individual intervention group. Only partial support for the study hypotheses was found.", "Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England Veterans Affairs Medical Center. Telephone interviews were completed with 3,239 smokers, and 2,054 agreed to participate (64%). Participants were randomly assigned to one of four conditions: stage-matched manuals (MAN); NRT plus manuals (NRT + MAN); expert system plus NRT and manuals (EXP + NRT + MAN); and automated counseling plus NRT, manuals, and expert system (TEL + EXP + NRT + MAN). Assessments were completed at baseline, 10, 20, and 30 months. The point prevalence cessation rates at final follow-up (30 months) were MAN, 20.3%; NRT + MAN, 19.3%; EXP + NRT + MAN, 17.6%; and TEL + EXP + NRT + MAN, 19.9%. Stage-matched manuals provided cessation rates comparable with previous studies. The addition of NRT, expert system interventions, and automated telephone counseling failed to produce a further increase in intervention effectiveness.\n ((c) 2006 APA, all rights reserved).", "The authors develop and test a culturally sensitive, low-intensity smoking cessation intervention for low-socioeconomic African Americans. African American adult smokers were randomly assigned to receive either a multicomponent smoking cessation intervention comprising a printed guide, a video, and a telephone booster call or health education materials not directly addressing tobacco use. The results of the study were mixed. Although no significant effects were observed for the entire treatment cohort, the results of post hoc analyses suggest that culturally sensitive self-help smoking cessation materials plus a single phone contact can produce short-term cessation rates similar to those reported for majority populations. This conclusion should be tempered by the low completion rate for the booster call and several design limitations of the study.", "This prospective randomized study examined the impact of three tailored intervention approaches to increase quitting rates among African-American smokers who were clients of a community health center that serves primarily low-income and indigent persons. Smokers were randomized to one of three groups: (1) health care provider prompting intervention alone, (2) health care provider prompting intervention with tailored print communications, and (3) health care provider prompting intervention with tailored print communications and tailored telephone counseling. Among the 160 smokers who completed the study, 35 (21.8%) had quit smoking at follow-up. Smokers who received the provider prompting intervention with tailored print materials were more likely to report having quit than smokers who received the provider intervention alone (32.7% vs. 13.2%, p < 0.05). Smokers who received all three intervention components were not more likely to report having quit at follow-up than those who only received the provider intervention (19.2% vs. 13.2%). Smokers who at baseline were less educated, smoked less than half a pack of cigarettes per day, had a stronger desire to quit, felt more efficacious, and had thought about quitting were more likely to report having quit at follow-up. These results provide support for continued refinement of tailored communications to aid smoking cessation among African-American smokers.", "This study evaluated the effects of written feedback adapted to a self-help mail intervention. The efficacy of the standard mail intervention treatment was 37% at the end of treatment, 22% at the 3-month follow-up, 19% at the 6-month follow-up, and 13% at the 12-month follow-up. In contrast, the standard mail program combined with personalized written feedback resulted in an efficacy of 51% at the end of treatment, 37% at the 3-month follow-up, 32% at the 6-month follow-up, and 27% at the 12-month follow-up. Both groups were significantly different from the control group at the end of treatment (0%), at the 3-month follow-up (1%), and at the 6-month follow-up (1%). There was a significant reduction in the number of cigarettes smoked daily among continuing smokers under both experimental conditions. The authors conclude that written feedback substantially increases abstinence rates when it is applied following similar guidelines to those used in clinical settings.", "Reaching nonvolunteer female smokers with effective smoking cessation programs is a critical public health challenge. Smokers (N = 2,786) among 15,004 female members of a health maintenance organization who completed a routine needs assessment were invited into the \"UCLA Preventive Health Behavior Study,\" consisting of five telephone interviews over 2 years assessing health practices. Participants (N = 1,396) were randomized into experimental or control conditions of an unsolicited, mailed, self-help smoking cessation program. Subjects were not alerted to the link between the program and the health study. Smoking status was assessed at 1, 6, 12, and 18 months. Across all subjects, point prevalence at 18 months was 18.62, and continuous abstinence was 2.71%. No difference was found between treatment and control groups regarding smoking status or readiness to stop smoking--raising questions about the value of mailing cessation materials to nonvolunteers. Quit rates increased over the 18-month follow-up; those still smoking at 18 months reported increased readiness to quit. Predictors at each follow-up point were examined multivariately.", "This study reports the outcome of a randomized controlled trial testing a computer-tailored smoking cessation intervention based on the transtheoretical model in a general population setting in Germany. Participants of the smoking intervention study were recruited from an existing general population health examination survey in a university hospital. The sample consisted of 611 current and former smokers at baseline, and of 485 participants in the core group of baseline daily cigarette smokers. Follow-ups were conducted 6, 12, 18, and 24 months after baseline. The intervention was designed for both current and former smokers, involved up to three individualized feedback letters, and was created using expert-system technology. Based on 7-day point-prevalence abstinence and 6-month prolonged abstinence as the outcome measures, the study identified no significant differences between the intervention and control groups. Modeling the full longitudinal data in generalized estimation equation analyses, using different nonresponse procedures, and adjusting for covariates did not alter the results. We conclude that the computer-tailored transtheoretical model-based smoking cessation intervention, as delivered in this study and in this special setting, was ineffective.", "Smokers aged 18 to 65 years (N = 1,044) who were able to quit for 24 hr were randomized using a 2 x 2 factorial design to compare nicotine gum to no gum use and self-help materials to no use of materials. All participants were offered a $100 incentive to quit and stay quit for 6 months. Six-month abstinence was 27% in the gum groups, compared with 19% in the no-gum group (p = .002). Compared with the no-gum group, relapse occurred at a significantly lower rate in the gum group for the entire 12 months of follow-up (odds of relapse in the gum group was 0.72, 95% confidence interval, 0.62 to 0.83). There was no significant main effect for the self-help materials, no interaction between gum and materials, and no evidence that the effectiveness of gum differed between the sexes or between heavy and light smokers. Nicotine gum is an effective adjunct to minimal-contact smoking cessation materials plus monetary incentive in a population-based sample of smokers.", "Three stage-based expert system interventions for smoking, high-fat diet, and unsafe sun exposure were evaluated in a sample of 2,460 parents of teenagers. Eighty-four percent of the eligible parents were enrolled in a 2-arm randomized control trial, with the treatment group receiving individualized feedback reports for each of their relevant behaviors at 0, 6, and 12 months as well as a multiple behavior manual. At 24 months, the expert system outperformed the comparison condition across all 3 risk behaviors, resulting in 22% of the participants in action or maintenance for smoking (vs. 16% for the comparison condition), 34% for diet (vs. 26%), and 30% for sun exposure (vs. 22%). Proactive, home-based, and stage-matched expert systems can produce significant multiple behavior changes in at-risk populations where the majority of participants are not prepared to change.\n ((c) 2004 APA, all rights reserved)", "nan", "One thousand two hundred thirty seven smokers responding to lung association announcements in five geographic areas were randomly assigned to one of four groups and mailed American Lung Association materials: 1) leaflets (L); 2) leaflets plus maintenance manual (L + M); 3) cessation manual (C); and 4) cessation and maintenance manuals (C + M). Five telephone interviews over one year achieved a 95 per cent follow-up completion rate. Nonrespondents as well as exclusive cigar and pipe users were classified as smokers. Twenty per cent quit initially, with 5 per cent continually abstinent in (C + M) at 12 months vs 2 per cent in (L) (p less than .05). Nonsmoking prevalence rates (no tobacco smoking in the past month), on the other hand, gradually increased after six months; at 12 months those with the maintenance component, (L + M) and (C + M), had higher rates (18 per cent) than (L) (12 per cent) or (C) (15 per cent). Leaflets and manual alone were least cost effective. Rising nonsmoking prevalence rates observed in all groups suggest that successful attempts to quit increased over time and that a contributing factor might have been the follow-up method. Although achieving lower quit rates than methods requiring attendance at a course, the self-help intervention has the advantages of greater availability, flexibility, and in some instances lower cost.", "This article presents results from an experimental study designed to evaluate the effects of two features of self-help smoking cessation booklets, format (i.e., day-by-day plan for quitting versus a less structured menu format) and quitting instructions (i.e., \"cold turkey\" versus gradual reduction) on smoking cessation. Four separate self-help booklets were developed for comparison in this study. Each varied on a combination of the two study factors, but were similar in content, length, style, and readability. The four booklets provided similar advice on how to quit smoking, emphasizing behavioral self-management principles. In addition to the experimental booklets, a fifth control booklet provided general information about smoking and its adverse effects, but no specific advice on quitting. Study subjects included 1,534 adult cigarette smokers who called a stop smoking hotline in Buffalo, New York seeking information on how to quit. Subjects were followed up by phone one month and six months after enrollment to assess changes in smoking behavior. Overall, 18% of subjects reported of being off cigarettes for at least one week at the time of the six month follow-up interview. The format of the booklet and quitting instructions had no effect on smoking cessation rates. In addition, the four booklets emphasizing behavioral self-management skills were no more effective than the control booklet (6 month non-smoking prevalence rate: 17% versus 19%). It is recommended that future self-help quit smoking booklets include information aimed at motivating cessation and focus less attention on teaching strategies for quitting.", "Self-help methods are preferred by smokers over clinic-based treatments providing more traditional services. Unfortunately, these more popular methods have not been extremely successful in getting smokers to quit. The poor success rates may be partially related to the lack of structure inherent in these treatment approaches. The present study examined a self-help program delivered to smokers via a written manual and limited duration phone calls--the latter to add structure to the treatment procedures. The results, a 23% abstinent rate, indicate that this approach has some promise for treating chronic smokers.", "To examine the options for use, efficiency, and effectiveness for structuring a population-based telephone smoking-cessation service.\n Callers (n=632) to a 1-800 number were randomized in a 2 (50-minute counseling with 2/6 calls) x 2 (pamphlet/booklet) design with print only control.\n Six-month use of the service was 0.6% of adult smokers. Service promotion cost 31.02 dollars/person. Telephone counseling resulted in higher continued abstinence (5%) than did print only (1%), P<.05. Amount of print and calls did not increase cessation. Six calls resulted in lower completion rates than 2 (22% vs 56%, P<.05).\n For planning, consider 1% use, low-cost promotion, pamphlet, 50-minute initial counseling plus 2 follow-ups, and minimize call-attempts.", "The purpose of the present study was to determine the effectiveness of a self-help smoking cessation manual for patients with pulmonary disease. All patients were advised to quit smoking by a respiratory specialist. Thirty-five patients were then provided with a manual detailing techniques for quitting; the remaining 40 patients served as a control and were given no additional information or instruction following advice. The cessation rate in the treatment group was 16.7%; and in the control group, 25.6%. This difference was not statistically significant. Approximately half of the patients who received the manual used it, and only 12.5% of the users found it helpful. It was concluded that providing patients with the specific instructions on quitting smoking as presented in the manual did not appear to be useful.", "The present study assessed the incremental effectiveness of behavioral self-help materials specifically written to accompany nicotine gum. Subjects (187 women and 117 men) were randomly assigned either behavioral self-help booklets or a factual information pamphlet. All subjects received prescriptions for Nicorette from study physicians. Contrary to prediction, subjects provided self-help booklets fared no better than did subjects provided comparison pamphlets. Overall abstinence levels were encouraging, however. Nicotine gum users were far more likely than nonusers to maintain abstinence through 6-month follow-up. Perhaps self-help materials could be improved by condensing and simplifying content and by adopting a more attractive multicolored pictorial format.", "nan", "nan", "Physician-delivered advice to stop smoking is effective, but time demands often reduce the number of smokers who receive assistance. We evaluated three nurse-assisted interventions designed to minimize physician burden and increase counseling in primary care settings.\n Randomized controlled trial with a 12-month follow-up.\n Internal medicine and family practice offices in a health maintenance organization.\n Smokers (n = 3161) who were patients of participating physicians or other medical care providers (n = 60).\n Medical care providers delivered a 30-second stop-smoking prompt to 2707 smokers and referred them to an on-site nurse smoking counselor. The nurse randomly provided a two-page pamphlet (advice control) or one of three nurse-assisted interventions: 1) self-quit training; 2) referral to a group cessation program; or 3) a combination of self-quit training and referral. Each nurse-delivered intervention included a 10-minute video, written materials, and a follow-up phone call.\n Physicians delivered brief advice to 86% of identified smokers during the 1-year program. The proportion of participants reporting abstinence after both 3 and 12 months of follow-up nearly doubled (P = 0.01) for the nurse-assisted self-quit (7.1%), group-referral (7.6%), and combination (6.9%) interventions, compared to brief physician advice alone (3.9%) (P < 0.05). Saliva cotinine tests confirmed these effects (P < 0.004), although quit rates were lower (3.4%, 4.7%, 4.3%, and 2.3%, respectively) because roughly one half of quitters chose not to provide a saliva sample and were counted as smokers.\n Involving nurses in counseling smokers reduces physician burden, makes counseling more likely, and significantly increases cessation rates compared with brief physician advice alone." ]

[ "18794427" ]

[ "Significant reduction in incidence of wound contamination by skin flora through use of microbial sealant." ]

[ "Application of skin sealant prior to incision reduces microbial contamination of the wound.\n Prospective, randomized, multicenter clinical trial.\n Six teaching hospitals.\n A total of 177 adult patients undergoing elective open inguinal hernia repair were randomized to either standard skin preparation with 10% povidone-iodine or skin preparation followed by cyanoacrylate-based liquid microbial sealant.\n Wound contamination was assessed during surgery by microbial sampling inside the wound at initiation of skin incision and prior to skin closure.\n The primary outcome measures were the safety and effectiveness of cyanoacrylate-based microbial sealant to reduce bacterial contamination during surgery. The secondary outcome measure was reduction of postoperative surgical site infections using microbial sealant.\n Demographics were similar. Patients treated with sealant were more likely to have no bacterial cells found in the wound than control participants (47% vs 31%; P = .04). Three patients developed surgical site infections; all were in the control group (P = .25). Independent factors that reduced wound contamination were use of microbial sealant (odds ratio, 0.45; confidence interval, 0.23-0.88; P = .02) and perioperative antibiotics (odds ratio, 0.24; confidence interval, 0.10-0.58; P = .001).\n Cyanoacrylate-based microbial sealant may be an important tool to reduce wound contamination and potentially prevent surgical site infections." ]

[ "9751346", "16107868", "16490019", "14501741", "11728676", "16294343", "5553582", "15311032", "14745745" ]

[ "Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy.", "Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function.", "Sexual counseling improved erectile rehabilitation after non-nerve-sparing radical retropubic prostatectomy or cystectomy--results of a randomized prospective study.", "Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.", "Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study.", "Pilot intervention to enhance sexual rehabilitation for couples after treatment for localized prostate carcinoma.", "Postirradiation vaginitis. An evaluation of prophylaxis with topical estrogen.", "Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial.", "The effect of dyadic intervention on self-efficacy, social support, and depression for men with prostate cancer." ]

[ "A retrospective analysis of the MUSE clinical trial was performed to evaluate the efficacy and safety of transurethral alprostadil in patients with erectile dysfunction after radical prostatectomy.\n Patients received doses of transurethral alprostadil in the clinic and those for whom a suitable dose was determined were treated at home with active drug or placebo for 3 months. Patients had undergone radical prostatectomy no less than 3 months before study entry.\n Of the 384 patients in whom radical prostatectomy was identified as a cause of erectile dysfunction 70.3% had an erection believed sufficient for intercourse in the clinic and 57.1% on active medication had sexual intercourse at least once at home. The product of clinic and home success rates (70.3 x 57.1%) was an overall success rate (the likelihood of active treatment to lead to intercourse at home) of 40.1%. The frequency of most adverse effects of radical prostatectomy was comparable to that of other organic etiologies of erectile dysfunction (1,127 patients). The percentage of patients with hypotension in the clinic was lower after radical prostatectomy compared to other erectile dysfunction etiologies (0.8 versus 4.2%, p < 0.001) but the percentage of patients with urethral pain/burning was higher (18.3 versus 10.4%, p = 0.027). No urinary tract infection, fibrosis or priapism occurred in the post-radical prostatectomy patients.\n Transurethral alprostadil is a well tolerated and efficacious method of treating erectile dysfunction after radical prostatectomy, although psychological changes associated with cancer and surgery may limit home response. The severe neurovascular deficit associated with prostatectomy neither limits the efficacy of transurethral alprostadil nor increases the risks.", "To assess the efficacy of vacuum constriction devices (VCD) following radical prostatectomy (RP) and determine whether early use of VCD facilitates early sexual activity and potentially earlier return of erectile function. This prospective study consisted of 109 patients who underwent nerve-sparing (NS) or non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed erectile dysfunction following surgery. The patients were randomized to VCD use daily for 9 months (Group 1, N=74) or observation without any erectogenic treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of Erectile Function (IIEF-5)), which were stratified by the NS status. Patient outcome regarding compliance, change in penile length, return of natural erection, and ability for vaginal intercourse were also assessed. The mean patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully used their VCD with a constriction ring for vaginal intercourse at a frequency of twice/week with an overall spousal satisfaction rate of 55% (33/60). In all, 19 of these 60 patients (32%) reported return of natural erections at 9 months, with 10/60 (17%) having erections sufficient for vaginal intercourse. The abridged IIEF-5 score significantly increased after VCD use in both the NS and NNS groups. After a mean use of 3 months, 14/74 (18%) discontinued treatment. In Group 2, 37% (13/35) of patients regained spontaneous erections at a minimum follow-up of 9 months after surgery. However, only four of these patients (29%) had erections sufficient for successful vaginal intercourse and rest of patients (71%) sought adjuvant treatment. Of the 60 successful users, 14 (23%) reported a decrease in penile length and circumference at 9 months (range, 4-8 months) compared to 12/14 (85%) among the nonresponders. However, in control group 22/35 reported decrease in penile length and circumference. Early use of VCD following RP facilitates early sexual intercourse, early patient/spousal sexual satisfaction, and potentially an earlier return of natural erections sufficient for vaginal penetration.", "The efficacy of prostaglandin E1 (PGE1)-intracavernous injection (ICI) therapy for erectile dysfunction (ED) after non-nerve-sparing (NNS) radical pelvic surgery depends on patient compliance. The purpose of this study was to verify the utility of sexual counseling in ICI in terms of treatment efficacy, compliance, and dropout rate.\n In this prospective randomized study, 57 patients with ED after NNS radical prostatectomy or cystectomy were divided: 29 patients (group SC+) were treated with sexual counseling and PGE1-ICI therapy; the others 28 (group SC-) were treated with only ICI. At the start of the study all patients were administered the International Index of Erectile Function (IIEF) questionnaire and ICI training test; follow-up (at 3, 6, 9, 12, 18 months) was achieved by home Sildenafil test and ambulatory IIEF test; sexual counseling was provided only to group SC+.\n The mean IIEF score at the end of study was 26.5 (SC+) vs. 24.3 (SC-) (P < 0.05); eight patients (SC+, 27.5%) became responders to home Sildenafil vs. five (SC-, 17.8%) (P < 0.05); no dropout cases occurred (SC+) vs. eight (SC-, 28.5%) (P < 0.05). Moreover, we recorded best IIEF scores in group SC+ in sexual satisfaction (P < 0.05), sexual desire (P < 0.05), orgasmic function, and general satisfaction. Mean PGE1 doses were better in group SC+ (P < 0.05). ICI-oriented sexual counseling was utilized to motivate couples, to improve sexual intercourses, to correct mistakes in ICI administration. At the end of follow-up 21 patients (SC+) declared themselves satisfied vs. 12 (SC-).\n ICI-oriented sexual counseling in ICI increased the efficacy of treatment, the compliance, and Sildenafil responders rate, decreased the dropout rate.", "More than one-third of men may experience erectile dysfunction (ED) after nerve sparing radical retropubic prostatectomy. The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase 5 inhibitor, was assessed for the treatment of ED after radical prostatectomy.\n In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function, diary questions measuring vaginal penetration and intercourse success rates, and a global assessment question (GAQ) on erection.\n Of the intent to treat population 70% had severe ED (erectile function less than 11) at baseline. After 12 weeks both vardenafil doses were significantly superior to placebo (p <0.0001) for all efficacy variables. Improved erections (based on GAQ) were reported by 65.2% and 59.4% of patients on 20 and 10 mg vardenafil, respectively, and by only 12.5% of patients on placebo (p <0.0001). Among men with bilateral neurovascular bundle sparing, positive GAQ responses were reported by 71.1% and 59.7% of patients on 20 and 10 mg vardenafil, respectively, versus 11.5% of those on placebo (p <0.0001). The average intercourse success rate per patient receiving 20 mg vardenafil was 74% in men with mild to moderate ED and 28% in men with severe ED, compared to 49% and 4% for placebo, respectively. Few adverse events were observed. They were generally mild to moderate headache, flushing and rhinitis.\n In men with severe ED after nerve sparing radical retropubic prostatectomy, vardenafil significantly improved key indices of erectile function.", "To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer.\n 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded.\n Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate.\n Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.", "The majority of prostate carcinoma survivors experience enduring sexual difficulties and associated distress in the years after definitive treatment. A counseling intervention aimed at improving levels of sexual satisfaction and increasing successful utilization of medical treatment for erectile dysfunction (ED) was developed and pilot-tested for both the survivor of prostate carcinoma and his partner.\n All male participants were 3-month to 5-year survivors of localized prostate carcinoma who had been treated with radical prostatectomy or radiation therapy, and were married or in a committed relationship. Couples were randomized to attend four sessions of counseling together or to have the man attend alone. In both groups, partners completed behavioral homework. The sessions included education on prostate carcinoma and sexual function and options to treat ED as well as sexual communication and stimulation skills. Standardized questionnaires at baseline, posttreatment, and at 3-month and 6-month follow-up assessed sexual function, marital adjustment, psychologic distress, and utilization of treatments for ED.\n Fifty-one of 84 couples randomized to treatment completed the intervention (61%). Attendance by the partner did not affect outcomes. Participants completing the intervention demonstrated improvement in male overall distress (P < 0.01), male global sexual function (P < 0.0001), and female global sexual function (P < 0.05) at 3-month follow-up, but regression toward baseline was noted at 6-month follow-up. However, utilization of ED treatments increased from 31% at the time of study entry to 49% at the 6-month follow-up (P = 0.003).\n The results of this brief pilot counseling intervention demonstrated significant gains in sexual function and satisfaction and increased utilization of treatments for ED. However, modifications are needed in future randomized trials to reduce the rate of premature termination and to improve long-term maintenance of gains.\n Copyright 2005 American Cancer Society.", "nan", "We evaluated the efficacy and safety of tadalafil 20 mg, taken on demand, in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy (BNSRRP).\n This randomized, double-blind, placebo controlled multicenter study consisted of a 4-week treatment-free run-in period (baseline) followed by 12 weeks of treatment. A total of 303 men (mean age 60 years) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score, and the percentage of positive responses to Sexual Encounter Profile questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end points. We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence, defined as 50% or greater \"yes\" responses to Sexual Encounter Profile question 1 (ability to achieve at least some erection) during baseline intercourse attempts and stratified randomization based on this criterion.\n Patients receiving tadalafil reported greater improvement on all primary and secondary end points (p <0.001) compared to placebo. For all randomized patients and for the subgroup with evidence of postoperative tumescence, the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/- 0.5 and 5.9 +/- 0.7, respectively, p <0.001 vs placebo for both). For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. Of all patients randomized to tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported improved erections. Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%) were the most commonly reported adverse events.\n Tadalafil 20 mg, taken on-demand, was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP.", "Urinary and sexual dysfunctions are side effects of radical prostatectomy (RP) for prostate cancer (PC) that contribute to depression. Despite the effectiveness of support groups at reducing depression in cancer patients, men typically do not participate in them. The purpose of this pilot study was to test the effects of a dyadic intervention (one-to-one support) on social support (Modified Inventory of Socially Supportive Behaviors), self-efficacy (Stanford Inventory of Cancer Patient Adjustment), and depression (Geriatric Depression Scale). Subjects were randomized to group. Controls (N=15; Mage=59.7) received usual care. Experimentals were paired with long-term survivors (LTS) who had RP and who had treatment side effects in common. Experimentals (N=15; Mage=57.5) met with a LTS 8 times in 8 weeks to discuss concerns associated with survivorship. No significant differences were detected on social support, but after 4 weeks, significant differences were present on depression between controls and experimentals, however these differences were not seen at 8 weeks. After 8 weeks, there were also significant differences on self-efficacy between controls and experimentals. Weekly anecdotal data supported the feasibility and acceptance of the intervention that was a low cost strategy effective at reducing depression and increasing self-efficacy in men treated by RP. Future research directions and clinical application is presented.\n Copyright 2003 John Wiley & Sons, Ltd." ]

[ "16227328", "18585831", "3608590", "16297507", "3545418" ]

[ "Clinical efficacy of anti-pneumococcal vaccination in patients with COPD.", "Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease.", "Pneumococcal infection and immunologic response to pneumococcal vaccine in chronic obstructive pulmonary disease. A pilot study.", "Response to pneumococcal vaccine in chronic obstructive lung disease--the effect of ongoing, systemic steroid treatment.", "Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease." ]

[ "A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD).\n A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454).\n There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01).\n PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.", "To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.", "We assessed the importance of Streptococcus pneumoniae and immunologic response to 14-valent pneumococcal vaccine in a randomized (saline placebo or vaccine) double-blind pilot study involving 103 patients with chronic obstructive pulmonary disease (COPD). Antibody titers, the flora of the sputum, respiratory infections or pneumonias, and deaths were monitored. The patients' antibody titers before immunization were higher than healthy control subjects. Titers rose normally in those vaccinated but declined more rapidly. Differences between the group receiving placebo and vaccine were not significant at 12 and 24 months. The incidence of pneumonia was high before and after vaccine (47/1,000 vs 41/1,000 patient-years). Nonpneumococcal causes predominated (73 percent of pneumonias; 83.4 percent of lethal pneumonias). Isolates from sputum were predominantly nonvaccine types (50 to 62.5 percent). Twenty-seven patients died; pneumonia occurred in six (one pneumococcal in a vaccinated patient) as a terminal complication of other diseases. Thus, although pneumonia occurred frequently in these patients with COPD and contributed to mortality in 22 percent (six) of the 27 deaths, the predominance of nonpneumococcal causes and the data on antibodies and sputum suggest that pneumococcal vaccine may not be as beneficial for patients with COPD as was hoped. More observations are needed.", "Forty-nine patients with chronic obstructive lung disease (COPD) were block-randomized in four groups to investigate, if different degrees of steroid-load influenced the effect of pneumococcal-vaccination on antibody level and clinical variables during 6 months of follow-up. The groups included 13 patients without systemic steroids for the previous 3 months, all vaccinated at entrance in the study and treated with steroids for 4 weeks. Nine patients had chronic steroid treatment both before and during the investigation; they were vaccinated at the entrance in the study. Fifteen patients without systemic steroids for the previous 3 months were vaccinated after the end of a 4-week steroid treatment. Twelve patients served as controls, and were not vaccinated. Totally, 60%-78% of vaccinated patients in the three groups had a rise in antibody level, and a later decrease compared to two of the 12 control patients (p<0.01). This difference was also significant (p<0.05) for the patients vaccinated at entrance in the hospital. No differences were observed among the clinical variables: pneumonia, exacerbations, admittance to hospital, increase in the use of steroids or beta-agonists, and the use of antibiotics. We conclude that a rise in antibody level after pneumococcal vaccination can be expected in patients with COPD despite of the use of systemic steroids. The clinical effect of vaccination is debatable.", "Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings." ]

[ "8876776", "19494439" ]

[ "Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's Disease Cooperative Study.", "Vitamin E paradox in Alzheimer's disease: it does not prevent loss of cognition and may even be detrimental." ]

[ "This report describes the rationale and design of a clinical trial using selegiline (10 mg/day) and alpha-tocopherol (2,000 IU/day) to slow the progression of dementia in Alzheimer disease (AD). This study was developed by the Alzheimer's Disease Cooperative Study (ADCS), a consortium of clinical research centers actively involved in AD research. The major goal of the consortium is to design and conduct clinical investigations leading to the development of treatments for AD. This study uses a randomized double-blind, placebo-controlled, 2 x 2 factorial, parallel group design to test two drugs for the treatment of AD. The primary outcome of the study is the time to reach any one of the following four endpoints: death, institutionalization, loss of two of three basic activities of daily living, and progression of Clinical Dementia Rating (CDR) stage from 2 to 3. Patients with moderately severe disease (CDR = 2) were enrolled and evaluated 10 times over a period of 2 years to determine if these agents reduce the time to reach any endpoint. A database from the Consortium to Establish a Registry for Alzheimer's Disease indicated adequate power analyses to observe a treatment effect on this clinically meaningful outcome measure. Recruitment and baseline characteristics of the population are provided. The rationale for the choice of a factorial design, the use of a novel, clinically meaningful endpoint, and the selection of a cohort of patients with AD of moderate severity are discussed.", "There is controversy as to whether vitamin E is beneficial in Alzheimer's disease (AD). In this study, we tested if vitamin E prevents oxidative stress and loss of cognition in AD. Fifty-seven AD patients were recruited and divided in two groups: placebo or treated with 800 IU of vitamin E per day for six months. Of these 57 patients, only 33 finished the study. We measured blood oxidized glutathione (GSSG) and used the following cognitive tests: Mini-Mental State Examination, Blessed-Dementia Scale, and Clock Drawing Test. Of those patients treated with vitamin E, we found two groups. In the first group, \"respondents\" to vitamin E, GSSG levels were lower after the treatment and scores on the cognitive tests were maintained. The second group, \"non-respondents\", consisted of patients in which vitamin E was not effective in preventing oxidative stress. In these patients, cognition decreased sharply, to levels even lower than those of patients taking placebo. Based on our findings, it appears that vitamin E lowers oxidative stress in some AD patients and maintains cognitive status, however, in those in which vitamin E does not prevent oxidative stress, it is detrimental in terms of cognition. Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient." ]

[ "2060165", "9476272", "1954640", "9433873", "8810671" ]

[ "Tipi. A popular analgesic tea: a double-blind cross-over trial in osteoarthritis.", "Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip. A prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial.", "Treatment of arthritis with topical capsaicin: a double-blind trial.", "Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect.", "Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double-blind study." ]

[ "nan", "One of the objectives of symptomatic slow-acting drugs for osteoarthritis is to reduce the need for drugs with a less favorable safety profile, mainly analgesics and nonsteroidal antiinflammatory drugs (NSAIDs). We conducted a three-month, prospective, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of avocado/soybean unsaponifiables in terms of NSAID use reduction. Patients with primary femorotibial or hip osteoarthritis (OA) (ACR criteria and Kellgren-Lawrence radiological stage IB, II, or III) of at least six months' duration with regular pain for more than three months requiring therapy with NSAID (visual analog scale score > or = 25 mm and Lequesne's index on therapy > or = 4) were given one capsule per day of avocado/soybean unsaponifiables or a placebo for three months. During the first 45 days, patients in both groups were also given one of seven predefined NSAIDs. The primary efficacy criteria was the rate of patients taking back a NSAID and the delay before re-intake. Secondary efficacy criteria were the total dose of NSAID, overall ratings by the patient and by the physician, the visual analog scale pain score and the functional index. Of the 164 included patients, 163 were evaluable, 80 in the active drug group and 83 in the placebo group. Mean age was 62.9 +/- 8.8 years. The diagnosis was femorotibial OA in 101 patients and hip OA in 62. Data were collected on day 45 in 153 patients (77 on the active drug and 76 on the placebo). The number of patients who took back NSAID therapy was significantly smaller in the group treated by avocado/soybean unsaponifiables (33; 43.4%) than in the placebo group (53; 69.7%) (P < 0.001). Also, beyond day 54, the time spent off NSAID therapy was shorter in the placebo group. The functional index showed a significantly greater improvement in the active drug group (-2.3 +/- 2.6) than in the placebo group (-1.0 +/- 2.6) (P < 0.01). Pain scores over time were similar in the two groups. Overall patient ratings were significantly better in the active drug group (P < 0.01). Safety was oggd in both groups. After six weeks, avocado/soybean unsaponifiables reduced the need for NSAID in patients with lower limb OA.", "The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. In this double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily. Pain relief was assessed using visual analog scales for pain and relief, a categorical pain scale, and physicians' global evaluations. Most of the patients continued to receive concomitant arthritis medications. Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study; after four weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57% and 33%, respectively. These reductions in pain were statistically significant compared with those reported with placebo (P = 0.003 and P = 0.033, respectively). According to the global evaluations, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment. Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients; two patients withdrew from treatment because of this side effect. It is concluded that capsaicin cream is a safe and effective treatment for arthritis.", "To assess the efficacy and safety of avocado/soybean unsaponifiables (ASU) in the treatment of patients with symptomatic osteoarthritis (OA) of the knee or hip, as well as the potential residual effects of ASU after stopping treatment, to determine whether ASU might be a symptomatic slow-acting drug for the treatment of OA.\n One hundred sixty-four patients with regular, painful, primary OA of the knee (n = 114) or hip (n = 50) entered a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial with a 6-month treatment period and a 2-month posttreatment followup. A 15-day washout period for nonsteroidal antiinflammatory drugs (NSAIDs) preceded the study. Efficacy was judged according to 1) Lequesne's functional index (LFI) and 2) pain on Huskisson's visual analog scale (VAS; 100-mm scale), intake of NSAIDs/analgesics, and overall disability score (by 100-mm VAS).\n Eighty-five patients received ASU; 79 received placebo. One hundred forty-four patients were evaluable at month 6 (75 taking ASU; 69 taking placebo). The mean +/- SEM LFI score decreased from 9.7 +/- 0.3 to 6.8 +/- 0.4 in the ASU group and from 9.4 +/- 0.3 to 8.9 +/- 0.4 in the placebo group (P < 0.001 for intergroup difference at month 6). Pain decreased from 56.1 +/- 1.6 mm to 35.3 +/- 2.3 in the ASU group and from 56.1 +/- 1.8 mm to 45.7 +/- 2.6 in the placebo group (P = 0.003 at month 6). NSAID consumption was slightly lower in the ASU group. Fewer patients in the ASU group required NSAIDs (48%, versus 63% in the placebo group; P = 0.054). The success rate was 39% in the ASU group and 18% in the placebo group. Overall functional disability was significantly reduced in the ASU group. Improvement appeared more marked in patients with hip OA. A residual effect was observed at month 8. Tolerance was good to excellent for most patients.\n ASU treatment showed significant symptomatic efficacy over placebo in the treatment of OA, acting from month 2 and showing a persistent effect after the end of treatment.", "Eighty-two subjects with chronic arthritic pain were randomly assigned for 2 months without cross-over to either Reumalex, a licenced over-the-counter (OTC) herbal medicine, or a placebo. Entry characteristics were determined by a previous survey of arthritic customers at pharmacy and healthfood shop outlets. The AIMS2 questionnaire was completed at monthly intervals throughout and for 2 months prior to the trial, and a modified Ritchie Index provided clinical scores. Subjects also completed diary recordings of their use of self-prescribed analgesics and events they considered significant. There was a small but statistically significant improvement in pain symptoms, less so in sufferers from osteoarthritis. There were no other significant changes in any other measures nor in the use of other self-prescribed analgesics. There were few side-effects noted. It is concluded that Reumalex has a mild analgesic effect in chronic arthritis at a level appropriate to self-medication." ]

[ "14997954", "8063980", "1383947", "2886403", "4031216", "2738212", "8113478", "11000645" ]

[ "Cognitive therapy for depression: a comparison of individual psychotherapy and bibliotherapy for depressed older adults.", "Comparative effects of cognitive-behavioral and brief psychodynamic psychotherapies for depressed family caregivers.", "Effects of group interventions on cognition and depression in nursing home residents.", "Bibliotherapy for depressed older adults: a self-help alternative.", "Solicitation of elderly depressives for treatment outcome research: a comparison of referral sources.", "Comparative efficacy of cognitive and behavioral bibliotherapy for mildly and moderately depressed older adults.", "Comparative effectiveness of social problem-solving therapy and reminiscence therapy as treatments for depression in older adults.", "Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults." ]

[ "Thirty-one community-residing older adults age 60 or over either received 16 sessions of individual cognitive psychotherapy (Beck, Rush, Shaw, & Emery, 1979) or read Feeling Good (Bums, 1980) for bibliotherapy. Posttreatment comparisons with the delayed-treatment control indicated that both treatments were superior to a delayed-treatment control. Individual psychotherapy was superior to bibliotherapy at posttreatment on self-reported depression, but there were no differences on clinician-rated depression. Further, bibliotherapy participants continued to improve after posttreatment. and there were no differences between treatments at 3-month follow-up. Results suggest that bibliotherapy and that individual psychotherapy are both viable treatment options for depression in older adults.", "Clinically depressed family caregivers (N = 66) of frail, elderly relatives were randomly assigned to 20 sessions of either cognitive-behavioral (CB) or brief psychodynamic (PD) individual psychotherapy. At posttreatment, 71% of the caregivers were no longer clinically depressed according to research diagnostic criteria (RDC), with no differences found between the 2 outpatient treatments. The results suggested therapy specificity; there was an interaction between treatment modality and length of caregiving on symptom-oriented measures. Clients who had been caregivers for a shorter period showed improvement in the PD condition, whereas those who had been caregivers for at least 44 months improved with CB therapy. These findings suggest that patient-specific variables should be considered when choosing treatment for clinically depressed family caregivers.", "The effects of cognitive-behavioral group therapy, focused visual imagery group therapy, and education-discussion groups on cognition, depression, hopelessness, and dissatisfaction with life were studied among depressed nursing home residents. Seventy-six depressed subjects with mild to moderate cognitive decline participated in nurse-led 24-week protocols. Data were collected 4 weeks before the interventions, 8 and 20 weeks after treatment initiation, and 4 weeks after treatment termination. There were no significant changes in depression, hopelessness, or life satisfaction scores for any of the three conditions. Participants in the cognitive-behavioral and focused visual imagery groups showed a significant improvement beginning 8 weeks after treatment initiation on cognitive scores. These findings are encouraging indications that cognitive-behavioral and focused visual imagery group therapies may reduce cognitive impairment in depressed nursing home residents with mild to moderate cognitive decline.", "nan", "nan", "The efficacy of bibliotherapy for mildly and moderately depressed older adults was examined. Cognitive bibliotherapy and behavioral bibliotherapy were compared with a delayed-treatment control condition. Results indicate that the two experimental conditions were superior to the control condition, but that the cognitive and behavioral bibliotherapies were nondifferentially efficacious. Sixty-six percent of the subjects demonstrated clinically significant change. There were no specific effects associated with either the cognitive or the behavioral interventions. Treatment gains were maintained at 6-month follow-up. The implications of bibliotherapy for geriatric depression as an alternative or adjunct to traditional treatments are discussed.", "Compared the effects of 2 psychotherapies based on divergent conceptualizations of depression in later life. Seventy-five older adults diagnosed with major depressive disorder were assigned randomly to problem-solving therapy (PST), reminiscence therapy (RT), or a waiting-list control (WLC) condition. Participants in PST and RT were provided with 12 weekly sessions of group treatment. Dependent measures, taken at baseline, posttreatment, and 3-month follow-up, included self-report and observer-based assessments of depressive symptomatology. At posttreatment, both the PST and the RT conditions produced significant reductions in depressive symptoms, compared with the WLC group, and PST participants experienced significantly less depression than RT subjects. Moreover, a significantly greater proportion of participants in PST versus RT demonstrated sufficient positive change to warrant classification of their depression as improved or in remission at the posttreatment and follow-up evaluations.", "Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia.\n To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia.\n Randomized, placebo-controlled trial (November 1995-August 1998).\n Four geographically and clinically diverse primary care practices.\n A total of 415 primary care patients (mean age, 71 years) with minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed all study visits.\n Patients were randomly assigned to receive paroxetine (n = 137) or placebo (n = 140), starting at 10 mg/d and titrated to a maximum of 40 mg/d, or problem-solving treatment-primary care (PST-PC; n = 138). For the paroxetine and placebo groups, the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring; for the PST-PC group, visits were for psychotherapy.\n Depressive symptoms, by the 20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components.\n Paroxetine patients showed greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0. 07]; P =.004) symptom resolution than placebo patients. Patients treated with PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13]; P =.13), but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks (P =.01). For dysthymia, paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P =. 01) or intermediate (difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P =.03). Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo (P>/=.12 for low-, intermediate-, and high-functioning groups). For minor depression, both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning (difference vs placebo in mean [SE] change in SF-36 mental component scores, 4.7 [2.03] for those taking paroxetine; 4.7 [1.96] for the PST-PC treatment; P =.02 vs placebo).\n Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression. The benefits of PST-PC were smaller, had slower onset, and were more subject to site differences than those of paroxetine." ]

[ "20212061", "20639023", "3103764", "17179687", "12696778", "20943711", "18324952", "17113893", "11435843", "9863850", "19616802", "18678843", "14694457", "12614251", "19818077", "7484484" ]

[ "Comparison of intravaginal electrical stimulation and trospium hydrochloride in women with overactive bladder syndrome: a randomized controlled study.", "Combined behavioral and individualized drug therapy versus individualized drug therapy alone for urge urinary incontinence in women.", "Micturition and the mind: psychological factors in the aetiology and treatment of urinary symptoms in women.", "Effects of bladder training and/or tolterodine in female patients with overactive bladder syndrome: a prospective, randomized study.", "Neuromodulative treatment of overactive bladder--noninvasive tibial nerve stimulation.", "Comparison of different treatment protocols in the treatment of idiopathic detrusor overactivity: a randomized controlled trial.", "A comparison of the efficacy of darifenacin alone vs. darifenacin plus a Behavioural Modification Programme upon the symptoms of overactive bladder.", "Comparison of electric stimulation and oxybutynin chloride in management of overactive bladder with special reference to urinary urgency: a randomized placebo-controlled trial.", "A crossover randomized trial of transcutaneous electrical nerve stimulation and oxybutynin in patients with detrusor instability.", "Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial.", "Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial.", "Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial.", "Clinical efficacy of tolterodine with or without a simplified pelvic floor exercise regimen.", "Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.", "Efficacy of simplified bladder training in patients with overactive bladder receiving a solifenacin flexible-dose regimen: results from a randomized study.", "Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial." ]

[ "To compare the effects of trospium hydrochloride and electrical stimulation on urodynamic parameters, bladder diary, quality of life and psychological symptoms in female patients with overactive bladder syndrome.\n Prospective, randomized controlled trial.\n Department of Physical Medicine and Rehabilitation, University Hospital.\n Thirty-five patients were divided into either trospium chloride (Group 1) or intravaginal electrical stimulation therapy (Group 2).\n All patients were assessed at the beginning of the treatment, at weeks 6 (end of treatment), 10 and 18 according to urodynamic parameters, voiding diary parameters, severity of urgency (visual analogue scale, VAS), the Incontinence Impact Questionnaire Short Form (IIQ-7), and the Beck Depression Inventory.\n Statistically significant improvements were observed in both groups according to some urodynamic parameters, voiding diary parameters, VAS urgency severity, Incontinence Impact Questionnaire Short Form and Beck Depression Inventory scores at the end of the treatment (P<0.05). During the 18-week follow-up period, deteriorations were observed in many parameters in both groups although improvements in the frequency of urgency, the frequency of incontinence episodes, VAS urgency severity, and Beck Depression Inventory score in Group 2 persisted (P<0.05). Significant differences were not detected between groups at the end of the treatment or during the posttreatment follow-up controls (P>0.05).\n No difference was detected between trospium hydrochloride and intravaginal electrical stimulation in the treatment of female overactive bladder syndrome. Discontinuation of both treatments caused deterioration in most of the objective and subjective symptoms of overactive bladder syndrome.", "We tested whether individualized drug therapy enhanced with behavioral training would result in better outcomes than individualized drug therapy alone.\n Participants were community dwelling women with urge predominant incontinence. Using a randomized clinical trial design women were randomized to 8 weeks (4 visits) of drug therapy alone (32) or drug therapy plus behavioral training (32). Drug therapy was individually titrated, extended release oxybutynin with proactive management of side effects. Behavioral training included pelvic floor muscle training and urge suppression techniques. The primary outcome measure was reduction in frequency of incontinence episodes on bladder diary at 8 weeks (with followup at 6 and 12 months). Secondary outcomes included patient satisfaction, global perception of improvement, Urogenital Distress Inventory and Incontinence Impact Questionnaire.\n In intent to treat analysis frequency of incontinence was reduced a mean of 88.5% in the drug alone group and 78.3% in the combined therapy group (p = 0.16). Outcomes were not significantly different between the groups in the analysis of completers (91.5% vs 86.2%, p = 0.34), or in either analysis at 6 or 12 months. The groups also did not differ significantly on secondary outcomes at any point. Participants in the drug alone group tended to be taking higher doses of oxybutynin at 8 weeks but the final dose did not differ significantly between the groups. Based on a conditional power calculation the trial was stopped early for futility.\n When drug therapy is implemented with frequent individualized dose titration, daily bladder diaries and careful management of side effects, initiating concurrent behavioral training does not enhance outcomes for urge incontinence in women.\n Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "The mental state of 211 women attending a urodynamic clinic was assessed using questionnaires. Patients with genuine stress incontinence had scores comparable with other patients with longstanding physical complaints. Patients with sensory urgency were more anxious than those with genuine stress incontinence. Patients with detrusor instability were as anxious as patients with sensory urgency and in addition had higher scores on the hysteria scale. A subset of patients (roughly a quarter of the total) was identified, comprising members of all three diagnostic groups, for whom urinary symptoms rendered life intolerable. These patients were as anxious, depressed, and phobic as psychiatric inpatients, emphasising the serious psychological morbidity experienced by patients with urinary symptoms. Fifty patients with detrusor instability or sensory urgency entered a randomised trial comparing psychotherapy, bladder drill, and propantheline. The psychotherapy group significantly improved on measures of urgency, incontinence, and nocturia, though not on frequency. Bladder training was an effective treatment for frequency and patients became less anxious and depressed. There was a modest improvement in frequency of micturition in patients given propantheline. Frequency may be a learnt disorder which responds to the direct symptom oriented approach of bladder training. Patients with urgency and nocturia predominating might derive more benefit from psychotherapy.", "We compared the effects of bladder training and/or tolterodine as first line treatment in female patients with overactive bladder (OAB). One hundred and thirty-nine female patients with OAB were randomized to treatment with bladder training (BT), tolterodine (To, 2 mg twice daily) or both (Co) for 12 weeks. Treatment efficacy was measured by micturition diary, urgency scores and patients' subjective assessment of their bladder condition. Mean frequency and nocturia significantly decreased in all treatment groups, declining 25.9% and 56.1%, respectively, in the BT group; 30.2% and 65.4%, respectively, in the To group; and 33.5% and 66.3%, respectively in the Co group (p<0.05 for each). The decrease in frequency was significantly greater in the Co group than in the BT group (p<0.05). Mean urgency score decreased by 44.8%, 62.2% and 60.2% in the BT, To, and Co groups, respectively, and the improvement was significantly greater in the To and Co groups than in the BT group (p<0.05 for each). Although BT, To and their combination were all effective in controlling OAB symptoms, combination therapy was more effective than either method alone. Tolterodine alone may be instituted as a first-line therapy, but may be more effective when combined with bladder training.", "Conservative treatment of overactive bladder employes behavioral or invasive neuromodulatory inhibition of miction reflex and administration of anticholinergic drugs.\n The aim of this study was to use non-invasive stimulation of the tibial nerve with the intention to achieve desired therapeutic effects without iatrogenic nerve damage using a superficial electrostimulation.\n All patients suffered from overactive bladder (OAB) without bladder outlet obstruction. OAB was examined by the Behavioral urge score BUS (0.0--the best and 1.0--the worst score), the International prostate symptom score IPSS (0--the best and 35--the worst score) and the Incontinence quality of life questionnaire IQOL (0.0--the worst and 1.0--the best index). The patients were divided into 3 groups: Group I--patients with electrode attached behind the medial ankle of the left lower extremity. The intensity of stimulation corresponded to 70% of the maximum amplitude of response from musculus abductor hallucis. Frequency of stimulation was 1 Hz and duration of the square impulse was 0.1 ms. Surface stimulation lasted 30 minutes and was repeated once a week. Group II--patients were treated by oral oxybutynin 5 mg t.i.d. Group III--patients without treatment. The BUS, IPSS, and IQOL were repeated after the treatment.\n The study included 28 females of average age 54 year (range 45 to 63). Mean IPSS was 17 (range 12 to 21), mean index of quality of life IQOL was 30 (range 12 to 78) and mean BUS score was 0.68 (range 0.50 to 0.86). Group I with stimulation did achieve statistically significant changes following the treatment: decrease of mean IPSS from 17 +/- 3 points to 6 +/- 4 points after the treatment, increase in mean IQOL from 36 +/- 10 to 68 +/- 20 and decrease of mean BUS from 0.65 +/- 0.12 to 0.43 +/- 0.16. Group II had similar statistically significant differences after the treatment of OAB. Group III noted no changes in the complaints.\n Noninvasive stimulation had improved subjective symptom related to overactive bladder, had no adverse events and was well tolerated. (Fig. 1, Tab. 1, Ref. 18.).", "To investigate and compare the effectiveness of various treatment protocols for the treatment of women with idiopathic detrusor overactivity.\n Prospective, randomized controlled trial.\n Departments of Physiotherapy and Rehabilitation and Obstetrics and Gynaecology, Hacettepe University.\n Forty-six subjects were randomized to three groups.\n The first group received only pharmacotherapy, the second group received only physiotherapy and in the third group pharmacotherapy was combined with physiotherapy (combined therapy group).\n All patients were evaluated at the beginning and at the end of treatment. Assessment parameters were maximum cystometric capacity, electromyographic activity of pelvic floor muscles, voiding diary parameters, the amount of urine leakage and the quality of life score.\n The maximum cystometric capacity and the electromyographic activity of pelvic floor muscles increased significantly and the number of voids/day and incontinence episodes/day, and the amount of urine leakage reduced significantly (P < 0.05) in both physiotherapy and combined therapy groups while there was no significant difference in the pharmacotherapy group. After treatment, the number of voids/day increased by 0.3 ± 3.4 in the pharmacotherapy group (P > 0.05) and decreased by 5.1 ± 5.5 and 4.7 ± 5.6 in the physiotherapy and combined therapy groups, respectively (P < 0.05). Statistically significant improvements were observed in all groups according to the number of voids/night and the quality of life scores at the end of the treatment.\n The physiotherapy protocol we introduced in the present study with or without anticholinergic therapy has a substantial positive impact on the treatment of female patients with idiopathic detrusor overactivity.", "This study assessed the benefit of adding behavioural modification to darifenacin treatment for overactive bladder (OAB).\n The ABLE trial was a randomised, open-label, parallel-group, multicentre study of 12 weeks of darifenacin treatment [with voluntary up-titration from 7.5 mg once daily (qd) to 15 mg qd at week 2] alone or in combination with a Behavioural Modification Programme (BMP) for men and women with dry or wet OAB. Efficacy was assessed as the change in the number (per day) of micturitions (primary variable), urge urinary incontinence (UUI) episodes, urgency episodes, pads used and nocturnal voids. Health-related quality of life (HRQoL) was also evaluated. Tolerability and safety assessments included adverse events and the number of discontinuations.\n Of 592 patients screened, 395 were randomised, 190 to darifenacin alone and 205 to darifenacin + BMP. At baseline, the majority of subjects were dry (mean 2.8 and three UUI episodes per day in the darifenacin and darifenacin + BMP groups respectively). At study end, darifenacin alone and darifenacin + BMP both produced significant reductions from baseline in median numbers of micturitions, UUI episodes, urgency episodes and nocturnal voids (all p < 0.05), but not in the number of pads used. HRQoL also improved. There were no significant differences between treatment groups in efficacy or HRQoL variables.\n Darifenacin treatment provides a degree of normalisation of micturition variables and improvement in HRQoL that cannot be further enhanced by behavioural therapy of the type used in this study. Whether behavioural modification would add benefit over darifenacin treatment in patients with more pronounced incontinence problems remains to be determined.", "To compare the efficacy of electric stimulation (ES), oxybutynin, and placebo in managing the symptom complex of overactive bladder (OAB), particularly urgency.\n A randomized placebo-controlled trial was conducted for 68 patients with OAB, placing emphasis on urinary urgency. The interventions for the 12-week treatment period, conducted by the physiotherapist, who was unaware of the progress and outcome, included a vaginal ES program using biphasic symmetric, pulsed current with a 10-Hz frequency, 400-micros pulse width, 10/5 duty cycle, and varying intensity; and oxybutynin (2.5 mg) or placebo three times per day. Identical preintervention and postintervention assessments included the measurement of warning time, urodynamics, voiding diaries, and King's Health Questionnaire.\n Of the 68 women who completed this study, 24 were in the ES, 23 in the oxybutynin, and 21 in the placebo group. The between-group comparison showed that significant improvements in daily voided volume, pad count, number of urgency and nocturia episodes, and the domain 2 score and total score of the King's Health Questionnaire existed between the ES and the other groups (all P < or = 0.050). The changes in warning time, maximal voided volume, number of urgency episodes, and frequency were significantly improved between oxybutynin and placebo (all P < 0.013). Additionally, a comparison of the voided volume in uroflowmetry between the ES and placebo groups revealed a greater difference after treatment (P = 0.013). The reduction rate of OAB was 58.4% for the ES, 39.1% for the oxybutynin, and 9.5% for the placebo group (P = 0.036).\n ES had the greatest subjective outcome for OAB and was the most effective of the three treatments. Oxybutynin was more effective than placebo.", "Management of idiopathic detrusor instability is difficult in most patients mainly due to the lack of a complete understanding of the pathophysiology. Oxybutynin and transcutaneous electrical nerve stimulation have been used but to our knowledge no direct comparisons have been made.\n Patients with frequency, urgency, urge incontinence and proved detrusor instability were studied with urodynamics, quality of life instruments, and frequency and volume charts. Patients were randomized to transcutaneous electrical nerve stimulation or oxybutynin. After 6 weeks of treatment, they were reassessed and after a washout of 2 weeks, they were started on the second arm of treatment and reassessed 6 weeks later.\n A total of 13 male and 30 female patients were studied. Functional capacity had increased and number of voids daily had decreased significantly compared with before treatment in both arms (p <0.005). There were significant improvements in symptom specific quality of life measures but no changes were found on the global Short Form 36 (SF-36) quality of life questionnaire. The volume to first desire to void and first unstable contraction had increased significantly with oxybutynin but not with transcutaneous electrical nerve stimulation. Of 23 patients 7 were stabilized with treatment, including 2 with oxybutynin only, 2 with either nerve stimulation or oxybutynin and the remaining 3 with only nerve stimulation. Total bladder capacity did not change significantly with either treatment but patients noticed side effects more commonly with oxybutynin.\n Both treatments clearly improved subjective parameters. However, only oxybutynin showed significant improvements in objective urodynamic parameters. Transcutaneous electrical nerve stimulation can be used in patients who cannot take oxybutynin. Further studies are needed to show the long-term efficacy and cost analyses of nerve stimulation.", "Urinary incontinence is a common condition caused by many factors with several treatment options.\n To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women.\n Randomized placebo-controlled trial conducted from 1989 to 1995.\n University-based outpatient geriatric medicine clinic.\n A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia.\n Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition.\n Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment.\n For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% \"much better\" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups.\n Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.", "The Overactive Bladder Innovative Therapy trial was a randomized, multicenter, controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release tolterodine. The reduction in overactive bladder symptoms along with global response assessments was evaluated.\n A total of 100 adults with urinary frequency were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine. Voiding diaries and an overactive bladder questionnaire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency, urinary urge incontinence episodes, voids causing waking, volume voided, urgency episodes and quality of life indices. Global response assessments were completed by subjects and investigators after 12 weeks of therapy.\n The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5% reporting cure or improvement compared to 54.8% of subjects on tolterodine (p = 0.01). Assessments by investigators were similar but did not reach statistical significance (p = 0.05). After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency, urge urinary incontinence episodes, urge severity and nighttime voids, as well as for improvement in voided volume. There were no serious adverse events or device malfunctions.\n This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.", "Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy.\n To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy.\n 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006.\n 9 university-affiliated outpatient clinics.\n 307 women with urge-predominant incontinence.\n 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months.\n The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment.\n 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]).\n Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%.\n The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms.", "To investigate whether the combination of tolterodine plus (Tp) a simple pelvic floor muscle exercise (PFME) program would provide improved treatment benefits compared with tolterodine alone (Ta) in patients with symptoms of overactive bladder (OAB).\n After a 1-2 week run-in period, 480 patients with symptoms of urinary frequency (> or =8 micturitions/24 hr), urgency, and urge incontinence (> or =1 episode/24 hr), were randomized to receive tolterodine 2 mg bid with or without a simple PFME program for 24 weeks in this multinational study. Treatment efficacy was assessed by comparing the change from baseline in 3-day micturition diary recordings.\n After 24 weeks' treatment, in the Ta group the urgency episodes reduced from mean of 4.1 to 1.5 (83% reduction) while in the Tp group the urgency episodes reduced from 4.2 to 2.1 (78.7% reduction). Mean incontinence episodes per day decreased from 3.21 (standard deviation (SD) 3.4) to 0.95 (SD 1.9) in Ta group and from 3.44 (SD 3.4) to 1.25 (SD 2.7) in the Tp group. Similarly, the number of micturition/24 hr were significantly reduced, from 12.78 to 9.20 (27.3% reduction) in the Ta group and from 11.87 to 9.29 (23% reduction) in the Tp group. There was an improvement in the patients' perception of urinary symptoms in 85.9% of patients on Ta and 81.7% patients on Tp PFME. There were no statistically significant differences between the groups with regard to any of the outcome parameters.\n Tolterodine therapy for 24 weeks results in significant improvement in urgency, frequency, and incontinence, however, no additional benefit was demonstrated for a simple PFME program.\n Copyright 2003 Wiley-Liss, Inc.", "To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder.\n In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined.\n In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth.\n Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.", "To compare the efficacy of flexible-dose solifenacin 5/10 mg with and without simplified bladder training in patients with overactive bladder (OAB) syndrome.\n SOLAR (SOLifenacin Alone and with simplified bladder Re-training) was a multicentre, prospective, randomized, parallel-group, open-label study in patients with OAB. After a 2-week, single-blind, placebo run-in, 643 patients were randomized to treatment with either solifenacin 5 mg once daily (od) alone (323) or 5 mg od combined with simplified bladder training (320) for 8 weeks. At week 8, patients in both groups could request a dose increase to solifenacin 10 mg od for the remaining 8 weeks of the study. The primary efficacy endpoint was the change from baseline in the mean number of micturitions/24 h after 8 weeks. Secondary efficacy measures were the change in micturition frequency and other voiding diary variables at week 16. Patient-reported outcomes were also assessed, including patient Perception of Bladder Condition, Incontinence Quality of Life, and Treatment Satisfaction using a visual analogue scale score; tolerability was also assessed.\n Solifenacin given alone was effective in improving all measures of OAB evaluated in the study. When simplified bladder training was used combined with solifenacin there was a further significant improvement in micturition frequency at week 8, and this difference was maintained through to week 16. The use of simplified bladder training with solifenacin also significantly improved treatment satisfaction at week 16 over the responses to solifenacin given alone. There was no significant difference between the treatment groups at week 16 in urgency, incontinence or other secondary variables measured. The most common adverse event reported was dry mouth in both treatment groups; there was a low rate of discontinuation due to adverse events in the total study group.\n Combined treatment with solifenacin and simplified bladder training was more effective than solifenacin alone in reducing micturition frequency at weeks 8 and 16, and improving treatment satisfaction at week 16 in patients with OAB. Simplified bladder training did not improve on the benefits of solifenacin alone in the symptoms of urgency or incontinence.\n © 2009 THE AUTHORS. JOURNAL COMPILATION © 2009 BJU INTERNATIONAL.", "The aim of this study was to examine the efficacy of oxybutynin plus bladder training in the treatment of detrusor instability in frail elderly patients living independently in the community. It was a randomized, double-blind, placebo-controlled parallel-group trial of oxybutynin in 57 elderly patients (mean age 82.2, SD 6.06), with frequency and incontinence due to detrusor instability. After a 2-week run-in period patients received a bladder training and drug or placebo for the next 6 weeks. Outcome measures were changes in frequency and incontinence, recorded throughout on diary charts, and subjective evaluation of symptoms ('better'/'not better', and using a four-point scale 'cure' to 'no change'). Oxybutynin was superior to placebo in reducing daytime frequency [95% confidence interval (CI) of difference in change in frequencies totalled over 14 days was -27.0, -6.0; p = 0.003] and in producing subjective benefit (at day 29 only), when 24/28 (86%) patients on oxybutynin described benefit compared with 16/29 (55%) on placebo (p = 0.02). There was no difference between the groups in reduction of incontinent episodes. The median dose of oxybutynin titrated for therapeutic effect was 5 mg/day, and for placebo 10 mg/day (CI of difference 0.001, 5.001; p = 0.05). Side-effects reported were of similar frequency (50%) in the two groups. We conclude that oxybutynin with bladder training is superior to bladder training alone in reducing frequency due to detrusor instability in very elderly people living at home." ]

[ "20103449", "18082856", "15105064" ]

[ "Intrauterine contraception for adolescents aged 14-18 years: a multicenter randomized pilot study of levonorgestrel-releasing intrauterine system compared to the Copper T 380A.", "Adolescent and young women's experience with the vaginal ring and oral contraceptive pills.", "Clinical performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women: a comparative study." ]

[ "Intrauterine contraception can provide adolescents with effective, long-term contraception as well as with other health benefits. In adult populations, intrauterine contraception rates highly in patient satisfaction and safety. It is rarely prescribed to adolescents because of limited data.\n Multicenter, randomized, controlled, participant-blinded pilot study of 14-18-year-old females assigned to the Copper T 380A intrauterine device or the Levonorgestrel Intrauterine System. Participants were followed up for 6 months following insertion.\n We enrolled 23 participants; 12 received the Levonorgestrel Intrauterine System, and 11 received the Copper T 380A. At 6 months, the continuation rates were 75% for the Levonorgestrel Intrauterine System users and 45% for the Copper T 380A users (p=.15). Two Copper T 380A users experienced partial expulsion. Heavy bleeding and pelvic pain were the most commonly reported side effects. Participants rated both methods favorably.\n This study shows that at 6 months, though not statistically significant, adolescent continuation rates trended towards being greater with the Levonorgestrel Intrauterine System compared to the Copper T 380A. These pilot data will be helpful in the design of a larger trial of intrauterine contraception use among adolescents.", "To compare acceptability of the vaginal contraceptive ring to that of oral contraceptive pills.\n Randomized, cross-over, 6-month study.\n Urban family planning clinic for young low-income patients.\n Sexually active females aged 15-21 years (n = 130).\n Participants were randomly assigned to use the vaginal ring or oral contraceptive pills for an initial study interval of three 28-day cycles, followed by three cycles of the alternate method.\n Participants completed surveys about method use, acceptability, and side effects at baseline, after three cycles, and after six cycles. We analyzed study data using ANOVA models for cross-over designs.\n We did not detect higher compliance with the ring as compared to oral contraceptive pills (P = 0.176), although overall approval of the ring was significantly higher on several items measured, including liked using method (P = 0.015), would recommend it to friends (P = 0.012), and not as hard to remember to use method correctly (P < or = 0.000). Participants were less worried about health risks while using the ring (P = 0.006), but reported that the ring was more likely to interfere with sex than the pill (P < or = 0.001) and that sex partners liked the pill (P = 0.034). Most women did not report bothersome side effects with either method.\n Adolescent and young women showed favorable acceptability of the vaginal contraceptive ring compared to oral contraceptive pills.", "This 1-year randomized study was carried out at family-planning clinics of two university hospitals to compare the safety and acceptability of a levonorgestrel-releasing intrauterine system (LNG IUS) and oral contraceptives (OCs) in young nulliparous women. The study population consisted of 200 women aged 18-25 years seeking contraception. Ninety-four women entered the LNG IUS group and 99 entered the OC group. Continuation rates, reasons leading to discontinuation, adverse events, menstrual questionnaires, subjective well-being and sexual behavior were evaluated. Nineteen women (20%) in the LNG IUS group discontinued the study during the 1-year observation period, and 27 discontinued (27%) in the OC group. The most common reason (31%) for discontinuation in the IUS group was pain. In the OC group, hormonal side effects were the predominant medical reason for study termination. The safety and acceptability of the LNG IUS for contraception was observed to be as good as with OCs, with a high continuation rate." ]

[ "5810448", "13690207", "3567124", "15198753", "6835891", "5458775", "2797637", "7651658", "11424777", "12834936", "3631470", "359109", "378732", "3826577", "14130015", "5153810", "7015539", "7943116", "10674503", "5458774", "6768376", "7041955", "3516202", "10549964", "15321621", "4564230", "2892742", "1609533", "13520837", "15601268", "7390376", "3331863", "19281581", "4907758", "3992403", "3812947", "15851889", "4913784", "634895", "5554332", "6110584", "16868406", "20008859", "1869004" ]

[ "Comparison of pentazocine and pethidine in normal labor.", "Analgesia during labor: a comparison of pentobarbital, meperidine, and morphine.", "A comparison of the effects of maternally administered meptazinol and pethidine on neonatal acid-base status.", "A double blinded randomised placebo-controlled study of intramuscular pethidine for pain relief in the first stage of labour.", "Preliminary clinical and pharmacokinetic experiences in the newborn when meptazinol is compared with pethidine as an obstetric analgesic.", "A comparison of the effects of pentazocine and pethidine administered during labour.", "Randomized comparison of meperidine and fentanyl during labor.", "Comparison of the effects of meperidine and nalbuphine on intrapartum fetal heart rate tracings.", "[Evaluation of the peripartum effects of 2 analgesics: meperidine and tramadol, used in labor].", "Pethidine versus tramadol for pain relief during labor.", "Nalbuphine for obstetric analgesia. A comparison of nalbuphine with pethidine for pain relief in labour when administered by patient-controlled analgesia (PCA).", "A double-blind comparison of butorphanol and meperidine in labour: maternal pain relief and effect on the newborn.", "Double-blind comparison of maternal analgesia and neonatal neurobehaviour following intravenous butorphanol and meperidine.", "Pethidine compared with meptazinol during labour. A prospective randomised double-blind study in 1100 patients.", "EVALUATION OF PHENAZOCINE WITH MEPERIDINE AS AN ANALGESIC AGENT DURING LABOR, BY THE DOUBLE BLIND METHOD.", "[Pethidine and pentazocine. A double-blind investigation in obstetric material].", "A comparison of meptazinol and pethidine for pain relief during the first stage of labour.", "Double-blind comparison of intravenous butorphanol (Stadol) and fentanyl (Sublimaze) for analgesia during labor.", "A comparison of patient-controlled analgesia fentanyl and alfentanil for labour analgesia.", "A comparison between pethidine and phenazocine (Narphen) for relief of pain in labour.", "Ventilatory depression of the newborn of women receiving pethidine or pentazocine. A double-blind comparative trial.", "Double-blind comparison of meptazinol and pethidine in labour.", "Comparative study of meptazinol and pethidine for the relief of pain in labour.", "Intramuscular opioids for maternal pain relief in labour: a randomised controlled trial comparing pethidine with diamorphine.", "A comparison of pethidine and remifentanil patient-controlled analgesia in labour.", "[Avacan versus Fortral. A controlled double blind investigation on parturient patients].", "Effect of some recent analgesics on labor pain and maternal and fetal blood gases and pH.", "[Effectiveness and tolerance of tramadol with or without an antiemetic and pethidine in obstetric analgesia].", "Meperidine hydrochloride and alphaprodine hydrochloride as obstetric Analgesic agents; a double-blind study.", "Patient controlled analgesia for labour: a comparison of remifentanil with pethidine.", "[Obstetrical analgesia with tramadol].", "[Obstetrical analgesia with tramadol--results of a prospective randomized comparative study with pethidine].", "A comparison of tramadol and pethidine analgesia on the duration of labour: a randomised clinical trial.", "Analgesia during labour: a comparison between dihydrocodeine and pethidine.", "Self-administered intravenous analgesia during labour. A comparison between pentazocine and pethidine.", "A double-blind comparison of intramuscular pethidine and nalbuphine in labour.", "Intravenous butorphanol, meperidine, and their combination relieve pain and distress in women in labor.", "Comparison of pentazocine and pethidine in labour.", "[Pain relief in childbirth; an analysis of the analgesic effects of transcutaneous nerve stimulation (TNS), pethidine and placebos (author's transl)].", "A comparison of the analgesics pentazocine and pethilorfan in the relief of pain during labour.", "Double-blind comparison of intravenously injected butorphanol and meperidine in parturients.", "A randomized, placebo-controlled trial of the effects of pethidine on labor pain, uterine contractions and infant Apgar score.", "Obstetric analgesia: a comparison of patient-controlled meperidine, remifentanil, and fentanyl in labour.", "[Pethidine or nalbuphine for obstetric analgesia?]." ]

[ "nan", "nan", "A randomized double-blind study compared the effects of equi-analgesic doses of maternally administered meptazinol (1.5 mg/kg) and pethidine (1.5 mg/kg) on neonatal acid-base status. Heel-prick samples were taken for assessment of acid-base status at 10 and 60 min after delivery. Maternal antenatal history, details of labour and neonatal status at delivery were also recorded. Meptazinol produced less neonatal respiratory depression than pethidine: the mean 10 min acid-base data from 16 infants whose mothers received pethidine were indicative of a respiratory acidosis (pH 7.13, SD 0.08, PCO2, 9.11, SD 2.2 kPa; standard bicarbonate 22.3, SD 3.1 mmol/l). This was not evident in the mean acid-base data from 16 infants whose mothers received meptazinol (pH 7.23, SD 0.07; PCO2 6.83, SD 1.6 kPa; standard bicarbonate 20.9, SD 4.2 mmol/l). The mean pH and PCO2 in the two treatment groups were significantly different (P less than 0.002) at 10 min but not at 60 min after delivery.", "It has recently been suggested that systemic pethidine is ineffective in relieving labour pain. This study aims to evaluate the analgesic efficacy of pethidine in labour.\n This is a double blinded randomised placebo-controlled study.\n Labour suite, Prince of Wales Hospital, Hong Kong. Population Fifty normal Chinese pregnant women in early labour.\n We planned to randomise 112 women in early labour to receive either intramuscular pethidine 100 mg or normal saline when they requested analgesia. An interim analysis was performed at sample size 50.\n The primary outcome assessed was the visual analogue scale (VAS) pain score after 30 minutes.\n The study was terminated after recruitment of the first 50 women when planned interim analysis showed a significantly greater reduction of VAS pain score in the pethidine group (P= 0.009). The median difference in VAS pain score between the two groups at 30 minutes was -17 [95% CI -30 to -4]. Mean time to first subsequent request for analgesia was greater in the pethidine group (232 minutes, 95% CI 135 to 329 minutes) compared with the control group (75 minutes, 95% CI 54 to 95 minutes). Eight women (32%) in the pethidine group needed no further analgesia vs one woman (4%) in the control group (P= 0.011). Women in the pethidine group gave greater scores for sedation and satisfaction. Neonatal outcome was similar.\n Systemic pethidine was more effective at relieving labour pain than placebo. Its analgesic effect, however, was modest.", "Preliminary results on the disposition of meptazinol in the neonate are reviewed. Meptazinol has a half-life of 3.4 hours compared with 22.7 hours for pethidine. In a randomised double blind trial of 100 patients the depressant effects in the newborn of meptazinol and pethidine were compared. There was no difference in the Apgar scores at 1 and 3 minutes. Weight loss and the incidence of neonatal jaundice were less when mothers received meptazinol although these differences did not reach statistical significance. However, the number of infants considered fit for discharge by the 6th day was significantly greater in the meptazinol groups. In 43 cases transcutaneous monitoring of arterial PO2 was carried out for 30 minutes following delivery. Although the mean PaO2 was similar for meptazinol and pethidine, significant variations in the PaO2 of 2.0 kPa or greater and significant neonatal activity as judged by episodes of crying and movement, were recorded in the meptazinol group. The results of the trial suggest that meptazinol may have less depressant effects on the newborn, and may be preferable to pethidine as an obstetric analgesic.", "nan", "This randomized investigation compared the efficacy of the conventional narcotic, meperidine, and a more potent and short-acting analgesic, fentanyl, during labor. One hundred five women with uncomplicated term pregnancies in active labor were randomly assigned to receive either intravenous fentanyl (50-100 micrograms every hour) or meperidine (25-50 mg every 2-3 hours) in a non-blinded manner. The analgesics were rated equivalent in efficacy. Maternal nausea, vomiting, and prolonged sedation occurred more frequently in the meperidine group. Naloxone use was significantly less in fentanyl- than in meperidine-exposed infants (one of 49 versus seven of 56; P less than .05). Neuroadaptive testing at approximately 2 hours and 24 hours postnatally revealed similar averaged scores in the two groups. Using the described intravenous dosing schedule, fentanyl was preferable to meperidine during labor because there was no prolonged maternal sedation or vomiting necessitating therapy and the requirement for neonatal naloxone was reduced.", "To examine the effects of meperidine and nalbuphine on intrapartum fetal heart rate (FHR) tracings using computer analysis.\n We studied 28 women with uncomplicated pregnancies in early labor at term with reactive FHR tracings. The women were randomized to receive either meperidine 50 mg or nalbuphine 10 mg intravenously on request. One-hour FHR recordings were obtained before and immediately after administration of the medications.\n There were no significant differences in the FHR characteristics of the two groups during the pre-treatment period. Nalbuphine significantly decreased the number of accelerations of 10 beats per minute (17 versus 4, P = .003) and 15 beats per minute (10 versus 1.5, P = .001), time spent in episodes of high variation (35.5 versus 10 minutes, P = .004), long-term variation (47 versus 29.8 milliseconds, P = .002), and short-term variation (8.4 versus 6.4 milliseconds, P = .03). Meperidine had no significant effect on any FHR characteristic.\n In the early intrapartum period of normal term pregnancies and at commonly used dosages, nalbuphine had a significant effect on FHR tracings, whereas meperidine had no effect, as determined by computer analysis.", "The need for analgesia to overcome pain in labour is highly requested by women today. Various ways either non pharmachologic e.g. Emotional sustain, psycho-prophylactic preparation, yoga and hypnosis or pharmachologic such as epidural blockade or parenteral are used. Therefore in our study we evaluated the efficacy and tolerability of the two opioids usually used today in parenteral analgesia to reduce pain during labour: Tramadol and Meperidine. We studied two groups of patients each made up of 20 women in labour, all at term and with a physiologic course of pregnancy. 75 mg i.m. of Meperidine chloryhydrate were somministered in the first group while in the second group 100 mg i.m. of tramadol chloryhydrate were somministered. Various maternal, fetal and neonatal parameters were then monitored demonstrating--A moderate maternal analgesic effect in both drugs (evaluated through the analogic grading of pain). In the group to whom Meperidine was given, sedative effects on the mother were observed associated with respiratory depression in the newborn (the latter evaluated through the Apgar index at 1st and 5th minute of life and pH of the blood obtained at the umbilical cord. The data obtained permitted us to conclude that Tramadol in accordance to the obtained in literature gives an analogous analgesic effect, with better tolerability for the absence of collateral effects on the mother, fetus and newborn.", "To evaluate and compare the analgesic efficacy and adverse effects of tramadol and pethidine in labor.\n Fifty-nine full term parturients were randomly assigned to one of two groups in active labor. Group 1 received 100 mg pethidine; group 2, 100 mg tramadol, intramuscularly. Analgesic efficacy, maternal side effects, changes in the blood pressure, heart rate, and duration of labor were assessed.\n At 30 and 60 min after drug administration, pain relief was greater in the pethidine group than in tramadol group. The incidence of nausea and fatigue was higher in the tramadol group. Following drug administration the decrease in systolic and diastolic blood pressure and the increase in heart rate were statistically significant in both groups. No significant difference was found between the groups when compared for duration of labor and Apgar scores. None of the neonates developed respiratory depression.\n Pethidine seems to be a better alternative than tramadol in obstetric analgesia because of its superiority in analgesic efficacy and low incidence of maternal side effects.", "A double-blind, randomised study of 60 patients who received intravenous increments of nalbuphine 3 mg or pethidine 15 mg by patient-controlled analgesia during the first stage of labour, was carried out. Pain intensity, sedation, uterine contractions, maternal cardioventilatory variables and fetal heart rate were recorded as well as any side effects. Apgar scores, time to sustained respiration and resuscitative measures required for the neonate were noted at delivery. Modified neonatal neurobehavioural studies and a retrospective assessment of maternal analgesia, satisfaction and tolerance were also carried out. Group mean values of pain scores of nalbuphine-medicated primiparous women were statistically significantly lower than those of pethidine-medicated patients (p less than 0.01). Other assessments did not demonstrate a statistical significance between the two groups.", "Butorphanol tartrate 1 mg and 2 mg were compared in 80 normal mothers at term in a double-blind study with meperidine hydrochloride 40 mg and 80 mg for the relief of pain in labour. Butorphanol was found to be as effective as meperidine in relieving pain in labour. The foetal condition, as measured by ECG monitoring, Apgar scores, time to sustained respiration, umbilical venous H+ (pH) and PCO2, and a general nursery survey were comparable for meperidine and butorphanol. No psychomimetic phenomena were seen. Assays indicated that both butorphanol and meperidine crossed the placenta. The mean concentration of butorphanol in neonatal serum was 0.84 times maternal serum at 1.5 to 3.5 hours after intramuscular administration of a single or two successive doses of butorphanol 1 mg or 2 mg to the mother. The mean concentrations for meperidine in neonatal serum was 0.89 times maternal serum at 0.85 to 3.6 hours after intramuscular administration of meperidine 40 mg or 80 mg to the mother. Neither analgesic caused severe depression of the infant except for one meperidine-treated case.", "Butorphanol (1 mg and 2 mg) and meperidine (40 mg and 80 mg), given intravenously, were evaluated for analgesic efficacy and safety in a double-blind randomized study employing 200 consenting pre-partum patients in moderate to severe pain during the late first stage of labour. Both drugs provided adequate relief of pain to the mothers. There was no significant difference in the rate of cervical dilation, the foetal heart rate, the Apgar score, pain relief or neonatal neurobehavioural scores betweeen those receiving butorphanol and those receiving meperidine. Twenty-two mothers who received butorphanol and eleven who received meperidine nursed their infants with no adverse effects observed. Side-effects were generally infrequent in this study; however, more side-effects were reported by the patients and observed by the investigator in the meperidine-treated cases (13%) than in the cases treated with butorphanol (2%).", "A randomised double-blind comparison of pethidine and meptazinol used as analgesics in labour was carried out in 1,100 consecutive women who would normally have received intramuscular pethidine. Pain assessments at 30-minute intervals were made independently by patients and midwives. Maternal and neonatal side effects were noted. The babies' requirements for resuscitation and weight changes in the first 5 days were studied. There was no difference in the analgesia provided by the two drugs; the pattern of side effects was similar, but the incidence of vomiting was greater following meptazinol administration. The babies in the two groups were similar with respect to resuscitation received, weight gains or losses and the incidence of clinical neonatal jaundice. The most striking findings were the poor quality of pain relief experienced by both groups following parenteral analgesics and the high incidence of side effects.", "nan", "nan", "Meptazinol and pethidine were compared in a double-blind randomized trial with regard to analgesia during the first stage of labour. It was concluded that neither drug is effective for sustained pain relief, and that there is no advantage of one over the other. However, neither drug affected maternal condition as reflected by respiratory rate, pulse rate and blood pressure, nor was any detrimental effect noted on the condition of the newborn infant. The critical reassessment of traditional drugs for analgesia in labour is suggested.", "Our purpose was to compare the analgesic properties, effect on labor, and maternal-fetal side effects of intravenous butorphanol and fentanyl.\n One hundred patients with uncomplicated term pregnancies were enrolled during early active labor. Each patient received standard doses of either fentanyl (50 to 100 micrograms) or butorphanol (1 to 2 mg) hourly on request in a double-blind manner. Pain was scored independently by the nurse and patient with a 10-point visual analog scale. Categoric and measurement data were collected for comparison of the effects on uterine activity, maternal and fetal well-being, and neonatal outcomes.\n The fentanyl (n = 50) and butorphanol (n = 50) groups were identical with respect to maternal age, race, parity, and weight. Greater improvement in pain relief was found after the first dose of butorphanol than after fentanyl (p < 0.05). When fentanyl was given, either more doses were necessary (3.2 +/- 1.3 vs 2.1 +/- 1.1, p < 0.01) or epidural analgesia was requested more often (16%, 32% vs 9%, 18%, p < 0.05). Uterine contraction patterns for the first hour after dosing were unchanged, and the duration of the first and second stages of labor were not different between the two groups. No differences in maternal or newborn adverse effects were observed.\n Both drugs were equally safe and without effect on active labor. Butorphanol provided better initial analgesia than fentanyl with fewer patient requests for more medication or epidural analgesia.", "To determine the analgesic efficacy of equipotent doses of PCA (patient-controlled analgesia) fentanyl and PCA alfentanil for labour pain.\n Twenty three, ASA I - II parturients between 32-42 wk gestational age in whom epidural analgesia was contraindicated were randomized to receive PCA fentanyl (Group F)or alfentanil (Group A). Plain numbered vials contained 21 ml fentanyl 50 microg x ml(-1) or alfentanil 500 microg x ml(-1). A one millilitre loading dose was administered. The PCA solution was prepared by diluting 10 ml study drug with 40 ml saline and the PCA pump was programmed to deliver a dose of 2 ml, delay of five minutes and a basal rate of 2 ml x hr(-1). Maternal measurements obtained were hourly drug dose, total dose, Visual Analog Pain Score (VAPS) q 30 min, sedation score q 1 hr and side effects. Neonates were assessed by 1,5, and 10-min Apgar scores, umbilical venous and arterial blood gases and neurobehavioural scores at four and 24 hr.\n Mean VAPS from 7 - 10 cm cervical dilatation were higher in Group A than in Group F (85.7+/-13.9 vs. 64.6+/-12.1; P<0.01) There were no inter-group differences in VAPS from 1-3 cm, or from 4-6 cm dilatation, in maternal sedation scores or side effects, or in neonatal outcomes.\n In the doses prescribed in this study, PCA fentanyl was found to provide more effective analgesia in late first stage labour than PCA alfentanil.", "nan", "Forty-two women at term received pethidine 100 mg and 43 received pentazocine 45 mg, both given in a double-blind randomized manner. There was no difference in analgesic effect between the groups, but twelve patients were judged to need more than one injection of pentazocine, compared with seven in the pethidine group. The Apgar scores at 1 and 5 min were significantly less in the pethidine group. Four neonates in the pethidine group and two in the pentazocine group were severely depressed and received naloxone between 5 and 15 min after birth. The remainder of the infants received naloxone 200 microgram i.m. 15 min after birth. From 5 min after birth, end-expiratory carbon dioxide concentrations and from 15 min transcutaneous PO2 were recorded. A significantly smaller end-tidal carbon dioxide concentration was measured when more than one injection of pentazocine had been given. Repeated doses of pethidine, on the other hand, resulted in a greater end-tidal carbon dioxide concentration. Vigorous ventilation was even more pronounced when naloxone was given indicating an analeptic effect when two drugs with antagonistic activity are combined. At no time was transcutaneous PO2 less than 6.1 kPa. We conclude that both pethidine and pentazocine produce adequate pain relief during labour, but more than one injection of pethidine is associated with greater neonatal depression.", "The analgesic efficacy and safety of intramuscular meptazinol and pethidine in the first stage of labour were compared in a randomized double-blind trial in 358 patients. Pain relief was measured on a verbal rating scale, maternal side effects were recorded and neonatal outcome assessed in the first 24 h. Pain relief during the first hour after injection was significantly greater in the meptazinol than in the pethidine group at 45 and 60 min. Thereafter, there was no difference between the treatments, and the duration of action was approximately the same. Twenty-eight per cent of patients experienced side effects after meptazinol compared with 35% after pethidine. The commonest were nausea and vomiting with a similar incidence in both groups. Most of the neonatal observations revealed no difference between the two drugs, but significantly more babies whose mothers had received meptazinol had an Apgar score of greater than or equal to 8 at 1 min after birth.", "A double-blind comparison of pethidine and meptazinol in the relief of pain during labour was undertaken in 205 healthy women. The protocol allowed 100 mg of the test drug to be repeated at intervals of 2 h to a maximum of three doses. It was noteworthy that only 29 mothers were given a second dose of narcotic. Every woman receiving one injection of meptazinol complained of moderate to severe pain after 2 h; 97% of those receiving one injection of pethidine were complaining of moderate to severe pain after 2 h. There was no difference between the two drugs with regard to pain relief or in side-effects both in mother and baby.", "To compare the pain relief and side effects of intramuscular pethidine with intramuscular diamorphine in labour.\n Double-blind randomised controlled trial.\n The labour ward in a UK teaching hospital.\n Sixty-nine nulliparous women and 64 multiparous women in labour who requested narcotic analgesia and remained undelivered one hour after trial entry.\n Nulliparous women were randomised to receive either 150 mg intramuscular pethidine or 7.5 mg intramuscular diamorphine. Multiparous women were randomised to receive either 100 mg intramuscular pethidine or 5 mg intramuscular diamorphine. All participants received the anti-emetic prochloroperazine at the same time as the trial drugs.\n Maternal analgesia assessed by a visual analogue score and verbal scales of pain intensity and pain relief, maternal sedation and vomiting, neonatal outcome assessed by Apgar scores and the need for resuscitation.\n More women allocated to receiving pethidine than to diamorphine reported slight or no pain relief at 60 minutes after administration of these drugs (P = 0.03). This trend was repeated in most of the other measures for maternal analgesia. There was no difference in maternal sedation, but the incidence of vomiting within 60 minutes was lower for women who received diamorphine (P = 0.02). Pethidine was associated with lower Apgar scores at 1 minute (P < 0.05).\n Intramuscular diamorphine in labour appears to have some benefits, compared with intramuscular pethidine, but the trial was small and further research, particularly into alternative opioids and long term effects on the infants is still needed.", "We conducted a double-blind randomised controlled trial comparing the efficacy of analgesia during labour of remifentanil and pethidine. Nine women were randomised to receive an i.v. bolus of remifentanil 0.5 microg.kg(-1)with a lockout period of 2 min and eight women were randomised to receive a bolus of pethidine 10 mg with a lockout period of 5 min. A visual analogue scale (VAS) scoring system was used to assess the level of pain hourly throughout the first and second stages of labour and a score was recorded within half an hour of delivery for the level of pain overall throughout labour (post delivery score). The study was terminated after 17 subjects, on agreement with the local ethics committee, due to concern with the poor Apgar scores in the pethidine group. With the data available, we demonstrated significantly lower mean hourly and post delivery VAS scores for pain in the remifentanil group (P < 0.05). The 1 and 5 min Apgar scores were significantly lower in the pethidine group compared with the remifentanil group (P < 0.05). This preliminary study suggests that remifentanil may have a use as patient-controlled analgesia for women in labour.", "nan", "This study attempts to determine the analgesic properties of nalbuphine, pentazocine and butorphanol during labor and their potential effects on maternal and fetal blood gases and pH. Butorphanol analgesia was superior to either nalbuphine or pentazocine in relieving labor pain. The studied analgesics caused significant maternal respiratory acidosis and fetal metabolic acidosis. These acidotic changes were most marked with pentazocine, moderate with nalbuphine and minimal with butorphanol.", "The aim of this prospective, randomised, blind study was to investigate the analgesic potency and tolerance of intramuscular Tramadol compared to a standard obstetric analgesia with Pethidine. Triflupromazine was administrated in combination with the two tested analgesics in order to study its efficacy in alleviating the emetic side effects of the tested analgesics. 66 parturients were randomly assigned to three groups: group A: 100 mg Tramadol (Tramal), group B: 100 mg Tramadol (Tramal) and 10 mg Triflupromazine (Psyquil), group C: 50 mg Pethidine (Alodan) and 10 mg Triflupromazine (Psyquil). No significant differences concerning duration of labour, FHR-alterations, umbilical cord blood gases, respiration pattern and Apgar Scores of the neonate occurred. In all three groups the analgesic effect was equally good. Combination of the analgesic with the antiemetic showed no reduction of the incidence and severity of side effects.", "nan", "We compared the analgesic efficacy and safety of remifentanil and pethidine via patient controlled analgesia for women in established uncomplicated labour. Women received either remifentanil 40 microg with a 2-min lockout (n = 20) or pethidine 15 mg with a 10-min lockout (n = 19). Visual analogue scores for pain during the study and for overall pain were similar for both groups (mean (SD) 6.4 (1.5) cm for remifentanil and 6.9 (1.7) cm for pethidine). The area under the curve for visual analogue scores of satisfaction with analgesia was higher for remifentanil than for pethidine (p = 0.001). Maternal arterial oxygen saturation was similar in both groups. Neurologic and Adaptive Capacity Scores at 30 min were higher for remifentanil than for pethidine (median (interquartile range [range]) 36 (34.5-37 [32-39]) vs 34 (33-35 [30-35]), respectively; p = 0.003).", "Parenteral analgesia with Tramal was performed in 23 normal deliveries. The results were compared with a group of normal deliveries in which analgesia was achieved with pethidine. Both medicaments excerted an identical analgetic efficiency. No adverse side effects were observed with Tramal concerning the follow-up of labour or the newborn. Tramal can be recommended for obstetrical analgesia since it does not excert inhibitory effects upon the respiratory center.", "Morphine derivatives are the most frequently used analgetic substances in obstetrics today. Nevertheless, nausea, vomiting, weariness, and somnolence are common side effects of these drugs. Moreover opiates exhibit a depressive effect on ventilatory activity. As many studies have demonstrated tramadol, a new analgetic substance amongst the opiates does not show a depressive effect to such a high degree. In this prospective randomized trial we compared the efficacy as well as the safety of 100 mg tramadol and 100 mg pethidine in 40 women asking for pain relief during labour. The duration of labour was slightly but not statistical significantly shorter in the pethidine group. An analgetic effect could be observed in the pethidine as well as the tramadol group by both the pregnant women and the attending physician about 10 min after application lasting for about 2 hours. Concerning the side effects tramadol highly contrasted with pethidine. There were less cases of weariness and somnolence and the ventilatory frequency of the newborn babies tended to be higher than in the pethidine group. The serum levels of tramadol in umbilical and maternal veins demonstrated values of 0.83 +/- 0.15 (mean +/- SEM; quotient). The results of this study seem to establish an analgetic effect of tramadol similar to pethidine but with less side effects.", "The ideal obstetric analgesia should provide analgesic efficacy without attenuation of uterine contractions.\n To compare the outcome of intramuscular administration of pethidine and tramadol in labour analgesia.\n One hundred and sixty full-term parturients were randomly assigned to two equal groups in active labour. Group P received 50 mg pethidine; and group T, 100 mg tramadol intramuscularly. Primary outcome measure was the duration of the labour. The analgesic efficacy, maternal side-effects, mode of delivery, maternal satisfaction and Apgar score as the secondary outcome were assessed.\n The duration of labour was shorter in group T, for first stage (190 vs 140 min; P < 0.0001) and for second stage (33 vs 25 min; P = 0.001). There were no differences in Groups P and T with respect to median (7 vs 8) and maximum (7.5 vs 8) visual analog scores (VAS) for pain at 10 min and one hour after drug administration. Women in group P had lower VAS pain scores than those in group T in the second stage of labour (8 vs 9; P = 0/009). There was a significantly higher incidence of nausea and vomiting (35% vs 15%; P = 0.003) and drowsiness (80% vs 29%; P < 0.0001) in group P.\n Both 100 mg tramadol and 50 mg pethidine provide moderate analgesia in first stage of labour. Tramadol seems to cause a shorter duration of labour and lower incidence of maternal side-effects. However, its analgesic efficacy was not found to be as effective as pethidine, especially in the second stage of labour.", "nan", "Pentazocine or pethidine was administered to healthy parturients up to the time of delivery using a self-demand (self-administration on demand) intravenous apparatus, the Cardiff Palliator. Good analgesia was obtained with both drugs. The patients receiving pethidine exhibited side-effects (nausea, vomiting and drowsiness), whereas there were no side-effects among those receiving pentazocine. Apgar and neurobehavioural scores of the babies of mothers in both groups were the same and did not differ from those of a third group of babies, the mothers of whom had received 4-hourly intramuscular pethidine on demand according to the usual hospital routine. The self-administration technique proved a safe and effective means of providing analgesia during labour and delivery, with pentazocine having a decided advantage over pethidine because of its lack of side-effects.", "A double-blind, between-patient comparison of intramuscular pethidine 100 mg and nalbuphine 20 mg for the relief of pain during labour in 80 patients is described. Severity of pain was assessed before and after treatment by subjective pain scores and visual analogue scales. Neither of these methods showed a significant difference between the treatments. Nalbuphine was associated with less maternal nausea and vomiting than pethidine, but this possible advantage was somewhat offset by a tendency of the drug to produce more maternal sedation and dizziness. The mean umbilical vein/maternal vein ratio was significantly higher for nalbuphine (0.78, SEM 0.03) than for pethidine (0.61, SEM 0.02), which suggests easier placental transfer of the former. This finding was reflected in significantly lower 2-4 hour neurobehavioural scores for the infants of mothers given nalbuphine, but there was no significant difference between these scores at 24 hours. On the basis of this study, nalbuphine does not offer a substantial improvement over pethidine for pain relief in labour.", "Systemic opioids are commonly administered during labor, but their efficacy has been recently questioned. In addition, laboratory and clinical studies provide a strong rationale for combining mu- and kappa-opioid receptor agonists for analgesia. The authors therefore studied, using validated intensity and affective scales and definitions of effective pain relief, the efficacy of intravenous meperidine, butorphanol, and their combination for labor analgesia.\n Healthy women with singleton term pregnancy requesting analgesia during active labor were studied. Women were randomly assigned to receive 50 mg meperidine, 1 mg butorphanol, or 25 mg meperidine plus 0.5 mg butorphanol (n = 15/group). Pain intensity was assessed using a 0-10 numerical rating scale, and affective magnitude was assessed using a ratiometric descriptive scale before drug administration and between the sixth and seventh uterine contractions after drug administration.\n All three treatments reduced pain intensity equally. Butorphanol alone did not reduce pain affective magnitude, whereas the other treatments did. There was a significant correlation between reduction in pain intensity and affective magnitude in all groups, with greater reductions in affective magnitude than intensity. Overall, 29% of women exhibited clinically meaningful pain relief, with no difference among groups. Groups did not differ in incidence of opioid-induced adverse effects.\n These doses of meperidine and butorphanol do reduce pain intensity and affective magnitude, although a minority of patients achieve meaningful pain relief as defined in multiple patient populations, including laboring women. Combination of these drugs did not improve their therapeutic benefit.", "A double-blind between-patient study was carried out comparing pentazocine with pethidine in 94 women in labour. Similar analgesic and sedative effects were obtained with the two drugs, and Apgar scores were similar for babies of both drug groups. Fewer emetic sequelae were reported after pentazocine injections, though there was no statistically significant difference between the two drug groups in incidence of other side-effects.", "The analgesic affects of TNS, pethidine and placebos on labour pain were studied in 30 parturient women during the first stage of labour. 10 had TNS paravertebrally in the region of the afferent nerves at Th 10-Th 12; one group of 5 had unspecific (wrong) TNS; in another group of five no current was applied (placebo); five women were given 50 mg of pethidine intravenously; five patients acted as a control group. To assess the analgesic effects the women were asked to estimate the intensity of pain (grades 1-6) over a period of 70 minutes. There was no significant difference between the placebo, unspecific TNS and control groups as regarded the increase in pain during the test period. Patients who had received pethidine and those who had been given TNS at the site of the afferent nerves transmitting impulses from the uterus experienced considerable relief of pain. The differences were highly significant. The observations prove the genuine analgesic action of TNS. The use of this technique in obstetrics is discussed.", "nan", "One hundred women with moderate-to-very-severe prepartum pain participated in a double-blind study of intravenously injected butorphanol and meperidine that compared the analgesic properties, effect on the process of labor, condition of the newborn and the incidence of side effects associated with the two drugs. Cervical dilation, infant birth weight and Apgar scores were not significantly different between the test groups. The mean fetal heart rate for the butorphanol group was significantly faster than that of the meperidine group. Butorphanol provided significantly more analgesia than meperidine at 30 minutes and one hour after administration, based on pain intensity and pain relief scores. Some side effects, including sedation, dizziness, lightheadedness, nausea, vomiting and pain at the injection site, were reported for both drugs.", "nan", "To compare the analgesic efficacy of remifentanil with meperidine and fentanyl in a patient-controlled setting (patient-controlled analgesia, PCA).\n Parturients (n=159) were randomly assigned to receive remifentanil (n=52), meperidine (n=53), or fentanyl (n=54). Pain scores and an observer sedation scores were assessed hourly. Fetal outcome was evaluated with Apgar score, cord blood gas analysis and the Neurologic and Adaptive Capacity Score.\n Pain scores decreased in all groups, the decrease varying from mild to moderate, average pain scores remaining above 4.5 cm in all groups. Remifentanil PCA was associated with the greatest decrease in pain scores, but the difference was significant only at 1 h. Pain scores returned towards baseline over time; 3 h after the initiation of treatment, pain scores no longer differed significantly from baseline values in any of the groups. Significantly more parturients receiving meperidine crossed over to epidural analgesia. Overall satisfaction scores were higher with remifentanil, but remifentanil produced more sedation and itching. More periods of desaturation (Sa(o(2)) <95%) were observed during administration of remifentanil and fentanyl. There were no significant differences in fetal outcome between the three groups.\n The efficacy of meperidine, fentanyl, and remifentanil PCA for labour analgesia varied from mild to moderate. Remifentanil PCA provided better analgesia than meperidine and fentanyl PCA, but only during the first hour of treatment. In all groups, pain scores returned to pre-treatment values within 3 h after the initiation of treatment.", "Because of the risk of ventilatory depression, agonistic and partially agonistic/antagonistic opiates are well suited for providing pain relief in obstetrics. We compared two groups of 20 women each with pregnancy on term who received equipotent doses of nalbuphin (0.1 mg/kg) and pethidin (0.8 mg/kg) intramuscularly. We found a significantly longer (6h) and better analgesic effect in the nalbuphin group but also a significantly more pronounced sedation. Other side effects were fewer in this last-named group. There were no differences in the behaviour of the babies between both groups. We consider that because of the \"ceiling effect\" of ventilatory depression, nalbuphin may allow better analgesia without the risk of ventilatory depression of both mother and newborn." ]

[ "7787918", "17085009", "15840076", "17322014", "18074473", "11604980" ]

[ "Psychophysiologic responses of mechanically ventilated patients to music: a pilot study.", "[Effects of music therapy in intensive care unit without sedation in weaning patients versus non-ventilated patients].", "Music and its effect on the physiological responses and anxiety levels of patients receiving mechanical ventilation: a pilot study.", "Influence of music on the stress response in patients receiving mechanical ventilatory support: a pilot study.", "Overture for growth hormone: requiem for interleukin-6?", "Effects of music therapy on anxiety in ventilator-dependent patients." ]

[ "Although mechanically ventilated patients experience numerous stressors, they have not been included in music therapy stress reduction and relaxation studies.\n To examine selected psychophysiologic responses of mechanically ventilated patients to music.\n A two-group experimental design with pretest, posttest, and repeated measures was used. Twenty mechanically ventilated patients were randomized to a music-listening group or a nonmusic (headphones only) group. Physiologic dependent measures--heart rate and rhythm, respiratory rate, systolic and diastolic blood pressure, oxygen saturation, and airway pressure--were collected at timed intervals. Psychologic data were collected before and after intervention using the Profile of Mood States.\n Using repeated measures analysis of variance, results for heart rate and respiratory rate over time and over time between groups were significant. Between-group differences were significant for respiratory rate. Significant differences were found via t test for the music group's Profile of Mood States scores. No adverse cardiovascular responses were noted for either group.\n Data indicated that music listening decreased heart rate, respiratory rate, and Profile of Mood States scores, indicating relaxation and mood improvement.", "Music has been found to be an effective nonpharmacologic adjunct for managing anxiety and promoting relaxation in limited trials of critically ill patients. However, its effects have not been compared in intubated patients during weaning from mechanical ventilation with non-intubated patients spontaneously breathing.\n A cross-over randomized experimental design.\n Thirty patients were studied (intubated group n = 15, non-intubated group n = 15). Patients were randomized to receive either 20 minutes of uninterrupted rest or then 20 minutes of music therapy or the music therapy first and then the uninterrupted rest period. Patients selected a relaxing music of their choice from a selection including different types of music. Heart rate (HR), systolic blood pressure (SAP), respiratory rate (RR) and bispectral index (BIS score) were recorded each 5-min intervals throughout both periods (rest and music). Agitation/sedation state and pain were evaluated by the Richmond-Agitation-Sedation-Scale (RASS) and the Numerical-Rating-Scale (NRS) respectively, before and after each studied periods. Music have not been performed in five patients (5/35 = 14%).\n Music significantly decreased HR (88+/-15 vs 82+/-15, P<0.05), SAP (137+/-17 vs 128+/-14, P<0.05), RR (25+/-3 vs 22+/-4, P<0.05), BIS (94+/-5 vs 81+/-10, P<0.01), RASS (+0.1+/-0.7 vs -0.7+/-0.9, P<0.05) and NRS (4.4+/-1.7 vs 1.9+/-1.3, P<0.01) in both intubated and non-intubated groups whereas no significant change was observed during the rest period. The variations level studied parameters induced by music were comparable for the two groups.\n A single music therapy session was found to be effective for decreasing anxiety and promoting relaxation, as indicated by decreases in heart rate, blood pressure, BIS and respiratory rate over the intervention period in intubated patients during weaning phase.", "The aim of this study was to investigate the effects of music on the anxiety of patients on mechanical ventilation, as assessed by objective parameters and a subjective validated anxiety scale.\n Mechanical ventilation, although sometimes lifesaving, is often associated with levels of anxiety requiring sedatives, which has inevitable implications on costs and complications.\n A randomized controlled trial design.\n A total of 64 subjects was randomly assigned to undergo either 30 minutes of music intervention or a rest period. The subjects were asked to answer the Chinese State Trait Anxiety Inventory scale before and after the study period and physiological indices and resting behaviours were recorded before and after the study period in both groups. The subjects' satisfaction with music was also obtained after music intervention.\n The findings indicate that patients on mechanical ventilation that listened to a single 30-minute session of music appeared to show greater relaxation as manifested by a decrease in physiological indices and an increase in comfortable resting behaviours.\n Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety in mechanically ventilated patients.\n As indicated by the results of this study, music therapy can act as a simple and safe nursing intervention to allay anxiety and promote patient comfort. Interest and comments on music therapy provided as a relaxation technique should be elicited from both nurses and patients.", "Music is considered an ideal therapy for reducing stress in patients receiving mechanical ventilation. Previous studies of the effect of music on stress in such patients have focused solely on indirect markers of the stress response rather than on serum biomarkers.\n To explore the influence of music on serum biomarkers of the stress response in patients receiving ventilatory support.\n A convenience sample of 10 patients receiving mechanical ventilation was recruited from an 11-bed medical intensive care unit. Patients were randomly assigned to listen to music or to rest quietly for 60 minutes. Levels of corticotropin, cortisol, epinephrine, and norepinephrine were measured 4 times during the 60 minutes.\n The levels of the 4 biomarkers of the stress response did not differ significantly between patients who listened to music and patients who rested quietly, though the levels of corticotropin and cortisol showed interesting trends.\n Additional research is needed with a larger sample size to evaluate further the influence of music on biochemical markers of the stress response in patients receiving mechanical ventilatory support. In future studies, confounding factors such as endotracheal suctioning and administration of medications that influence the stress response should be controlled for.", "Music has been used for therapeutic purposes since the beginning of cultural history. However, despite numerous descriptions of beneficial effects, the precise mechanisms by which music may improve human well-being remain unclear.\n We conducted a randomized study in ten critically ill patients to identify mechanisms of music-induced relaxation using a special selection of slow movements of Mozart's piano sonatas. These sonatas were analyzed for compositional elements of relaxation. We measured circulatory variables, brain electrical activity, serum levels of stress hormones and cytokines, requirements for sedative drugs, and level of sedation before and at the end of a 1-hr therapeutic session.\n Compared with controls, we found that music application significantly reduced the amount of sedative drugs needed to achieve a comparable degree of sedation. Simultaneously, among those receiving the music intervention, plasma concentrations of growth hormone increased, whereas those of interleukin-6 and epinephrine decreased. The reduction in systemic stress hormone levels was associated with a significantly lower blood pressure and heart rate.\n Based on the effects of slow movements of Mozart's piano sonatas, we propose a neurohumoral pathway by which music might exert its sedative action. This model includes an interaction of the hypothalamic-pituitary axis with the adrenal medulla via mediators of the unspecific immune system", "The purpose of this study was to assess the effectiveness of music therapy in decreasing anxiety in ventilator-dependent patients.\n A crossover repeated measures design with random assignment was used.\n The intensive care unit of a university hospital in Hong Kong was used as the setting for this study.\n Twenty patients who were ventilator-dependent were recruited for the study. They were all Chinese with a mean age of 58.25 years (range, 19-84 y). Most (75%) were men. Outcome Measures: Physiologic measures of anxiety assessed in this study were mean blood pressure and respiratory rate. An additional measure was the Chinese version of the Spielberger State-Trait Anxiety Inventory.\n Patients were randomized to receive either 30 minutes of uninterrupted rest and then 30 minutes of music therapy or the music therapy first and then the uninterrupted rest period. Patients listened to relaxing music by using audiocassette players and headphones. Subjects selected the music of their choice from a selection including both Chinese and Western music. Subjects had physiologic measures taken immediately before the intervention (or rest period) and at 5-minute intervals throughout the intervention. The Chinese version of Spielberger's State-Trait Anxiety Inventory was completed before the intervention and immediately after the intervention.\n Findings indicated that music therapy was more effective in decreasing state anxiety than was an uninterrupted rest period (P <.01). As measured by analysis of variance with repeated measures, blood pressure and respiratory rate showed no significant differences in the 2 conditions over time. However, significant differences were observed at the end of the intervention (after 30 minutes) between the 2 conditions, with music therapy being superior to the rest period.\n Music therapy is an effective nursing intervention in decreasing anxiety in ventilator-dependent patients and its use should be incorporated into the care of mechanically ventilated patients. For the Chinese patients, culture and language were the predominant factors in their choice of music." ]

[ "6307516", "9470828", "8069603", "9857997", "7707405" ]

[ "Value of prophylactic cranial irradiation given at complete remission in small cell lung carcinoma.", "Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC)", "Comparative study of prophylactic cranial irradiation in patients with small cell lung cancer achieving a complete response: a long-term follow-up result.", "Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.", "Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission." ]

[ "The optimal use of \"prophylactic\" cranial irradiation (PCI) in patients with small cell lung cancer remains undetermined. This study reviews the impact of PCI, given at complete remission (CR), on neurologic relapse in 172 consecutive patients with small cell lung cancer treated in three sequential chemotherapy protocols at the University of Maryland Cancer Center. In the first study of 38 patients, none received PCI. In the second study of 109 patients, the first 28 achieving CR were randomized to 3000 rad of PCI in ten fractions (PCI+) or to observation (PCI-). Thereafter, based on interim analysis, all patients achieving CR received PCI. In the third study, to date, 25 patients achieving CR have received PCI. Overall, 169 patients were evaluable for neurologic relapse, and 30 of 90 patients achieving CR received PCI. Among all patients with CR, with adjustment for disease extent, there was a significant delay to any neurologic relapse (P = 0.01) and cerebral metastases (P = 0.02) for PCI+ compared to PCI- patients. Among PCI- patients with CR, cerebral metastases alone occurred in 28% as the sole site and in 33% as the initial site, whereas cerebral relapse occurred prior to systemic relapse in only one PCI+ patient with CR. Patient survival however, was not significantly altered by PCI. PCI at CR confers effective and worthwhile local control in the CNS, especially during periods of systemic response, and a small percentage of patients may benefit. Systemic drug resistance still determines overall survival.", "Prophylactic cranial irradiation (PCI) reduces the risk of cranial metastasis in small cell lung cancer (SCLC), but the magnitude and value of this reduction, the risks of radiation morbidity and whether PCI influences survival are unclear. We conducted a randomised trial in patients with limited-stage SCLC who had had a complete response to induction therapy. Initially, patients were randomised equally to (1) PCI 36 Gy in 18 daily fractions, (2) PCI 24 Gy in 12 fractions and (3) no PCI; subsequently, to increase the rate of accrual, randomisation was to clinicians' choice of PCI regimen versus no PCI (at a 3:2 ratio). The endpoints were appearance of brain metastases, survival, cognitive function, and quality of life (QoL). Three hundred and fourteen patients (194 PCI, 120 No PCI) were randomised. In the revised design, the most commonly used PCI regimens were 30 Gy in 10 fractions and 8 Gy in a single dose. With PCI, there was a large and highly significant reduction in brain metastases (HR = 0.44, 95% CI 0.29-0.67), a significant advantage in brain-metastasis-free survival (HR = 0.75, 95% CI 0.58-0.96) and a non-significant overall survival advantage (HR = 0.86, 95% CI 0.66-1.12). In both groups, there was impairment of cognitive function and QoL before PCI and additional impairment at 6 months and 1 year, but no consistent difference between the two groups and thus no evidence over 1 year of major impairment attributable to PCI. PCI can safely reduce the risk of brain metastases. Further research is needed to define optimal dose and fractionation and to clarify the effect on survival. Patients with SCLC achieving a complete response to induction therapy should be offered PCI.", "Between 1981 and 1986, a total of 46 patients with small cell lung cancer (SCLC) achieving a complete response by chemotherapy with or without chest irradiation were randomized either to receive prophylactic cranial irradiation (PCI) or not. With a median follow-up time of 8.5 years for both groups, only five of 23 patients (22%) in the PCI group developed brain relapse, while 12 out of 23 (52%) in the no PCI group did so (P < 0.05). The frequency of patients developing a sole brain relapse during their whole clinical course was 4% for the PCI group and 17% for the no PCI group, however, the difference was not statistically significant. Patient survival was better for the PCI group (median survival time of 21 months, and 5-year survival rate of 22%) as compared with the no PCI group (median survival time of 15 months, and 5-year survival rate of 13%), showing a marginal significance (P = 0.097). Late neurologic toxicity was infrequent; only one developed a mild deterioration among seven long-term disease-free survivors in the PCI group. These results appear to warrant further clinical trials to clarify the utility of PCI in patients with SCLC achieving a complete response.", "We conducted a randomised clinical trial on 211 patients with small-cell lung cancer in complete remission (CR). The aim of this trial was to evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival. Eligible patients were randomly assigned to receive either PCI (100 patients) or no PCI (111 patients). Each centre was allowed to use its own PCI protocol as long as the total dose was within the range of 24-30 Gy and delivered in less than 3 weeks with fractions of 3 Gy or less. The mean follow-up is 5 years. The survival curves do not differ significantly (P = 0.25) between the two groups. The 4-year overall survival rate (95% confidence interval) is 22% [15-32%] in the PCI group versus 16% [10-25%] in the control group. The relative risk of death in the PCI group compared to the control group is 0.84 (95% CI = [0.62-1.13]). The incidence of brain metastasis is lower in the PCI group, but the difference is not statistically significant (P = 0.14). The 4-year cumulative rate of brain metastasis is 44% [32-57%] in the PCI group compared to 51% [38-63%] in the control group. In conclusion, in this study, which had to be closed prematurely, no significant difference was found in terms of the incidence of brain metastases nor in survival.", "Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival. It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans. However, other retrospective data suggested a beneficial effect on overall survival for patients in complete remission.\n Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall survival, and late-occurring toxic effects in patients with small-cell lung cancer in complete remission.\n We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission. The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (control group). A neuropsychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6, 18, 30, and 48 months. Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse, using a competing-risk approach.\n Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed. The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45% in the control group and 19% in the treatment group (P < 10(-6)). The total 2-year rate of brain metastasis was 67% and 40%, respectively (relative risk = 0.35; P < 10(-13)). The 2-year overall survival rate was 21.5% in the control group and 29% in the treatment group (relative risk = 0.83; P = .14). There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans.\n Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications. A possible beneficial effect on overall survival should be tested with a higher statistical power.\n The results of the trial favor, at present, the indication of prophylactic cranial irradiation for patients who are in complete remission. A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission, and a meta-analysis of similar trials is recommended." ]

[ "22128654", "17666608" ]

[ "A randomized clinical trial of group prenatal care in two military settings.", "Group prenatal care and perinatal outcomes: a randomized controlled trial." ]

[ "A 3-year randomized clinical trial was conducted to test for differences in perinatal health behaviors, perinatal and infant health outcomes, and family health outcomes for women receiving group prenatal care (GPC) when compared to those receiving individual prenatal care. Women in GPC were almost 6 times more likely to receive adequate prenatal care than women in individual prenatal care and significantly more satisfied with their care. No differences were found by group for missed days of work, perceived stress, or social support. No differences in prenatal or postnatal depression symptoms were found in either group; however, women in GPC were significantly less likely to report feelings of guilt or shame. The findings suggest that women in GPC have more adequate care and no untoward effects were found with the model. Further study is important to evaluate long-term outcomes of GPC.", "To determine whether group prenatal care improves pregnancy outcomes, psychosocial function, and patient satisfaction and to examine potential cost differences.\n A multisite randomized controlled trial was conducted at two university-affiliated hospital prenatal clinics. Pregnant women aged 14-25 years (n=1,047) were randomly assigned to either standard or group care. Women with medical conditions requiring individualized care were excluded from randomization. Group participants received care in a group setting with women having the same expected delivery month. Timing and content of visits followed obstetric guidelines from week 18 through delivery. Each 2-hour prenatal care session included physical assessment, education and skills building, and support through facilitated group discussion. Structured interviews were conducted at study entry, during the third trimester, and postpartum.\n Mean age of participants was 20.4 years; 80% were African American. Using intent-to-treat analyses, women assigned to group care were significantly less likely to have preterm births compared with those in standard care: 9.8% compared with 13.8%, with no differences in age, parity, education, or income between study conditions. This is equivalent to a risk reduction of 33% (odds ratio 0.67, 95% confidence interval 0.44-0.99, P=.045), or 40 per 1,000 births. Effects were strengthened for African-American women: 10.0% compared with 15.8% (odds ratio 0.59, 95% confidence interval 0.38-0.92, P=.02). Women in group sessions were less likely to have suboptimal prenatal care (P<.01), had significantly better prenatal knowledge (P<.001), felt more ready for labor and delivery (P<.001), and had greater satisfaction with care (P<.001). Breastfeeding initiation was higher in group care: 66.5% compared with 54.6%, P<.001. There were no differences in birth weight nor in costs associated with prenatal care or delivery.\n Group prenatal care resulted in equal or improved perinatal outcomes at no added cost.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00271960\n I." ]

[ "17301567", "15764856", "11399987", "8652692", "20163346", "14660141", "11231872", "16421803", "17347877", "11131736", "15843107", "17991688", "16451341", "10963246", "9810402", "19623481" ]

[ "HIV incidence during a cluster-randomized trial of two strategies providing voluntary counselling and testing at the workplace, Zimbabwe.", "Voluntary HIV counseling and testing acceptance, sexual risk behavior and HIV incidence in Rakai, Uganda.", "Positive and negative life events after counselling and testing: the Voluntary HIV-1 Counselling and Testing Efficacy Study.", "Sexual risk behaviour reduction associated with voluntary HIV counselling and testing in HIV infected patients in Thailand.", "Does HIV VCT reduce risk behaviors? An observational study in Guatemala City.", "HIV incidence and risk behaviours after voluntary HIV counselling and testing (VCT) among adults aged 19-35 years living in peri-urban communities around Chiang Mai city in northern Thailand, 1999.", "Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a testing and counselling programme for men.", "Voluntary counseling and testing by nurse counselors: what is the role of routine repeated testing after a negative result?", "HIV voluntary counseling and testing among injection drug users in south China: a study of a non-government organization based program.", "Rapid voluntary testing and counseling for HIV. Acceptability and feasibility in Zambian antenatal care clinics.", "Acceptability of HIV/AIDS counseling and testing among premarital couples in China.", "Behaviour change in clients of health centre-based voluntary HIV counselling and testing services in Kenya.", "Condom use after voluntary counselling and testing in central Mozambique.", "Efficacy of voluntary HIV-1 counselling and testing in individuals and couples in Kenya, Tanzania, and Trinidad: a randomised trial. The Voluntary HIV-1 Counseling and Testing Efficacy Study Group.", "Impact of HIV counselling and testing on HIV seroconversion and reported STD incidence among male factory workers in Harare, Zimbabwe.", "Patterns of self-reported behaviour change associated with receiving voluntary counselling and testing in a longitudinal study from Manicaland, Zimbabwe." ]

[ "To investigate HIV incidence during a trial of two voluntary counselling and testing (VCT) strategies. Counselling may promote beneficial behavioural change, although knowledge of negative status does not appear to contribute further benefit.\n The parent cluster-randomized trial demonstrated much greater uptake of VCT when counselling and rapid testing were available on-site (intensive VCT) than through pre-paid vouchers to an external provider (standard VCT). Anonymous HIV tests had been requested from all employees at enrolment and after 2 years intervention.\n The study setting was 22 businesses in Harare, Zimbabwe. Participants were 3146 HIV-negative individuals remaining in employment at the end of intervention, of whom 2966 (94.3%) consented to repeat testing. VCT linked to basic HIV care was provided and the main outcome measures were HIV incidence under each study arm, as a retrospective secondary analysis.\n Mean VCT uptake in this cohort was 70.7 and 5.2%, respectively, in the intensive and standard arms. Crude HIV incidence was 1.21 per 100 person-years, with non-significantly higher rates in the intensive VCT arm [mean site incidence 1.37 and 0.95 per 100 person-years, respectively; adjusted rate ratio 1.49 (95% confidence interval 0.79-2.80).\n Highly acceptable VCT did not reduce HIV incidence in this predominantly male cohort. HIV incidence was highest in the high uptake VCT arm, lending support to a US trial in which rapid testing appeared to have adverse behavioural consequences in some HIV-negative clients. Careful comparison of outcomes under different counselling and testing strategies is needed to maximize HIV prevention from global scale-up of VCT.", "To assess the acceptance of voluntary HIV counseling and testing (VCT) and the effects of VCT on sexual risk behavior and HIV acquisition in Rakai, Uganda.\n In a rural cohort, 10 694 consenting adults were interviewed, provided blood for HIV testing and were offered free VCT by community resident counselors. The proportions receiving VCT and the adjusted risk ratio (adj. RR) of VCT acceptance were estimated by log binomial regression. Risk behaviors and HIV incidence per 100 person-years (PY) in HIV-negative acceptors and non-acceptors of VCT were assessed prospectively.\n Although 93% initially requested HIV results, 62.2% subsequently accepted VCT. VCT acceptance was lower among persons with no prior VCT [Adj. RR = 0.88; 95% confidence interval (CI), 0.85-0.90], individuals with primary education (adj. RR = 0.94; 95% CI, 0.90-0.99) or higher (adj. RR = 0.91; 95% CI, 0.87-0.97), individuals who were HIV-positive (adj. RR = 0.72; 95% CI, 0.68-0.76), and persons reporting condom use in the past 6 months (inconsistent users, adj. RR = 0.95; 95% CI, 0.90-0.99; consistent users, adj. RR = 0.88; 95% CI, 0.82-0.95). VCT acceptance was higher among the currently married (adj. RR = 1.14; 95% CI, 1.08-1.20) and previously married (adj. RR = 1.11; 95% CI, 1.04-1.18). Receipt of results was not significantly associated with age, gender, and self-perception of HIV risk. There were no significant differences in sexual risk behaviors, or in HIV incidence between acceptors (1.6/100 PY) and non-acceptors (1.4/100 PY) of VCT.\n In this rural cohort where VCT services are free and accessible, there is self-selection of individuals accepting VCT, and no impact of VCT on subsequent risk behaviors or HIV incidence.", "The results of the Voluntary HIV-1 Counselling and Testing Efficacy Study support the efficacy and cost-effectiveness of HIV voluntary counselling and testing (VCT) for reducing risk behaviors in three developing countries.\n This report explores the social consequences of HIV VCT by examining the incidence of positive and negative life events at the first follow-up (an average of 7.3 months after recruitment). The incidence of positive and negative life events was compared between: (i) those who were randomly assigned to HIV VCT versus health information (HI); (ii) those who tested seronegative and those who tested seropositive; and (iii) those who disclosed their serostatus and those who did not.\n The occurrence of most negative life events was rare (0--4%); positive life events were more common (17--39%). With few exceptions, those assigned to HIV VCT were no more likely to experience negative life events than those who were assigned to HI. For individuals, positive serostatus was associated with increased support from health professionals, the break-up of a marriage and being neglected or disowned by their family. Serodiscordant couples with an HIV-positive woman were most likely to report the break-up of a marriage (20 versus 0--7% for other groups) and the break-up of a sexual relationship (45 versus 22--38% for other groups). Disclosure was associated with strengthening of a sexual relationship except for HIV-seropositive women.\n These findings, in combination with findings supporting the efficacy and cost-effectiveness of HIV VCT, support the dissemination of HIV VCT with appropriate support services in developing countries.", "Sexual risk behaviour, measured by anonymously self-reported sexual activity, number of sexual partners, and condom use rates, was studied in age- and gender-matched HIV-1 positive consecutive patients from the Thai Red Cross Immune Clinic (IC) (study group, questioned after voluntary HIV counselling and testing) and the Thai Red Cross Anonymous Clinic (AC) (control group, questioned before voluntary HIV counselling and testing) in Bangkok, Thailand in 1993/94. More than 80% of study patients reported having decreased their sexual activity and their number of sexual partners since receipt of the positive HIV test result. Compared to control patients, study patients reported more often abstaining from sex (42% vs 14%), and more often using condoms during all their last three incidences of sexual intercourse (44% vs 14%). These findings give evidence for the value of voluntary HIV counselling and testing in contributing to the reduction of HIV transmission in Asia.", "We examined the impact of HIV voluntary counseling and testing on self-reported behavioral risks three months after HIV testing.\n Cohort study comparing self-reported risk behaviors prior to and three months after HIV testing. Setting: Clinica Familiar Luis Angel Garcia, an HIV specialty clinic located in a Guatemalan National Hospital.\n 144 people undergoing HIV testing were enrolled. 44 were HIV positive. 41 HIV positive and 49 HIV negative subjects returned for follow-up interviews. Intervention: All subjects were tested and received voluntary counseling regarding HIV infection, transmission, prevention, and interpretation of HIV test results.\n The primary study outcome measure was change in self-reported risk behaviors three months after voluntary counseling and testing.\n Men were more likely than women to report a history of sexually transmitted diseases, more than 2 sexual partners, using alcohol with sex, and receiving money for sex; they were less likely to have a regular partner. 26% of men reported non-heterosexual orientation; no woman did. Alcohol was the primary drug of abuse in both men and women. At three month follow-up HIV positive subjects showed decreases in the average number of sexual partners, use of alcohol with sex, and episodes of unprotected sex.\n Voluntary counseling and testing resulted in changes in some self-reported risk behaviors, but only among HIV positive subjects. On nearly all measures men report riskier behavior than women. Alcohol is the most commonly used drug in this population and is often used with sex.", "The Thai government began HIV voluntary counselling and testing (VCT) in all provinces in 1992. We evaluated HIV incidence after participants utilized VCT and its effect on risk behaviours among northern Thai adults aged 19-35 years. A total of 924 men and 1,327 women volunteered to participate in the study. Subjects were counseled, interviewed (socio-demographic, HIV risk behaviour, and HIV testing history), and tested for HIV infection at baseline and at 6 months follow-up. All participants were provided group pre-test counselling; HIV test results were provided in individual confidential post-test counselling. Overall, 329 of 391 men and 621 of 669 women who reported a prior HIV test before participating in our study reported negative results at the previous test. Of these, nine men and 13 women tested positive at baseline, giving incidence rates of 1.04 and 0.69 per 100 person years (PY), respectively. Recent risk behaviour was rare; as a result, the effects of VCT on risk behaviours among the study participants could not be determined. The HIV incidence after VCT among this study population is substantial. Studies to investigate factors associated with HIV incidence among VCT clients could provide insights for more effective HIV prevention.", "As part of a longitudinal investigation, the husbands and cohabiting male partners of 684 Rwandan women were recruited to participate in an HIV testing and counselling programme. All of the women and 256 of the men (37%) had previously received standard testing and generic counselling services. In this project, all of the men participated in an extensive, male-focused counselling programme. This included 428 men who were receiving testing and counselling for the first time. Interview responses indicated that rates of condom use during sexual intercourse increased dramatically at the one-year follow-up assessment for the serodiscordant couples. This effect was especially strong for couples whose male partners were receiving testing and counselling for the first time. Rates of condom use also increased substantially in seroconcordant HIV-positive couples whose partners had both been tested previously. Women in couples with at least one seropositive partner reported lower rates of coercive sex by their male partners after they completed the counselling programme. Male-focused and couple-focused testing and counselling programmes appear to be effective in reducing risky sexual behaviours in heterosexual couples, even if one or both partners have received testing and counselling services previously.", "Three hundred eighty-eight human immunodeficiency virus (HIV)-negative clients in Zimbabwe were retested at 3 months using 2 parallel rapid tests. One operator error (risk, 0.26%; 95% confidence interval, 0.0065%-1.4%) and no \"true\" seroconversions (upper 95% confidence limit, 0.96%) were detected. High-risk behavior was not significantly reduced. Policies recommending routine retesting need to be reconsidered.", "HIV voluntary counseling and testing (VCT) programs are usually delivered by government health agencies in China. This study examined the feasibility of using a Chinese non-government organization (NGO) to deliver a VCT program to injection drug users (IDUs) in a southern Chinese city. The process data indicated the program successfully recruited and served 226 male and female IDUs in 4 months. The HIV prevalence rate of the study population was 57.5% by rapid HIV testing with a secondary rapid test to confirm. Quantitative and qualitative evaluations indicated that the VCT program was implemented appropriately and participants' HIV knowledge and safe drug and sex practices were significantly improved after participation in the VCT program. This study demonstrates the feasibility of a Chinese NGO to provide VCT for IDUs and documents the processes and outcomes of the program. There remains a great need to find additional sources to provide VCT and other HIV prevention services to IDUs and other high-risk populations in China. Chinese NGOs have the potential to fill this need.", "Voluntary testing and counseling (VTC) for HIV/AIDS is now widely accepted as an effective HIV prevention and control strategy among heterosexual couples in sub-Saharan Africa. The most appropriate format and venue for VTC remains a topic of debate among clinicians and public health professionals. Our research done in Lusaka, Zambia, took a tripartite approach to exploring the most acceptable format and venue for VTC: a community survey of attitudes towards VTC, a pre- and postcounseling knowledge survey, and a pilot study of same-day VTC in urban antenatal care clinics. A community survey of 181 individuals was conducted in July-August 1996 based on a structured questionnaire. A pre- and post-VTC intervention knowledge survey was conducted during the same period among 82 couples attending the Zambia-UAB HIV Research Project (ZUHRP) HIV VTC center in Lusaka. Finally, same-day HIV VTC was pilot tested in six antenatal clinic locations during February-May 1997 and June-August 1998. The community survey revealed that 98% of participants support promotion of HIV VTC in the community and 83.8% prefer the same-day testing format. The knowledge survey revealed misconceptions about discordance within a couple and perinatal transmission of HIV. Pilot testing in antenatal clinics was well received, with 84% of pregnant women requesting testing and 25% having positive HIV serologies. Women with primary school or less education, those seeking antenatal care in local clinics, and those seen before the third trimester of pregnancy were more likely to request HIV testing. Testing and counseling for HIV were shown to be feasible and effective in the antenatal clinic setting. Implementation of same-day HIV VTC in antenatal clinics is an effective strategy to prevent vertical transmission and should be expanded to include couples to leverage a decrease in heterosexual transmission as well.", "Premarital counseling is required for couples wishing to be married in China. The counseling primarily provides information about contraception. We evaluated adding premarital HIV/AIDS counseling and voluntary HIV testing to the standard counseling. The test was offered free to one group and at the standard cost to the other. The proportion of those accepting HIV testing among all participants receiving premarital counseling was used as a measure of acceptability. Sixteen percent of participants not charged chose to accept testing versus 1.4% of those charged ( p < .001). Lack of HIV/AIDS knowledge and charging for the test were correlated with refusal. Over 5% of participants admitted to premarital sex, most with their fianceé, and a significantly higher portion was female. Only 22% used condoms. Study participants were randomized for 1-year follow-up. Only four participants reported extramarital sexual activity during that year. Acceptance of HIV testing was disappointingly low. Implementing strategies to reduce stigmatization and increase knowledge of HIV/AIDS, in addition to not charging for testing, may increase the acceptance of HIV testing.", "To explore behaviour change, baseline risk behaviour, perception of risk, HIV disclosure and life events in health centre-based voluntary counselling and testing (VCT) clients.\n Single-arm prospective cohort with before-after design at three (one urban and two rural) government health centres in Kenya; study duration 2 years, 1999-2001.\n Consecutive eligible adult clients.\n Numbers of sexual partners, partner type, condom use, reported symptoms of sexually transmitted infection, HIV disclosure and life events.\n High rates of enrollment and follow-up provided a demographically representative sample of 401 clients with mean time to follow-up of 7.5 months. Baseline indicators showed that clients were at higher risk than the general population, but reported a poor perception of risk. Clients with multiple partners showed a significant reduction of sexual partners at follow-up (16% to 6%; p<0.001), and numbers reporting symptoms of sexually transmitted infection decreased significantly also (from 40% to 15%; p<0.001). Condom use improved from a low baseline. Low rates of disclosure (55%) were reported by HIV-positive clients. Overall, no changes in rates of life events were seen.\n This study suggests that significant prevention gains can be recorded in clients receiving health centre-based VCT services in Africa. Prevention issues should be considered when refining counselling and testing policies for expanding treatment programmes.", "To evaluate the efficacy of voluntary counselling and testing (VCT) for HIV/AIDS in changing risky sexual behaviour in central Mozambique.\n Longitudinal cohort study of men and women aged at least 18 years from October 2002 to June 2003. We interviewed 622 participants in VCT groups and 598 in non-VCT groups. The interviews occurred before counselling and 4 and 6 months afterwards.\n Reported use of condoms while having sex with a friends/prostitute increased over each time period in the VCT group and between baseline and first visit in the non-VCT group. Both men and women in the VCT group increased their condom use over time, but the women in the non-VCT group did not. Reported always/sometimes use of condoms for both literate and illiterate subjects was higher and rose over time in the VCT group.\n People who undergo voluntary counselling and testing fro HIV/AIDS change their behaviour, presumably as a result of their counselling.", "Our aim was to determine the efficacy of HIV-1 voluntary counselling and testing (VCT) in reducing unprotected intercourse among individuals and sex-partner couples in Nairobi (Kenya), Dar es Salaam (Tanzania), and Port of Spain (Trinidad).\n Individual or couple participants were randomly assigned HIV-1 VCT or basic health information. At first follow-up (mean 7.3 months after baseline) health-information participants were offered VCT and all VCT participants were offered retesting. Sexually transmitted infections were diagnosed and treated at first follow-up. The second follow-up (mean 13.9 months after baseline) involved only behavioural assessment, and all participants were again offered VCT.\n 3120 individuals and 586 couples were enrolled. The proportion of individuals reporting unprotected intercourse with non-primary partners declined significantly more for those receiving VCT than those receiving health information (men, 35% reduction with VCT vs 13% reduction with health information; women, 39% reduction with VCT vs 17% reduction with health information), and these results were maintained at the second follow-up. Individual HIV-1-infected men were more likely than uninfected men to reduce unprotected intercourse with primary and non-primary partners, whereas HIV-1-infected women were more likely than uninfected women to reduce unprotected intercourse with primary partners. Couples assigned VCT reduced unprotected intercourse with their enrolment partners significantly more than couples assigned health information, but no differences were found in unprotected intercourse with non-enrolment partners. Couples in which one or both members were diagnosed with HIV-1 were more likely to reduce unprotected intercourse with each other than couples in which both members were uninfected. These changes were replicated by those in the health-information group diagnosed with HIV-1 at first follow-up.\n These data support the efficacy of HIV-1 VCT in promoting behaviour change.", "To assess the impact of HIV counselling and testing on HIV seroconversion and incidence of reported sexually transmitted diseases (STDs) among male factory workers in Harare, Zimbabwe.\n Prospective, observational study among men recruited to participate in a future workplace based AIDS prevention intervention.\n Participants provided STD histories and blood for HIV antibody testing at enrolment and six month intervals during visits to factories. Participants received HIV test results, post test counselling, and free STD services at the project clinic.\n Between March 1993 and June 1995, 2,414 men were enrolled with 85% follow up. Overall HIV sero-incidence was 2.60 per 100 person-years; the incidence of reported STDs was 10.19 per 100 person-years. Men who obtained their HIV test results had significantly higher HIV sero-incidence and incidence of reported STDs compared to men who did not obtain their results (IRRs: 1.87, 3.47, respectively). Among men who obtained their HIV test results, a non-significant 40% decrease in HIV sero-incidence was observed after obtaining test results compared to before obtaining results (p = 0.18). The incidence of reported STDs, however, increased by 30% after obtaining HIV test results (p = 0.10).\n Decreased HIV sero-incidence in the face of increased reported STD incidence suggests that timely treatment of STDs may decrease the risk of acquiring HIV even in the absence of behaviour change. In populations with high rates of HIV and STDs, the greatest benefit of HIV counselling and testing may be achieved by simultaneously offering STD screening and treatment services.", "Voluntary counselling and testing (VCT) is promoted as a potential HIV prevention measure. We describe trends in uptake of VCT for HIV, and patterns of subsequent behaviour change associated with receiving VCT in a population-based open cohort in Manicaland, Zimbabwe. The relationship between receipt of VCT and subsequent reported behaviour was analysed using generalized linear models with random effects. At the third survey, 8.6% of participants (1,079/12,533), had previously received VCT. Women who received VCT, both those positive and negative, reduced their reported number of new partners. Among those testing positive, this risk reduction was enhanced with time since testing. Among men, no behavioural risk reduction associated with VCT was observed. Significant increases in consistent condom use, with regular or non-regular partners, following VCT, were not observed. This study suggests that, among women, particularly those who are infected, behavioural risk reduction does occur following VCT." ]

[ "4875817", "335788", "8120154", "8151005", "7009592", "9054788", "7440519", "4964946", "2198301", "5326793", "8328559", "11000645", "9246253", "7008890", "1903019", "6337580", "7016802", "9347378", "2248066", "2099360" ]

[ "Iprindole in neurotic depressed general practice patients: a controlled study.", "Pizotifen as an antidepressant.", "Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder.", "Duration of antidepressant trials: clinical and research implications.", "Maprotiline versus imipramine and placebo in neurotic depression.", "Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes.", "Trazodone in the treatment of neurotic depression.", "A controlled evaluation of U-23,807A in the neurotic depressive syndrome.", "Buspirone therapy in anxious elderly patients: a controlled clinical trial.", "[Comparative evaluation of the antidepressive properties of opipramol, imipramine and placebo in neurotic depression].", "A randomized double-blind study of fluoxetine versus placebo in the treatment of dysthymia.", "Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults.", "Controlled efficacy study of fluoxetine in dysthymia.", "Viloxazine in the treatment of depressive neurosis: a controlled clinical study with doxepin and placebo.", "5-HT2 receptor antagonism in dysthymic disorder: a double-blind placebo-controlled study with ritanserin.", "Efficacy of desipramine in depressed outpatients. Response according to research diagnosis criteria diagnoses and severity of illness.", "Viloxazine in the treatment of depressive neurosis: a placebo and standard (imipramine) controlled clinical study.", "Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group.", "Moclobemide versus placebo in the treatment of depression: a multicentre study in Belgium.", "Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders." ]

[ "nan", "In a double-blind study the therapeutic effect and tolerance of pizotifen was compared with placebo in 20 outpatients of both sexes suffering from light to moderate depression. Pizotifen seems to possess certain antidepressive effects in dosages of 4-10 mg daily. These properties, and the well-documented effect of pizotifen in migraine, could make it an alternative in treating patients suffering from the often seen combination of vascular headache/depression.", "Fifty outpatients with dysthymic disorder (DSM-III) were divided by double-blind randomized assignment into three groups given ritanserin, imipramine, and placebo, respectively. The trial was of 7 weeks' duration; by week 6, imipramine was clearly superior to placebo, whereas by week 7, both drugs caused significantly more improvement than the placebo. Although imipramine had slightly greater efficacy than ritanserin, it also had significantly more side effects. This was particularly evident in the higher dropout rate with imipramine. The efficacy and side effect profile of ritanserin makes it well tolerated and acceptable with dysthymic patients who, although they do not respond as quickly as patients with major depressive disorder, do show significant improvement, given sufficient time.", "The objective of our study was to demonstrate that additional antidepressant benefit occurs between weeks 4 and 6 in adult outpatients, even when dose is not increased. Response between weeks 4 and 6 was studied among depressed outpatients randomly assigned to imipramine, phenelzine, or placebo under double-blind conditions. Patients were selected for analysis only if they did not have a dose increase after the start of the fourth week of treatment (day 22). Eighty-eight patients met this condition. Conditional probability analysis was performed. Nonresponders to 4 weeks (28 days) of treatment had a significantly greater likelihood of responding by week 6 if they were on phenelzine rather than placebo. The same is probably true for patients on imipramine. In research and clinical care, 4 weeks is too short a trial of phenelzine to conclude a lack of efficacy. Four weeks is probably also too short a trial of imipramine.", "The antidepressant effect of maprotiline, a tetracyclic compound, was compared with that of imipramine in a four-week, double-blind, placebo controlled study with neurotic depressives. On all factors of the Hamilton Depression Rating Scale and on most items of the Zung Self-Rating Scales for Depression and Anxiety, maprotiline appeared slightly more effective than imipramine and showed a faster onset of action. In addition, it appeared to cause fewer anticholinergic side effects.", "The purpose of this study was to determine the effects of antidepressant pharmacotherapy on mood symptoms and psychosocial outcomes in dysthymia.\n In a multicenter, double-blind, parallel-group trial, 416 patients with a diagnosis of early-onset primary dysthymia (DSM-III-R) of at least 5 years' duration without concurrent major depression were randomly assigned to 12 weeks of acute-phase therapy with sertraline, imipramine, or placebo. The psychosocial outcome measures used in the study were the Global Assessment of Functioning Scale, the Social Adjustment Scale, the Longitudinal Interval Follow-up Evaluation psychosocial ratings, and the Quality of Life Enjoyment and Satisfaction Questionnaire.\n Sertraline and imipramine were significantly better than placebo in improving psychosocial outcomes as measured by the first three instruments. The Quality of Life Enjoyment and Satisfaction Questionnaire scores demonstrated significant improvements from baseline, and both active treatments produced significantly greater improvements than placebo. Significantly fewer patients discontinued sertraline (6.0%) than discontinued imipramine (18.4%) because of adverse events.\n Pharmacotherapy is an effective treatment for dysthymia in terms of psychosocial functioning as well as depressive symptoms, even when the dysthymia is long-standing.", "A double-blind study was conducted to determine the efficacy and safety of trazodone vs. amitriptyline and placebo in 184 patients suffering from neurotic depression. All patients were evaluated for safety and 127 patients who completed 12 to 42 days' therapy were evaluated for efficacy. Trazodone was found to be significantly better than placebo on almost every rating scale, particularly on those items or factors related to depression and associated anxiety. Trazodone was superior to amitriptyline in some patients while amitriptyline was only occasionally better than placebo. Significant improvement was noted in trazodone patients within the first seven days of therapy. Trazodone produced a low level of side effects compared to amitriptyline.", "nan", "Forty patients over 65 years of age with anxiety symptoms due to an anxiety state (N = 20) or secondary to neurotic depression (N = 20) took part in a double-blind, placebo-controlled trial conducted in a primary care practice. All patients were receiving concomitant drug therapy for chronic medical conditions; 70% were receiving two or more nonpsychotropic drugs in addition to the study medication. Patients were randomly assigned to treatment with buspirone 5-30 mg/day or placebo for 4 weeks, with clinical evaluations made weekly. One buspirone-treated and two placebo-treated patients discontinued treatment after 2 weeks because of lack of efficacy. Buspirone treatment resulted in significantly greater (p less than or equal to 0.05) improvement on the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression assessment than did placebo. Mild adverse experiences were reported by five buspirone-treated and nine placebo-treated patients. Buspirone (mean dose, 18 mg/day) proved equally effective for elderly patients suffering anxiety states or neurotic depression at doses similar to those used in younger patients, and was well tolerated by elderly patients receiving treatment for other chronic medical conditions.", "nan", "The purpose of this study was to assess the efficacy of fluoxetine, a selective serotonergic antidepressant, in the treatment of dysthymia.\n Thirty-five patients who met criteria for dysthymia, but not major depression, began randomized, double-blind 8-week trials of fluoxetine or placebo.\n Of 32 patients who completed the study, 10 (62.5%) of the 16 patients given fluoxetine and three (18.8%) of the 16 given placebo responded to treatment. Response was defined as 1) 50% or greater decrease in Hamilton Rating Scale for Depression score and 2) a score of 1 or 2 on the Clinical Global Impression (CGI) improvement subscale. Fluoxetine subjects showed significantly greater improvement at week 8 than placebo subjects on the Hamilton depression and CGI scales, but not on the Hopkins Symptom Check-list (58-item) or the Cornell Dysthymia Rating Scale.\n When compared to placebo, fluoxetine showed short-term effectiveness in treating dysthymic symptoms.", "Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia.\n To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia.\n Randomized, placebo-controlled trial (November 1995-August 1998).\n Four geographically and clinically diverse primary care practices.\n A total of 415 primary care patients (mean age, 71 years) with minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed all study visits.\n Patients were randomly assigned to receive paroxetine (n = 137) or placebo (n = 140), starting at 10 mg/d and titrated to a maximum of 40 mg/d, or problem-solving treatment-primary care (PST-PC; n = 138). For the paroxetine and placebo groups, the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring; for the PST-PC group, visits were for psychotherapy.\n Depressive symptoms, by the 20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components.\n Paroxetine patients showed greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0. 07]; P =.004) symptom resolution than placebo patients. Patients treated with PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13]; P =.13), but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks (P =.01). For dysthymia, paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P =. 01) or intermediate (difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P =.03). Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo (P>/=.12 for low-, intermediate-, and high-functioning groups). For minor depression, both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning (difference vs placebo in mean [SE] change in SF-36 mental component scores, 4.7 [2.03] for those taking paroxetine; 4.7 [1.96] for the PST-PC treatment; P =.02 vs placebo).\n Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression. The benefits of PST-PC were smaller, had slower onset, and were more subject to site differences than those of paroxetine.", "There have been very few controlled studies of antidepressants in dysthymia, particularly in samples diagnosed reliably and with an adequate length of follow-up. In this investigation, we measured the long-term outcome in a large group of patients meeting DSM-III-R criteria for dysthymia. This study was designed to investigate whether fluoxetine is effective in the treatment of dysthymia.\n This randomised study including 140 patients, compared fluoxetine (91 patients) and placebo (49 patients) on a double-blind basis in two distinct phases: a short-term end-point (3 months with 20 mg/day fluoxetine) and a medium-term end-point (6 months) where the initial responders continued double-blind treatment unchanged and non-responders received an additional treatment of 20 mg/day fluoxetine.\n After three months of treatment, response was seen more frequently in the fluoxetine group (42/72) than in the placebo group (14/39, P < 0.0001). Improved patients at 3 months were still improved at 6 months. Furthermore, 50% of the nonresponders at 3 months improved and rated as responders at 6 months, after fluoxetine was increased to 40 mg daily.\n This study showed the significant and persistent action of fluoxetine on dysthymia. The finding that 50% of the non-responders at 3 months were improved at 6 months, after fluoxetine dosage was increased to 40 mg daily, argues in favour of treating dysthymic patients for at least 6 months, and with a higher dosage if the initial doses are ineffective.", "In a four-week, double-blind, clinical trial thirty-one patients with depressive neurosis were treated with viloxazine, doxepin, or placebo. There were no differences among the three groups in therapeutic effects. Many depressed out-patients improve on placebo. Viloxazine hydrochloride is one of a series of compounds developed to explore the central nervous system activity of the aryloxypropanolamine type of beta-adreno-receptor antagonists. Initial clinical study support the hypothesis that viloxazine has antidepressant properties in man (Bayliss et al, 1974; Bereen, 1973; Pichot et al., 1975; Tsegos and Ekdawi, 1974).", "Thirty patients suffering from dysthymic disorder participated in a 6-week double-blind trial comparing ritanserin 10 mg and placebo. After a single-blind placebo wash-out period of one week, the test medication was administered during 5 weeks on a double-blind basis. Twenty-three patients completed the study. At the end of the trial, ritanserin was significantly superior to placebo in its effect as manifested on the 19-item Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety and the State Trait Anxiety Inventory X-1 and X-2. At the end of the study, the therapeutic effect was rated marked or moderate in 75% of the ritanserin-treated patients, but only in 18% of the controls. These data are consistent with the hypothesis of serotonin abnormalities in dysthymic disorder and suggest a therapeutic role of 5-HT2 antagonists. Ritanserin treatment was very well tolerated; no serious adverse experiences were reported.", "The efficacy of desipramine for mild depression was tested in a double-blind, placebo-controlled study of outpatients with scores below 19 on the Hamilton Rating Scale for Depression (HAM-D). Of 103 such patients, 23 dropped out and 16 improved during a ten-day placebo period. Among 64 patients completing the randomized portion of the study, significantly more improved with desipramine that with placebo. The Research Diagnostic Criteria (RDC) category of major depressive disorder largely accounted for the drug-placebo response difference found for the entire sample. Patients with intermittent depressive disorder improved significantly less frequently with desipramine than patients with major depressive disorder. Independent of RDC diagnosis, severity of illness correlated with outcome. Thus, patients with pretreatment HAM-D scores at or above the median demonstrated significant drug effect, while patients with lower pretreatment HAM-D scores did not.", "In a 4-week double-blind trial, 33 patients with depressive neurosis were randomly assigned to either viloxazine, imipramine or placebo. Statistically significant improvement was observed in all treatment groups. Imipramine exhibited significant improvement earlier in depressive symptoms, while viloxazine showed significant improvement earlier in anxious symptoms. The same frequency of treatment emergent symptoms occurred in the treatment groups. Premature termination as a consequence of adverse reactions was required in only 1 viloxazine and 1 placebo patient.", "An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.", "Moclobemide was compared with placebo for antidepressant activity, tolerance and safety in 2 parallel groups of 23 and 24 depressed patients. At the end of treatment (4 weeks or longer), 9 patients on moclobemide (41%) showed an improvement greater than or equal to 50% on the Hamilton Rating Scale for Depression, compared with only 4 (17%) of those on placebo. The overall assessment of efficacy was significantly better for moclobemide (good or very good results in 50% of patients) than for placebo (80% poor results). Moclobemide was well or very well tolerated by 85% of patients and placebo by 100%. Moclobemide was thus shown to be clearly more effective than placebo and only slightly less well tolerated.", "Sixty senile subjects (60-80 years old) with dysthymic disturbances as defined by DSM III (Cat. 390.40) were randomized into two homogeneous groups, one of which was given acetyl-L-carnitine (3 g/day per os) while the other received a placebo. After a washout phase of one week, each patient was evaluated by scoring on the Hamilton Rating Scale for Depression and the Beck Depression Inventory, as well as the Sandoz Clinical Assessment-Geriatric. These tests were administered at the beginning of the trial, prior to drug administration, and repeated during the treatment phase after 30 and 60 days. The results showed that treatment with acetyl-L-carnitine induced a significant reduction, as compared to the placebo (p less than 0.002), in the severity of depressive symptoms and also a significant improvement (p less than 0.0027) in the items measuring the quality of life." ]

[ "15588235", "20463094", "16621910", "17284630" ]

[ "Effects of increased thyroxine dosage pre-conception on thyroid function during early pregnancy.", "Thyroid hormone early adjustment in pregnancy (the THERAPY) trial.", "Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications.", "The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies." ]

[ "To compare the effects of pregnancy on the serum free thyroxine (FT4) levels in two cohorts of primary hypothyroid women treated with different levothyroxine (L-T4) doses before gestation.\n Twenty-five women with compensated hypothyroidism of different aetiology (thyroidectomized and Hashimoto's thyroiditis) were enrolled in this prospective study. The women were receiving substitutive doses of L-T4 and were anticipating pregnancy. They were assigned to two groups: 14 patients (group I) were switched to partially suppressive treatment while 11 patients (group II) continued the same therapeutic regimen.\n Pre-conceptional thyroid function evaluation demonstrated significantly higher FT4 and lower TSH in group I (P<0.001, for both hormones) and comparable free 3,5,3'-triiodothyronine (FT3) levels. The first post-conception thyroid function evaluation occurred at a median time of 6 (5-8) and 7 (5-9) weeks of gestation, for groups I and II respectively (P<0.05); all women in group I showed adequate serum FT4 levels while three patients in group II showed low-normal FT4 levels and one case was below normal levels. Statistical analysis demonstrated significantly higher frequencies (0% vs 36.4%; P<0.05) of low-normal FT4 levels in patients receiving substitutive doses of L-T4. None of the Hashimoto's-affected patients showed low or low-normal serum FT4 levels regardless of their therapeutic regimen.\n Our results suggest that in hypothyroid women anticipating pregnancy (with serum TSH in the lower quartile of normal range), the pre-conception adjustment of L-T4 doses may result in adequate maternal thyroid function up to the first post-conception evaluation. The procedure seems safe and inexpensive; it may be a worthwhile treatment, at least in thyroidectomized women, in view of the well-known potential effects of even marginal maternal thyroid hypofunction on the subsequent IQ of the progeny.", "Thyroid hormone requirement increases 20-40% during gestation. Women with treated hypothyroidism must increase their l-T(4) in pregnancy to prevent maternal hypothyroidism, although how this should be accomplished is unclear.\n We prospectively enrolled 60 women with treated hypothyroidism seeking pregnancy. Once pregnant, women were randomized to increase l-T(4) by either two tablets/wk (group A) or three tablets/wk (group B). Thyroid function was tested biweekly through midpregnancy and at 30 wk gestation. Levothyroxine was adjusted to maintain goal TSH concentrations. The primary objective was to assess efficacy in preventing maternal hypothyroidism and the safety of this intervention.\n Forty-eight women completed the protocol. Increasing the l-T(4) dose once pregnant (regardless of study arm) prevented TSH elevation over 5.0 mIU/liter throughout the first trimester and replicated physiological changes of pregnancy. The early l-T(4) increase caused TSH suppression below 0.5 mIU/liter in eight of 25 women in group A compared with 15 of 23 women in group B (P < 0.01). This risk was significantly increased in athyreotic patients [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.1-11.1], those with prepregnancy TSH less than 1.5 mIU/liter (OR = 4.6; 1.3-16.2), and those receiving prepregnancy l-T(4) doses of 100 microg/d or more (OR = 7.2; 1.7-30.6). However, if a trimester-specific TSH lower reference range of 0.1 mIU/liter was used, only two patients (8%) in group A required dose reduction. TSH testing every 4 wk identifies 92% of abnormal values.\n A two-tablet increase in l-T(4) initiated at confirmation of pregnancy significantly reduces the risk of maternal hypothyroidism during the first trimester and mimics normal physiology. Monitoring TSH every 4 wk through midgestation is recommended.", "Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications.\n We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects.\n This was a prospective study.\n The study was conducted in the Department of Obstetrics and Gynecology.\n A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)).\n TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group.\n Rates of obstetrical complications in treated and untreated groups were measured.\n At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7).\n Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.", "Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis.\n We examined whether Se supplementation, during and after pregnancy, influences the thyroidal autoimmune pattern and function.\n This was a prospective, randomized, placebo-controlled study.\n The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology.\n A total of 2143 euthyroid pregnant women participated in the study; 7.9% were TPOAb(+).\n During pregnancy and the postpartum period, 77 TPOAb(+) women received selenomethionine 200 microg/d (group S1), 74 TPOAb(+) women received placebo (group S0), and 81 TPOAb(-) age-matched women were the control group (group C).\n We measured the prevalence of PPTD and hypothyroidism.\n PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 (28.6 vs. 48.6%, P<0.01; and 11.7 vs. 20.3%, P<0.01).\n Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism." ]

[ "11281957", "9892253", "8889288", "11870017", "10784481", "9836012", "8037263", "10071726", "9892252", "9892314", "10432468", "10553752", "11806864", "11593073" ]

[ "Double-blind, placebo-controlled, crossover trial of D-cycloserine adjuvant therapy for treatment-resistant schizophrenia.", "Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia.", "D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia.", "Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia.", "Placebo-controlled trial of glycine added to clozapine in schizophrenia.", "D-serine added to antipsychotics for the treatment of schizophrenia.", "Amelioration of negative symptoms in schizophrenia by glycine.", "A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia.", "A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia.", "Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia.", "D-cycloserine increases positive symptoms in chronic schizophrenic patients when administered in addition to antipsychotics: a double-blind, parallel, placebo-controlled study.", "D-serine added to clozapine for the treatment of schizophrenia.", "Adjunctive high-dose glycine in the treatment of schizophrenia.", "A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia." ]

[ "Dysfunction of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may be relevant to the pathogenesis of negative symptoms in schizophrenia. The tuberculostatic compound D-cycloserine (DCS) acts as a partial agonist at the strychnine-insensitive glycine regulatory site on the NMDA receptor complex. Dose-finding trials suggest that DCS doses of 50-100 mg/d may be beneficial in the treatment of negative symptoms in schizophrenia. Nine treatment-resistant chronic schizophrenic patients participated in a double-blind, placebo-controlled, adjuvant treatment trial with 50 mg/d DCS. Between treatment-groups differences in symptom changes were not significant. However, a significant (p<0.05) reduction in negative symptoms was registered during treatment with DCS but not placebo. Greater reductions were registered in patients with lower baseline serum glycine levels (p<0.008). No side effects were registered. These preliminary findings indicate a potential role of DCS in the treatment of negative symptoms in schizophrenia. However, the degree of symptom reduction may be modest, at least among treatment-resistant inpatients.", "Disturbances of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may play an important role in the pathophysiology of negative symptoms of schizophrenia. Glycine, a small nonessential amino acid, functions as an obligatory coagonist at NMDA receptors through its action at a strychnine-insensitive binding site on the NMDA receptor complex. Glycine-induced augmentation of NMDA receptor-mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia.\n Twenty-two treatment-resistant schizophrenic patients participated in a double-blind, placebo-controlled, 6-week, crossover treatment trial with 0.8 g/kg per day of glycine added to their ongoing antipsychotic medication. Clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Simpson-Angus Scale for Extrapyramidal Symptoms, and the Abnormal Involuntary Movement Scale, were performed biweekly throughout the study. Clinical laboratory values and amino acid serum levels were monitored.\n Glycine treatment was well tolerated and induced increased glycine (P=.001) and serine (P=.001) serum levels. Glycine administration resulted in (1) a significant (P<.001) 30%+/-16% reduction in negative symptoms, as measured by the PANSS, and (2) a significant (P<.001) 30%+/-18% improvement in the BPRS total scores. The improvement in negative symptoms was unrelated to alterations in extrapyramidal effects or symptoms of depression. Low pretreatment glycine serum levels significantly predicted (r= 0.80) clinical response.\n These findings support hypoglutamatergic hypotheses of schizophrenia and suggest a novel approach for the pharmacotherapy of negative symptoms associated with this illness.", "This preliminary investigation examined the therapeutic efficacy of two doses of oral D-cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D-Cycloserine is an agonist at the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor complex. An NMDA agonist intervention was studied because of the schizophreniform psychosis precipitated by phencyclidine (PCP), which is a noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of schizophrenia is regarded as the most comprehensive pharmacological model of this disorder. In this preliminary, placebo-controlled, double-blind, parallel-group study, the measures of treatment efficacy were the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and Clinical Global Impression Scale. The final scores for each item of the outcome measures employed were based on the consensus of at least two trained raters who were present during each rating interview. In the 13 subjects evaluated, although the D-cycloserine was well tolerated, neither dose seemed to possess adjuvant therapeutic efficacy. However, since another recent report of nine patients with schizophrenia treated for 2 weeks with a slightly higher dose of D-cycloserine (50 mg/day) described significant clinical and neuropsychological improvement, further study of the adjuvant potential of slightly higher doses of D-cycloserine seems warranted. Additionally, there might be a therapeutic window for D-cycloserine dosing, as daily doses of 250 mg have been associated with symptom worsening.", "The authors investigated the clinical effects of D-cycloserine when added to treatment with conventional neuroleptics, olanzapine, or risperidone for treatment-resistant schizophrenia.\n Twenty-four patients participated in a double-blind, placebo-controlled, 6-week crossover trial with D-cycloserine, 50 mg/day, added to their fixed dose of antipsychotic medication. Clinical ratings were performed every 2 weeks.\n D-Cycloserine treatment was well tolerated and resulted in a significant reduction in negative symptoms (mean=15%). The degree of improvement did not differ between patients treated with conventional neuroleptics and those treated with olanzapine or risperidone.\n These data support the efficacy of the addition of 50 mg/day of D-cycloserine to treatment with conventional neuroleptics and suggest that therapeutic benefits may also be attained when D-cycloserine is added to olanzapine or risperidone.", "The purpose of this study was to evaluate the effects of high-dose oral glycine on positive and negative symptoms and cognitive function when added to clozapine in adults with schizophrenia.\n The authors conducted a double-blind, placebo-controlled, parallel-group trial of 60 g/day of glycine added to clozapine for 8 weeks in 30 adults with schizophrenia. Clinical ratings were performed every 2 weeks.\n Twenty-seven patients completed the trial. Glycine augmentation of clozapine produced no statistically significant change in positive or negative symptoms or cognitive functioning. No subjects showed clinically significant worsening of clinical ratings.\n These data, combined with data from previous trials with D-cycloserine and glycine, suggest that agonists at the glycine site may be less effective when combined with clozapine than they are when combined with conventional antipsychotics.", "Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia.\n Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-serine (30 mg/kg/day), which was added to their stable antipsychotic regimens. Of these, 28 completed the trial. Measures of clinical efficacy, side effects, and serum levels of amino acids and D-serine were determined every other week. Wisconsin Card Sorting Test (WCST) was performed at the beginning and end of the trial.\n Patients who received D-serine treatment revealed significant improvements in their positive, negative, and cognitive symptoms as well as some performance in WCST. D-serine levels at week 4 and 6 significantly predicted the improvements. D-serine was well tolerated and no significant side effects were noted.\n The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia. Given the effects of D-serine on positive symptoms, a trial of D-serine alone in schizophrenia should be considered.", "Phencyclidine induces a psychotomimetic state by blocking neurotransmission at N-methyl-D-aspartic acid (NMDA) receptors. In a double-blind, placebo-controlled fashion, 14 medicated patients with chronic schizophrenia were treated with glycine, a potentiator of NMDA-receptor-mediated neurotransmission. Significant improvement in negative symptoms occurred in the group given glycine but not in the group given placebo, suggesting that potentiation of NMDA-receptor-mediated neurotransmission may represent an effective treatment for neuroleptic-resistant negative symptoms in schizophrenia.", "D-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor, has previously been shown to improve negative symptoms when added to conventional antipsychotics and, in one preliminary dose-finding study, worsened negative symptoms when added to clozapine.\n Seventeen schizophrenia outpatients treated with clozapine were assigned in random order to 6-week trials of D-cycloserine 50 mg/day and placebo in a crossover design separated by a 1 week placebo washout.\n Eleven patients competed the 13-week study. D-Cycloserine significantly worsened ratings of negative symptoms compared to placebo but did not significantly affect ratings of psychotic symptoms.\n The differing effects of D-cycloserine on negative symptoms when added to clozapine compared to conventional antipsychotics suggests that activation of the glycine recognition site may play a role in clozapine's efficacy for negative symptoms.", "In a preliminary dose-finding study, D-cycloserine, a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d.\n Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine, 50 mg/d (n=23) or placebo (n=24) added to their conventional neuroleptic for an 8-week, double-blind trial. Clinical assessments were performed at baseline and at weeks 1, 2, 4, 6, and 8. Serum concentrations of D-cycloserine, relevant amino acids, and homovanillic acid were assayed at baseline and at weeks 4 and 8. A cognitive battery was performed at baseline and at week 8.\n Thirty-nine patients completed the 8-week trial. Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group. The mean reduction in negative symptoms with D-cycloserine (23%) was significantly greater than with placebo (7%) as calculated by slopes representing Scale for the Assessment of Negative Symptoms (SANS) total scores. Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score. No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure. Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8.\n These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms.", "The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia.\n In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly.\n The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms.\n These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine.", "A hypofunction of the glutamatergic system and NMDA receptors in schizophrenia has been hypothesized. Therefore, stimulation of these receptors could be of benefit to patients with schizophrenia. D-cycloserine has been used for this purpose. This study reports the effects of 100 mg D-cycloserine, when added to typical antipsychotics in chronic schizophrenic patients exhibiting prominent negative symptoms, using a placebo-controlled, double-blind, parallel, design. D-cycloserine slightly worsened psychotic symptoms and general psychopathology as compared to placebo. D-cycloserine failed to change negative symptoms and had no effect on extrapyramidal symptoms. The exacerbation of schizophrenic symptoms may be explained by the antagonistic effects of this dose of D-cycloserine at the glycine recognition site of the NMDA receptor due to competition with the endogenous agonist glycine. Another explanation for the increase in psychopathology may be an interaction with the effects of antipsychotics on NMDA mediated neurotransmission. Thus, D-cycloserine in this study did not ameliorate schizophrenic symptoms. However, the fact that they actually worsened suggests that NMDA systems may be involved in the pathogenesis of schizophrenia. Further placebo-controlled studies with lower dosages of D-cycloserine, preferably in drug-free patients, are necessary to evaluate if D-cycloserine is of use for the treatment of patients with schizophrenia.", "D-Serine is a full agonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive, negative, and cognitive symptoms, whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients. To study the difference between full and partial agonists at the NMDA receptor glycine site, the clinical effects of adding D-serine to clozapine were assessed.\n In a 6-week double-blind trial, 20 schizophrenic patients received placebo or D-serine (30 mg/kg per day) in addition to clozapine. Clinical efficacy, side effects, and serum levels of D-serine were determined every other week.\n The patients exhibited no improvement with D-serine, nor did their symptoms worsen, as previously reported with D-cycloserine.\n The results suggest either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to D-serine.", "Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.", "CX516, a positive modulator of the glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, improves performance in tasks requiring learning and memory in animals. CX516 was added to clozapine in 4-week, placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516 was tolerated well and was associated with moderate to large, between-group effect sizes compared with placebo, representing improvement in measures of attention and memory. These preliminary results suggest that CX516 and other \"ampakines\" hold promise for the treatment of schizophrenia." ]

[ "19935020", "6349925", "10836195", "20185226", "393049", "3299858", "2289388", "9988834", "12268918", "10715366", "12317444", "11672549", "8334888", "2495891", "10382078", "10561675", "2352250", "10427482" ]

[ "Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.", "Comparison of contraceptive acceptability of levonorgestrel and ethinyl oestradiol administered in one three-phasic (Trionetta) and one monophasic (Neovletta) version.", "A comparison of cycle control and effect on well-being of monophasic gestodene-, triphasic gestodene- and monophasic desogestrel-containing oral contraceptives. Gestodene Study Group.", "A comparison between monophasic levonorgestrel-ethinyl estradiol 150/30 and triphasic levonorgestrel-ethinyl estradiol 50-75-125/30-40-30 contraceptive pills for side effects and patient satisfaction: a study in Iran.", "Fertility regulation using \"triphasic\" administration of ethinyl estradiol and levonorgestrel in comparison with the 30 plus 150 micrograms fixed dose regime.", "[Triphasic versus monophasic p-pill. A comparative multicenter study].", "Cycle control on low-dose oral contraceptives: a comparative trial.", "\"Estrophasic\" dosing: A new concept in oral contraceptive therapy.", "[A comparative clinical study of the effects of three types of low-dose estrogen/progestogen oral contraceptives].", "Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 micrograms and 35 micrograms estrogen preparations.", "A randomised comparative study of Triquilar versus Marvelon: the Malaysian experience.", "Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.", "A multicenter comparative trial of triphasic and monophasic, low-dose combined oral contraceptives.", "A comparative analysis of three different dose combinations of oral contraceptives.", "Clinical comparison of triphasic norgestimate/35 micrograms ethinyl estradiol and monophasic norethindrone acetate/20 micrograms ethinyl estradiol. Cycle control, lipid effects, and user satisfaction.", "A multicenter randomized comparison of cycle control and laboratory findings with oral contraceptive agents containing 100 microg levonorgestrel with 20 microg ethinyl estradiol or triphasic norethindrone with ethinyl estradiol.", "Initial selection of oral contraceptives.", "A comparison of cycle control with monophasic levonorgestrel/ethinylestradiol 100 micrograms/20 micrograms versus triphasic norethindrone/ethinylestradiol 500-750-1000 micrograms/35 micrograms: a multicenter, randomized, open-label study." ]

[ "To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol (E2) 25-microgram oral contraceptive pill (OCP) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP.\n In a three-cycle, open-label, multicenter study, healthy, sexually active women were assigned randomly to a 21/7-day (norgestimate/ethinyl E2) or 24/4-day (drospirenone/ethinyl E2) OCP regimen. Randomization was stratified to assure a balanced distribution between regimens for \"fresh starts\" and \"switchers.\" Bleeding data were collected daily using an interactive voice-response system. Bleeding was defined according to the 2007 U.S. Food and Drug Administration's Reproductive Health Drug Advisory Committee-endorsed criteria.\n Across the three cycles, the 21/7-day OCP group (n=165) reported fewer unscheduled bleeding days than did the 24/4-day OCP group (n=167) (mean 4.6 compared with 6.1 days, P=.003). Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP (mean 1.47 compared with 2.01, P=.001). Moreover, women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle (P<.001). Both regimens were well-tolerated.\n A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen.\n ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00745901.\n I.", "In a Swedish multicenter study, a total number of 835 women completed a total of 6472 treatment cycles. Half of them were allotted at random to use the monophasic oral contraceptive Neovletta, also known as Microgynon 30 (30 micrograms ethinyl oestradiol + 150 micrograms levonorgestrel in each tablet). The second half was allotted to Trionetta, also known as Triquilar, Trigynon and Logynon (6 tablets with 30 micrograms ethinyl oestradiol + 50 micrograms levonorgestrel, 5 tablets with 40 micrograms ethinyl oestradiol + 75 micrograms levonorgestrel and 10 tablets with 30 micrograms ethinyl oestradiol + 125 micrograms levonorgestrel). The latter version was also present in a 28-day version containing in addition 7 \"placebo\" tablets to be used in the otherwise tablet-free interval. The contraceptive reliability was excellent although one pregnancy occurred in the three-phase version. It could be attributed to patient failure. In all aspects of bleeding control, the three-phasic pill proved to be superior to the reference monophasic preparation. The extreme low incidence of missed withdrawal bleeding and stability already during the first months of use are noteworthy features. For both preparations, continuation rate was at six months of use about 85% and at 12 months it was a similar figure. The most common reason for withdrawal was bleeding, about 5% each for both preparation. No serious side-effects were reported. The study clearly indicates that the three-phasic version is a major improvement in spite of a considerably decreased total dose of the gestagen.", "This was an open-label multicenter study to compare the cycle control and effect on well-being of two oral contraceptives containing gestodene and one containing desogestrel. A total of 2419 healthy women < or = 41 years of age were randomized to receive oral contraceptives containing monophasic gestodene (Minulet; n = 806, mean age 24.5 years), triphasic gestodene (Tri-Minulet; n = 808, mean age 24.6 years) or monophasic desogestrel (Mercilon; n = 805, mean age 24.6 years). Subjects were to participate in the study for up to 13 treatment cycles. A modified Moos Menstrual Distress Questionnaire was used to evaluate menstrual symptoms and to assess overall well-being. A total of 698 women were withdrawn from the study, 154 due to adverse events. Cycle control with gestodene was superior to that with desogestrel at almost all time points, particularly for breakthrough bleeding and/or spotting, which occurred significantly less frequently with gestodene than with desogestrel at cycles 1-7 and 9-11 (p < 0.05). Generally, the proportion of subjects with breakthrough bleeding and/or spotting was almost twice as great with desogestrel as with gestodene. The duration of bleeding was not consistently different between the gestodene and desogestrel groups; however, the intensity of bleeding was greater with gestodene at all time points (p < 0.05). The latent period before withdrawal bleeding was significantly longer for monophasic gestodene at cycles 1-5 and 8-10 (p < 0.05). Treatment significantly improved overall well-being at cycles 6 and 9 with triphasic gestodene and at cycle 13 with desogestrel; however, no statistically significant differences among treatment groups in overall well-being scores or individual factors of well-being could be identified. All three treatments were well tolerated. The most common drug-related adverse events were headache (14.2%), breast pain (6.2%), nausea (4.1%), metrorrhagia (3.9%) and abdominal pain (3.5%). The incidence of adverse events in all treatment groups was similar, with the exception of metrorrhagia, which occurred in more patients in the desogestrel group than in the gestodene treatment groups (p < 0.05).", "Oral contraceptive pills (OCPs) are one of the most effective reversible and accessible contraceptives, and patient acceptance for their use depends partly on the unfavorable adverse effects. The present study compared the two kinds of OCPs (monophasic; levonorgestrel (LNG)-ethinyl estradiol (EE) 150/30 versus triphasic; LNG-EE 50-75-125/30-40-30) for adverse effects and patient satisfaction.\n A randomized clinical trial was performed on 314 women who used OCPs for the first time, as their contraception, for 6 months. Overall, 1884 cycles were studied. In the monophasic group (n=159 who finally finished the study), monophasic pills LNG-EE 150/30mcg, and in the triphasic group (n=155 who finally finished the study), triphasic pills LNG-EE 50-75-125/30-40-30 mcg were used. Statistical analysis was performed using SPSS 10: Chi square test, Fisher exact test and Student's t-test were used.\n There were no significant differences between the two groups for common side effects, including nausea, headache, nervousness, facial hyperpigmentation (chloasma), and body weight (increase or decrease) but breakthrough bleeding and spotting (BTB/S) were less in the triphasic group, occurring in 30 cycles (18.86%) versus 10 cycles (6.45%), P=0.009*. Patient satisfaction for the two OCPs was similar and high. The rates of side effects were low.\n It seems that the monophasic and triphasic pills are similar according to patient satisfaction and side effects; therefore there is no benefit of one over the other except for BTB/S, for which triphasic is superior.\n Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.", "nan", "nan", "Cycle control was studied comparing the monophasic oral contraceptive Loestrin with three low-dose phasic preparations (Triphasil, Ortho 10/11 and Ortho 7/7/7) in 391 women of whom 300 completed 6 cycles. Loestrin subjects had a rate of occurrence (31% of cycles) for intermenstrual bleeding (IMB) comparable to the rates for subjects on the phasic preparations (36%, 37% and 37%, respectively). Triphasil subjects had lower rates than the Ortho 10/11 and Ortho 7/7/7 subjects (p less than 0.01) in cycle one when all subjects were analyzed and in pre-study users when continuing menstrual flow (CMF) episodes were not included as IMB. IMB was a cause for dropping out of the study in 7% of subjects who were evenly distributed between groups. There were no differences between groups for BTB when perceived by subjects as a side effect. Spotting was perceived as a side effect more often with Ortho 10/11 and Ortho 7/7/7 use than with Triphasil (p less than 0.01). Loestrin, Ortho 10/11 and Ortho 7/7/7 subjects were more likely to report amenorrhea (p less than 0.001) and less likely to report leg cramps (p less than 0.01) compared to those on Triphasil. Triphasil subjects were less likely to report acne than subjects on Ortho 7/7/7 (p less than 0.01).", "The first of a new \"estrophasic\" type of oral contraceptive with 20 microg ethinyl estradiol on cycle days 1 through 5, 30 microg ethinyl estradiol on days 6 through 12, and 35 microg ethinyl estradiol on days 13 through 21 and 1 mg norethindrone acetate throughout the cycle (Estrostep; Parke-Davis, Morris Plains, NJ) combines a continuous low progestin dose with a low, gradually increasing estrogen dose. It was developed to ensure good cycle control while conferring the benefits of low hormone content, such as minimizing estrogen-related side effects. In a double-blind, randomized, parallel-group trial, Estrostep provided acceptable cycle control and excellent tolerableness, comparable to that of the 30-microg ethinyl estradiol monophasic control drug. In a second study Estrostep demonstrated a neutral impact on serum lipids, like the triphasic control drug. This new oral contraceptive design offers a useful low-dose alternative to existing combination preparations.", "nan", "Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 micrograms preparations are available. To address this issue, we conducted a randomized, open-label multicenter clinical trial comparing Alesse (20 micrograms ethinyl estradiol [EE]), Mircette (20 micrograms EE), and Ortho Tri-Cyclen (35 micrograms EE) among 463 OC starters or switchers. Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 micrograms EE as compared to 20 micrograms EE preparations. Cycle control was similar in all products, although during the first two cycles among starters; users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 micrograms EE users.", "nan", "This multicenter study compared the contraceptive efficacy, cycle control, and safety of a new triphasic norgestimate (180/215/250 microg)/ethinyl estradiol 25 microg regimen (Ortho Tri-Cyclen Lo) (n = 1,723) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg (Loestrin Fe 1/20) (n = 1,171). Healthy women were treated for up to 13 cycles. Demographics were similar between regimens. Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20. The overall and method failure probabilities of pregnancy through 13 cycles were 1.9% and 1.5%, respectively, with Ortho Tri-Cyclen Lo and 2.6% and 2.4%, respectively, with Loestrin Fe 1/20. Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group. At representative Cycles 1, 3, 6, 9, and 13, breakthrough bleeding and spotting rates were 16.3, 11.5, 10.3, 7.9, and 7.7%, respectively, in the Ortho Tri-Cyclen Lo group and 34.9, 22.9, 22.2, 15.9, and 13.1%, respectively, in the Loestrin Fe 1/20 group. Compliance and safety data were similar for the two regimens.", "A comparative multicenter clinical trial of two combined oral contraceptives (OCs) was conducted at clinics located in the Sudan, Sri Lanka, Chile, the Dominican Republic and Ecuador. The trial was designed to determine if there were differences in efficacy, safety and acceptability between a triphasic and a low-dose monophasic OC. This report includes analysis of 1088 women. At each center, subjects were randomly allocated to one of the two OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. There were two accidental pregnancies attributed to user failure reported during the study period; one in the triphasic group and one in the monophasic group. Adverse experiences were mainly minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding. Both OCs were safe and effective.", "Three different low-dose formulations of oral contraceptives were compared to determine the most suitable preparation for Filipino women as reflected in the first year continuation rates, incidence of side effects and failure rates. A total of 1,800 subjects were enrolled in the study from 18 health centers in six provinces in two regions of the Philippines, covering a total of 18,282 women-months of use. Sociodemographic characteristics were comparable. The monophasic levonorgestrel group showed the best performance followed by the triphasic preparation. The norethindrone group consistently showed higher drop-out rates, which may be due to the relatively higher incidence of side effects. For all three preparations, bleeding irregularities were low. There were no major side effects and no pregnancy was reported in one year of use. Noted was a distinct regional and provincial difference in recruitment and follow-up performance, possibly due to clinic, client or program factors.", "This six-cycle, multicenter, open-label, randomized study compared the clinical experience of two low-dose oral contraceptives (OC): a triphasic OC containing norgestimate (NGM) and 35 micrograms ethinyl estradiol (EE) (Ortho Tri-Cyclen) and a monophasic OC containing norethindrone acetate (NETA) and 20 micrograms EE (Loestrin Fe 1/20). Cycle control, lipid and androgen profiles, and user satisfaction were studied in new-start OC users (i.e., no prior use within 60 days). Breakthrough bleeding or breakthrough spotting (BTB/BTS) occurred in a significantly smaller percentage of NGM/EE users than NETA/EE users during each of six cycles (p < or = 0.002). The incidence of BTB/BTS ranged from 3.7% to 13.5% for NGM/EE users and from 23.5% to 49.7% for NETA/EE users. Significantly fewer NGM/EE users than NETA/EE users experienced absence of menses at cycles 2 through 6 (p < or = 0.003). The percentages of women having no menses at each cycle ranged from 0.9% to 4.7% for NGM/EE users and from 10.3% to 21.3% for NETA/EE users. NGM/EE users reported a significantly (p < 0.001) higher level of satisfaction with their OC at the end of six cycles than did NETA/EE users, but there was no significant difference in compliance, discontinuation rates, or adverse events between the two groups. NGM/EE produced a significantly (p < or = 0.001) greater beneficial effect on HDL-C, HDL2, and apo A-I than did NETA/EE. No statistically significant treatment differences were found for total cholesterol, LDL-C, triglycerides, or apo-B. Both OC increased sex hormone binding globulin and decreased free testosterone, but NGM/EE had a significantly greater effect (p < 0.009).", "This study was undertaken to compare the effects of 2 oral contraceptive regimens on menstrual cycle control and laboratory findings.\n In a multicenter randomized study 100 microg levonorgestrel with 20 microg ethinyl estradiol (Alesse or Loette) was given to 155 healthy women. A triphasic preparation of 500, 750, and 1000 microg norethindrone with 35 microg ethinyl estradiol (Ortho-Novum 7/7/7 or TriNovum) was given to 167 women for 1 to 4 cycles of treatment.\n Overall, the percentages of normal menstrual cycles and the percentages of cycles with intermenstrual and withdrawal bleeding were similar between the 2 treatment groups. In the levonorgestrel with ethinyl estradiol group, there was a statistically significantly longer latent period and a statistically significantly shorter withdrawal bleeding episode. Adverse events were similar between treatment groups, and none were serious. Most mean changes from baseline laboratory values were comparable between groups, although the mean increase in cholesterol concentration was statistically significantly lower in the levonorgestrel with ethinyl estradiol group. Changes in triglyceride and glucose concentrations were not statistically significantly different between groups.\n Levonorgestrel (100 microg) with ethinyl estradiol (20 microg) provides menstrual cycle control equivalent to that obtained with triphasic norethindrone with ethinyl estradiol (75% higher estrogen dose) with similar safety and tolerability.", "A prospective, randomized trial compared client experiences with three popular oral contraceptives--Triphasil, Ortho-Novum 7/7/7 and Ortho-Novum 1/35. After one year, no significant relationship was found between the contraceptive prescribed and either breakthrough bleeding or satisfaction with the medication. The monophasic formulation, Ortho-Novum 1/35, was associated with amenorrhea more often.", "This multicenter, randomized, open-label study was undertaken to compare the effects on menstrual cycle control of two oral contraceptive regimens: monophasic levonorgestrel (LNG) 100 micrograms/ethinylestradiol (EE) 20 micrograms (Alesse or Loette) and triphasic norethindrone (NET) 500-750-1000 micrograms/EE 35 micrograms (OrthoNovum 7/7/7).\n Healthy women with normal menstrual cycles were enrolled and completed up to four cycles of study medication. A total of 384 cycles in the LNG/EE group and 400 cycles in the NET/EE group were evaluable for analysis of cycle control.\n For all treatment cycles, the percentage of cycles classified as normal was consistently higher in the LNG/EE group than in the NET/EE group. By cycle 4, 69.9% of cycles with LNG/EE and 54.4% with NET/EE (p < 0.05) were normal. In individual cycles, consistently lower occurrences of intermenstrual bleeding (total bleeding and/or spotting) were seen for the LNG/EE group, although these differences were not statistically significant. Withdrawal bleeding characteristics were comparable between the two groups, except for the length of the latent period, which was significantly longer in the LNG/EE group. The incidence of treatment-emergent adverse events was similar in the two groups.\n This study indicates that the monophasic LNG/EE 100 micrograms/20 micrograms provides better cycle control than the multiphasic NET/EE product, despite its lower EE dose." ]

[ "10325453", "11255446", "10881250", "10881251", "16083542", "15596605" ]

[ "The effects of donepezil in Alzheimer's disease - results from a multinational trial.", "Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease.", "Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group.", "A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group.", "Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period.", "Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial." ]

[ "Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.", "Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function.\n To investigate the long-term benefits of donepezil treatment in patients with AD.\n Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout).\n All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged.\n Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes.\n After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events.\n Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.", "Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD.\n A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable.\n Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity.\n Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.", "To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD.\n A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out.\n After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild.\n Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.", "Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimer's disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimer's disease over a 2-year period.\n Patients were randomly assigned to rivastigmine 3-12 mg/day or donepezil 5-10 mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs.\n In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT-LOCF population. However, this was not maintained in the non-ITT-LOCF populations. In secondary subgroup analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment.\n Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning.", "To evaluate the efficacy of donepezil in patients with early-stage Alzheimer disease.\n Multicenter, randomized, double-blind, 24-week, placebo-controlled study that enrolled patients with early-stage Alzheimer disease. Patients were randomized in an approximately 2:1 ratio to donepezil, 5 mg/d, for the first 6 weeks, with a forced escalation to 10 mg/d thereafter (n = 96), or placebo (n = 57). The primary efficacy measure was the modified Alzheimer Disease Assessment Scale-cognitive subscale. Secondary efficacy measures included the Mini-Mental State Examination, the Computerized Memory Battery Test, the Clinical Dementia Rating Scale-Sum of the Boxes, the Patient Global Assessment Scale, and the Apathy Scale.\n Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point (last observation carried forward); treatment differences were 1.9 (P = .03), 2.3 (P = .008), and 2.3 (P = .001) points, respectively. Improvements favoring donepezil on the Mini-Mental State Examination were found at weeks 6, 12, and 24 and at the end point (last observation carried forward); treatment differences were 1.4 (P = .02), 1.2 (P = .04), 1.4 (P = .03), and 1.8 (P = .002) points, respectively. Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales: facial recognition (P = .007 in the intent-to-treat population and P = .04 in the fully evaluable population), first and last name total acquisition (P = .02), and name-face association delayed recall (P = .04). Donepezil was safe and well tolerated in this population; serious adverse events occurred in similar numbers of donepezil- and placebo-treated patients.\n These data suggest significant treatment benefits of donepezil in early-stage Alzheimer disease, supporting the initiation of therapy early in the disease course to improve daily cognitive functioning." ]

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[ "Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic.", "Controlled clinical trial of adjuvant immunotherapy with BCG and neuraminidase-treated autologous tumour cells in large bowel cancer.", "Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283.", "Prophylactic portal infusion chemotherapy as adjuvant therapy for the prevention of metachronous liver metastasis in colorectal cancer.", "Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group.", "Prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with colon carcinoma: a randomized control trial.", "Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma.", "Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care's gastrointestinal cancer disease site group.", "Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study.", "Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01.", "Adjuvant therapy for stage II colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group.", "Five-year results of a randomized controlled trial of adjuvant chemotherapy for curatively resected colorectal carcinoma. The Colorectal Cancer Chemotherapy Study Group of Japan.", "Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil.", "Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators.", "Outcomes among African-Americans and Caucasians in colon cancer adjuvant therapy trials: findings from the National Surgical Adjuvant Breast and Bowel Project.", "An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer.", "Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from three randomized trials.", "Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer.", "Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much?", "Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer.", "The role of 5-fluorouracil dose in the adjuvant therapy of colorectal cancer.", "Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.", "Long-term survival following levamisole or placebo adjuvant treatment of colorectal cancer: a Western Cancer Study Group Trial.", "Five year results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer.", "Portal vein chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in 10 studies. Liver Infusion Meta-analysis Group.", "Preoperative immunostimulation by Propionibacterium granulosum KP-45 in colorectal cancer.", "Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial.", "AXIS--a suitable case for treatment. UK Coordinating Committee on Cancer Research (UKCCCR) Colorectal Cancer Subcommittee.", "Adjuvant active specific immunotherapy of stage II and stage III colon cancer with an autologous tumor cell vaccine: first randomized phase III trials show promise.", "Adjuvant chemoimmuno- and immunotherapy in Dukes' stage B2 and C colorectal carcinoma: a 7-year follow-up analysis.", "Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04)", "A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients.", "Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: A multicenter phase III trial.", "Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III.", "Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials.", "Adjuvant therapy for resectable colorectal carcinoma with fluorouracil administered by portal vein infusion. A study of the Mayo Clinic and the North Central Cancer Treatment Group.", "Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study.", "Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02.", "Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer.", "[Meta-analysis of postoperative adjuvant chemotherapy for Dukes' B colorectal carcinoma].", "An evaluation of the effectiveness and safety of razoxane when used as an adjunct to surgery in colo-rectal cancer. Report of a controlled randomised study of 603 patients.", "American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.", "Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer. Swiss Group for Clinical Cancer Research (SAKK)" ]

[ "A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a large national intergroup confirmatory trial currently in progress.", "A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.", "A randomized phase III clinical trial of adjuvant active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guérin (BCG) vaccine was conducted to determine whether surgical resection plus ASI was more beneficial than resection alone in stage II and III colon cancer patients.\n Patients (n = 412) with colon cancer (297 with stage II disease, 115 with stage III disease) were randomly allocated to an observation arm or to a treatment arm in which they received three weekly intradermal vaccine injections of 10(7) irradiated autologous tumor cells beginning approximately 4 weeks after surgery. The first two weekly injections also contained 10(7) BCG organisms. Patients were observed for determination of time to recurrence and disease-free and overall survival.\n This was a negative study in that after a 7.6-year median follow-up period, there were no statistically significant differences in clinical outcomes between the treatment arms. However, there were disease-free survival (P =.078) and overall survival (P =.12) trends in favor of ASI when treatment compliance was evaluated, ie, patients who received the intended treatment had a delayed cutaneous hypersensitivity (DCH) response to the third vaccination (induration >/=5 mm). Also, the magnitude of the DCH response correlated with improved prognosis. The 5-year survival proportion was 84.6% for those with indurations greater than 10 mm, compared with 45.0% for those with indurations less than 5 mm.\n When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits.", "The DNA ploidy and DNA indices (DI) of 414 patients with colorectal cancer were analyzed, and the incidence of patients with metachronous liver metastasis was found to be significantly higher in those with aneuploid tumors and a DI above 1.5 than in those with aneuploid tumors and a DI below 1.4, or in those with diploid tumors and a DI equal to 1.0. Next, to confirm the effectiveness of administering prophylactic portal infusion chemotherapy (PPIC) as adjuvant therapy for the prevention of metachronous liver metastasis in colorectal cancer, a randomized controlled trial of PPIC was performed on 110 consecutive patients with primary colorectal cancer who had undergone curative resection. Although the incidence of patients with metachronous liver metastasis in the two study groups was not significantly different at 3.3% in the PPIC group and 10.3% in the control group, the incidence in the patients with aneuploidy and a DI above 1.5 was significantly lower in the PPIC group than in the control group. These findings suggest that colorectal cancer with aneuploidy and a DI above 1.5 may have a strong tendency to metastasize to the liver, and that prophylactic portal infusion chemotherapy may be effective for preventing metachronous liver metastasis in such patients.", "Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.", "The liver is the most frequent site of recurrence after curative resection in patients with colon carcinoma. For liver metastasis, a high response rate can be achieved with hepatic arterial infusion (HAI) chemotherapy. In the current study, the authors administered 5-fluorouracil (5-FU) as adjuvant chemotherapy by HAI to patients with colon carcinoma without liver metastases and studied its effects on recurrence in the liver and survival.\n A total of 316 patients with preoperative Stage II or Stage III colon carcinoma (according to the 1997 revision of the International Union Against Cancer TNM staging system) were randomly assigned to receive surgery plus 3-week continuous HAI of 5-FU or surgery alone. There were 305 eligible patients, of whom the 119 patients assigned to the HAI arm actually received 5-FU. The primary endpoint was disease-free survival, whereas the secondary endpoints were overall survival and liver metastasis-free survival. Analysis was by intent to treat.\n There were no significant differences noted in morbidity between the two treatment arms. During the follow-up period (median, 59.0 months), the incidence of liver metastasis was significantly decreased in the HAI arm whereas there were no significant differences reported between the 2 arms with regard to the frequency of metastasis at other sites. In the HAI arm, the risk ratio for recurrence was 0.40 (95% confidence interval [95% CI], 0.24-0.64; P=0.0002), the risk ratio for death was 0.37 (95% CI, 0.21-0.67; P=0.0009), and the risk ratio for liver metastasis was 0.38 (95% CI, 0.22-0.66; P=0.0005). These differences were found to be significant only for patients with Stage III disease. Toxicities were mild.\n A schedule of 3-week HAI of 5-FU given as adjuvant chemotherapy to patients with Stage III colon carcinoma appeared to contribute to a significant decrease in the frequency of liver metastases and was associated with an improved survival rate.\n Copyright 2003 American Cancer Society.", "About half the patients treated with curative resection for colorectal cancer do not survive long-term. Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival. In patients with colorectal cancer, we have done a multicentre, randomised controlled trial comparing five-year survival after intraportal infusion of fluorouracil (1 g per day) plus heparin (10,000 U per day) (130 patients) or heparin alone (123) during curative resection and for 7 days thereafter, or after resection alone (145). There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study. However, patients who had stage III, Dukes' C (lymph-node-positive) tumours resected and were treated with fluorouracil plus heparin had a significant (p less than 0.03) survival advantage of about 16% compared with surgery-only controls. Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile.", "To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy?\n A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation.\n Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P =.07).\n There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.", "In a phase III study recruiting patients with stage II colon cancer the effect of adjuvant therapy with edrecolomab, a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, was compared to observation alone.\n From January 1997 until July 2000 a total of 377 patients were postoperatively stratified according to tumor stage (T3 vs. T4) and center, and randomly allocated to either treatment with edrecolomab (cohort A, n = 183) or observation (cohort B, n = 194). Patients in cohort A received a total of 900 mg edrecolomab. The study was terminated prematurely because of discontinuation of drug supply in Germany.\n 305 patients were eligible for the primary endpoint of overall survival and 282 patients for disease-free survival. After a median follow-up of 42 months overall survival and disease-free survival were not significantly different. Toxicity was mild.\n In the present study, postoperative adjuvant treatment with edrecolomab in patients with resected stage II colon cancer did not improve overall or disease-free survival.", "Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.", "Should patients with resected stage II colon cancer receive adjuvant therapy?\n To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage II colon cancer.\n Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens.\n Evidence was selected and reviewed by 2 members of the Provincial Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The recommendations resulting from this review have been approved by the GI DSG, which comprise medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this practice guideline but will do so in future guidelines development.\n There are 25 published randomized controlled trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs that provided adequate data.\n The 25 RCTs are grouped according to the type of therapy and whether the control patients received no treatment (observation) or other adjuvant therapy after resection. Because the trials usually included patients with stage II and III cancer, the complete trial results and those for a subset of patients with stage II disease were analysed. Although the overall trial results showed a survival benefit for adjuvant treatments, the benefit was not significant for stage II patients. A meta-analysis of 11 trials comparing adjuvant treatment with observation in patients with stage II cancer indicated no significant reduction in the odds ratio (OR) for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95% CI 0.35 to 1.11).\n The toxic effects of 5-fluorouracil (5-FU) with either levamisole or leucovorin, or both, were mild to moderate and consisted mostly of stomatitis, diarrhea and myelosuppression; 5% of patients required hospital admission. 5-FU plus levamisole was associated with transient neurotoxic effects in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly consisted of leukopenia and diarrhea; 1% of patients experienced bowel perforation.\n Adjuvant therapy is not recommended at this time for the routine management of patients with resected stage II colon cancer. Patients with stage II disease and high-risk factors (bowel obstruction, tumour adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar to that of patients with stage III colon cancer. For individual management, these patients should be made aware of their prognosis; treatment can be considered after the uncertainty of the value of adjuvant therapy has been explained to the patient. The enrolment of patients with high-risk stage II disease in clinical trials is encouraged. Trials comparing adjuvant therapy with observation are needed and are ethically acceptable in stage II colon cancer.", "In order to evaluate the significance of postoperative adjuvant chemotherapy for colorectal carcinoma, the Colorectal Cancer Chemotherapy Study Group, from 140 leading hospitals in Japan, conducted a prospective, randomized, controlled trial on patients who had undergone curative resections for colorectal carcinomas during the period from February 1984, to December 1985. The regimens for colon cancer were, Arm I: mitomycin C [intraoperative portal vein bolus (12 mg/m2) + postoperative, twice weekly and then three times bimonthly for six months intermittent i.v. bolus (6 mg/m2)] + 5-fluorouracil (5-FU) 200 mg/body/day p.o. for six months; Arm II: postoperative twice weekly and then three times bimonthly intermittent i.v. bolus mitomycin C (6 mg/m2) for six months + 5-FU 200 mg/body/day p.o. for six months; Arm III: surgery alone. The regimens for rectal cancer were, Arm IV: same as Arm I, with superior rectal artery infusion of the same mitomycin C dose instead of portal vein infusion; Arm V: same as Arm II; Arm VI: same as Arm III. Of 2001 collected cases, 1805 eligible cases (899 colon cancers and 906 rectal cancers) were analyzed. Significant differences in five-year survival rates were found between Arms IV and V and Arm VI [Arm IV: 70.7% (95% confidence interval (C.I.): 65.6-75.8%), P = 0.004 vs Arm V: 73.6% (68.5-78.7%), P = 0.000 vs Arm VI (control): 60.2% (54.5-65.9%)]. No significant difference in overall survival rate was found in the colon cancer patients [Arm I: 80.4% (75.7-85.1%), not significant (N.S.) vs Arm II: 82.1% (77.8-86.4%), N.S. vs Arm III (control): 79.5% (74.6-84.4%)]. When stratified into Dukes classes, however, Dukes C patients in Arm II showed a significantly improved survival rate compared with that of those in Arm III [Arm I: 72.6% (64.8-80.4%), N.S. vs Arm II: 75.0% (67.9-82.1%), P = 0.012 vs Arm III (control): 61.0% (51.4-70.6%)]. We conclude the adjuvant use of long term oral 5-FU and intermittent mitomycin C (i.v.) to improve the survival rate of patients with curatively resected rectal cancer. Further comparative study is, however, recommended to confirm the effectiveness of 5-FU alone and the combination of 5-FU and mitomycin C. Regional chemotherapy made no contribution to reducing an hepatic recurrence of colon cancer or a local recurrence of rectal cancer.", "The purpose of the present trial was to clarify the efficacy of postoperative adjuvant chemotherapy including an oral fluoropyrimidine anticancer drug, the 1-hexylcarbamoyl-5-fluorouracil (HCFU), for the treatment of colon cancer.\n Patients with clinical stage Dukes' B and C colon cancer, who had been treated surgically, were assigned to a chemotherapy group treated with mitomycin C, 5-fluorouracil (5-FU), and HCFU and to a control group that received no postoperative adjuvant chemotherapy.\n Of the 1,001 patients registered for the study, 17 (1.7%) were ineligible. The incidence of toxicity was significantly higher in the chemotherapy group than in the control group. However, there were few severe side effects and no deaths related to the treatment. Overall survival showed no significant difference between the groups. The disease-free survival or the recurrence-free intervals was significantly higher in the chemotherapy group than in the control group. The incidence of hepatic recurrence was significantly (P=0.003) lower in the chemotherapy group than in the control group.\n The results of this study demonstrated the efficacy of adjuvant chemotherapy for colon cancer, i.e., combined chemotherapy that included the 5-FU oral anticancer drug HCFU.", "The goal of this analysis was to determine whether fluorouracil (FU) and folinic acid (leucovorin, LV) is an effective adjuvant therapy for patients after potentially curative resection of colon cancer in patients with B2 tumors.\n One thousand sixteen patients with B2 colon cancer entered onto five separate trials were randomized to FU + LV or observation. A pooled analysis for event-free (EFS) and overall survival (OS) using a stratified log-rank and Cox model was performed.\n The median follow-up duration was 5.75 years. Patients receiving FU + LV did not experience a significant increase in EFS or OS. The hazards ratio at 5 years was 0.83 (90% confidence interval, 0.72 to 1.07) for EFS and 0.86 (90% confidence interval, 0.68 to 1.07) for OS. The 5-year EFS was 73% for controls and 76% for FU + LV. The 5-year OS was 80% for controls and 82% for FU + LV. Increasing age and poorly differentiated tumors were significant indicators of poor prognosis (P < .02).\n This data set does not support the routine use of FU + LV in all patients with B2 colon cancer. Longer follow-up may identify a small benefit. At present, studies in B2 colon cancer designed with a no-treatment control arm should be considered appropriate.", "African-Americans generally have lower survival rates from colon cancer than Caucasian Americans. This disparity has been attributed to many sources, including diagnosis at later disease stage and other unfavorable disease features, inadequate treatment, and socioeconomic factors. The randomized clinical trial setting ensures similarity in disease stage and a uniform treatment plan between blacks and whites. In this study, we evaluated survival and related end points for African-American and Caucasian patients with colon cancer participating in randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine whether outcomes were less favorable for African-Americans.\n The study included African-American (n = 663) or Caucasian (n = 5969) patients from five serially conducted, randomized clinical trials of the NSABP. We compared recurrence-free survival, disease-free survival (recurrence, new primary cancer, or death), and survival (death from any cause) between blacks and whites by using statistical modeling to account for differences in patient and disease characteristics between the groups. Statistical tests were two-sided.\n Dukes' stage and number of positive lymph nodes were remarkably similar between African-American and Caucasian patients in each trial. Over all trials combined, an 8% (95% confidence interval [CI] = -6% to 25%; P =.27) excess risk of colon cancer recurrence that was not statistically significant was observed for blacks. A greater disparity in survival was seen, with blacks experiencing a statistically significant 21% (95% CI = 6%-37%; P =.004) greater risk of death. Treatment efficacy appeared similar between the groups.\n While the overall survival prognosis was less favorable for African-Americans compared with Caucasians in these trials, other outcomes measured were considerably more similar than those seen in the population at large, suggesting that earlier detection and adjuvant therapy could appreciably improve colon cancer prognosis for African-Americans. Continued investigations into causes of the deficits noted are warranted.", "Oral carmofur, either as a single or in combination with other chemotherapeutic agents, has been used as adjuvant chemotherapy for curatively resected colon cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with this cancer. The objective of this study was to perform a reappraisal of randomized clinical trials conducted in this regard.\n We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of oral carmofur for curatively resected colon cancer in terms of overall survival (OS) and disease-free survival (DFS).\n We analyzed individual patient data of three randomized clinical trials, which met the predetermined inclusion criteria. These three trials had a combined total of 2152 patients, carmofur as adjuvant chemotherapy compared with surgery-alone, 5 years follow-up, intention-to-treat-based analytic strategy and similar end points (OS and DFS). In a pooled analysis, 5 year OS rates were 80.4 and 76.4%, and 5 year DFS rates 76.9 and 71.0%, respectively, in carmofur and surgery-alone group. Oral carmofur had significant advantage over surgery-alone in terms of both OS [pooled hazard ratio, 0.82; 95% confidence interval (CI) = 0.68-0.99; P = 0.043] and DFS (pooled hazard ratio, 0.77; 95% CI = 0.65-0.91; P = 0.003).\n This individual patient-based meta-analysis demonstrated that oral carmofur significantly improves both OS and DFS in patients with curatively resected colon cancers.", "Adjuvant therapy of colorectal cancer with oral fluorinated pyrimidines is attractive because of its ease of administration and good tolerability. The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year.\n This meta-analysis was performed on individual data from three randomized trials conducted by the Japanese Foundation for Multidisciplinary Treatment for Cancer involving a total of 5,233 patients with stages I to III colorectal cancer.\n The overall hazard ratio in favor of oral therapy was 0.89 for survival (95% CI, 0.80 to 0.99; P =.04), and 0.85 for disease-free survival (95% CI, 0.77 to 0.93; P <.001). Thus oral therapy reduced the risk of death by 11% and the risk of recurrence or death by 15%. There was no significant heterogeneity between trials, nor did the benefit of oral therapy depend on tumor stage (I, II, or III), tumor site (rectum or colon), patient age, or patient sex.\n Oral fluoropyrimidines improve disease-free survival and survival of patients after resection of early-stage colorectal cancer. These observations support the use of these agents alone after resection of early-stage disease, as well as further testing of oral agents in combination with new drugs that have recently shown antitumor activity in advanced colorectal cancer.", "Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians. Such differences could reflect variation in access to health care, in tumor biology, or in treatment efficacy. Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians. In this study, we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large, randomized phase III trial of adjuvant chemotherapy for resected colon cancer.\n We analyzed data on 3380 patients (344 African-Americans and 3036 Caucasians) enrolled in a randomized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II (high risk) and stage III colon cancer to evaluate differences in outcomes and toxicity. We compared disease-free survival (DFS) and overall survival (OS) between African-Americans and Caucasians by the Kaplan-Meier method, computed Cox proportional hazards by multivariable analysis, and compared treatment-related toxicity rates by Fisher's exact test. All statistical tests were two-sided.\n We found no differences in DFS or OS between African-American and Caucasian patients. Five-year DFS was 57% (95% confidence interval [CI] = 52% to 62%) for African-Americans and 58% (95% CI = 56% to 60%) for Caucasians (P =.15), and 5-year OS was 65% (95% CI = 60% to 70%) for African-Americans and 66% (95% CI = 64% to 68%) for Caucasians (P =.38). On multivariable analysis, no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups (hazard ratios for African-Americans versus Caucasians: disease recurrence = 1.1, 95% CI = 0.9 to 1.3; death = 1.1, 95% CI = 0.9 to 1.3). Treatment-related toxicity differed between the African-American and Caucasian patients, with African-Americans experiencing statistically significantly lower rates of diarrhea (P<.001), nausea (P<.001), vomiting (P =.01), stomatitis (P<.001), and overall toxicity (P =.005).\n In this study of patients with similar access to health care resources and treatment with adjuvant chemotherapy, we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer. The two groups derived similar benefits from adjuvant chemotherapy. Moreover, African-Americans appeared to experience less treatment-related toxicity.", "Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain.\n Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets.\n Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients.\n Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.", "Colon cancer is one of the major health problems in industrialized countries, and its incidence appears to be increasing. Surgical resectability is the most important prognostic determinant, although despite apparently curative surgery, recurrent tumors are common. Metastatic disease cannot be cured, and thus, there is a need for better adjuvant therapies.\n Two hundred and thirty-nine patients with surgically resected colon cancer in Dukes' stage B2 or C were randomly assigned to chemotherapy or observation alone to determine whether adjuvant chemotherapy could effectively reduce the rate of cancer recurrence. One hundred and twenty-one patients in stage B2 and 118 patients in stage C were enrolled in the study. Adjuvant treatment consisted of folinic acid 200 mg/m2, intravenously, plus 5-fluorouracil 400 mg/m2, intravenously, on days 1-5 every 4 weeks for 12 cycles.\n In stage B2, no significant difference between the adjuvant arm and the observation arm was noted. In stage C, adjuvant chemotherapy produced an advantage over observation in terms of a reduction in cancer recurrence rate with prolongation of a disease-free interval (P = 0.0016) and an improvement in overall survival (P = 0.0025).\n This study shows that folinic acid plus 5-fluorouracil adjuvant chemotherapy is effective in patients with surgically resected Dukes' stage C colon carcinoma.", "In many centres, the use of 5-fluorouracil (5-FU) combined with levamisole has become standard therapy for the treatment of patients with Dukes' C colon cancer. However, the role of levamisole remains unclear.\n All of the published adjuvant studies for colorectal cancer in which 5-FU (either as a single agent or in combination with other cytotoxics or levamisole) was compared to a no-treatment control group were ranked according to the total planned dose of 5-FU (assuming a body weight of 70 kg or a body surface area of 1.7 m2) over a three-month time frame. The effect of planned total dose of adjuvant therapy on the reduction of mortality was analysed using indirect comparisons of dose on the log odds ratio of death in a linear regression analysis.\n Overall, this analysis demonstrated a significant reduction in the odds of death for those receiving 5-FU regimens compared to untreated controls (estimate 0.82, 95% CI 0.74 to 0.91, p < 0.001). This effect was larger in those receiving a larger planned dose; for a total dose of 5-FU in the first three months of greater than 10 grams, 8 to 10 grams, less than 8 grams or oral 5-FU, estimates were 0.71, 0.79, 0.93 and 1.04, respectively (p = 0.02 for trend). Similar results were observed when the planned total dose of 5-FU received over 12 months was analysed. The analysis was then repeated by separating those studies in which 5-FU and levamisole were compared to a no-treatment control. A larger effect was seen in the 5-FU/levamisole trials (odds ratio, 0.64) compared to the other 5-FU regimens (odds ratio 0.86, p = 0.04). However, when adjusted for dose, the effect of levamisole was no longer significant (p = 0.09).\n These data suggest two separate hypotheses. The first is that the benefit associated with the use of 5-FU and levamisole given as adjuvant therapy in Dukes' C colon cancer is directly related to the planned total dose of 5-FU administered. Alternatively, in view of the fact that levamisole was part of the treatment regimens in two of the three studies in which the total planned dose of 5-FU exceeded 10 grams in three months (or 40 grams in 12 months), levamisole may be critical to outcome and the 5-FU total dose or dose intensity less relevant.", "The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence, for whom the indication for such treatment is unclear.\n After apparently curative resections of colon or rectal cancer, 3239 patients (2963 [91%] with stage II [node negative] disease, 2291 [71%] with colon cancer, median age 63 [IQR 56-68] years) enrolled between May, 1994, and December, 2003, from 150 centres in 19 countries were randomly assigned to receive chemotherapy with fluorouracil and folinic acid (n=1622) or to observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil (370 mg/m2) with high-dose (175 mg) L-folinic acid or low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality. Analyses were done by intention to treat. This trial is registered with the International Clinical Trial Registry, number ISRCTN82375386.\n At the time of analysis, 61 (3.8%) patients in the chemotherapy group and 50 (3.1%) in the observation group had missing follow-up. After a median follow-up of 5.5 (range 0-10.6) years, there were 311 deaths in the chemotherapy group and 370 in the observation group; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 (95% CI 0.70-0.95; p=0.008). There were 293 recurrences in the chemotherapy group and 359 in the observation group; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 (0.67-0.91; p=0.001). Treatment efficacy did not differ significantly by tumour site, stage, sex, age, or chemotherapy schedule. Eight (0.5%) patients in the chemotherapy group and four (0.25%) in the observation group died from non-colorectal cancer causes within 30 weeks of randomisation; only one of these deaths was deemed to be possibly chemotherapy related.\n Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer, although the absolute improvements are small: assuming 5-year mortality without chemotherapy is 20%, the relative risk of death seen here translates into an absolute improvement in survival of 3.6% (95% CI 1.0-6.0).", "In 1976, the Western Cancer Study Group initiated a prospectively randomized, double-blind trial of an 18-month adjuvant program comparing levamisole with placebo treatment following surgical resection in patients with colorectal adenocarcinoma. After stratification for site of disease (colon vs. rectum) and stage (B vs. C), 78 patients were entered. The levamisole schedule was 2.5 mg/kg/day given on days 1 and 2 of each week. The median follow-up of entered patients is now 7.5 years. Toxic effects of treatment were minimal. However, no long-term survival advantage was associated with levamisole compared to placebo administration in this population with resected large-bowel adenocarcinoma.", "Following curative surgery for colorectal cancer 141 patients were randomized to receive a 6 month course of 5-fluorouracil (5FU) with or without postoperative levamisole or supportive treatment only. The patients have been followed up for a minimum of 5 years and 52 per cent of patients in the control group, 44 per cent of the 5FU group and 32 per cent of the 5FU/levamisole group have died of tumour recurrence. This represents a significant survival advantage in the patients receiving levamisole, even when other patient and tumour factors are allowed for.", "Systemic delivery of cytotoxic drugs yields relatively low doses in the liver, a major site of recurrence for colorectal cancer. Giving chemotherapy by means of continuous portal vein infusion (PVI) into the liver during the immediate postoperative period may improve therapeutic efficacy.\n We undertook a meta-analysis to assess the effects on recurrence and survival of administering fluorouracil (5-FU)-based chemotherapy by PVI after colorectal cancer surgery.\n Data on mortality and recurrence were sought for all patients enrolled in randomized trials initiated before 1987 in which a few days (range, 5-7 days) of continuous postoperative PVI of cytotoxic drugs was compared with no further treatment. Data from 10 trials (a promising initial study and nine hypothesis-testing trials) involving about 4000 patients were available for analysis. The main cytotoxic drug in each trial was 5-FU (given with heparin); however, mitomycin C was co-administered in two of the trials. Four trials included an additional control group of patients treated with continuous noncytotoxic PVI of either heparin or urokinase alone; one trial included a second control group of patients treated with continuous systemic infusion of 5-FU. Reported P values are two-sided.\n Among the 3499 patients randomly assigned to receive either cytotoxic PVI or no further treatment, 1557 deaths are known to have occurred. Survival with and without PVI appeared to be the same for the first 2 years; thereafter, it diverged significantly, with the absolute survival difference (i.e., improvement) associated with PVI at 5 years being 4.7 % (standard deviation [SD] = 1.2 %) (P = .006). When just the nine hypothesis-testing trials were considered, the absolute survival difference was 3.6% (SD = 1.2%) (P = .04). If, ignoring any potential for bias in stage assignment, attention was restricted to patients with Dukes' stage A, B, or C disease (88.3% of the total), the absolute effect on 5-year survival for all 10 trials increased to 6.0% (SD = 1.8%) (P = .001); this estimate remained statistically significant when the initial study was excluded (absolute survival difference = 4.8%; SD = 1.8%; P = .01). In contrast to the highly significant reduction in liver metastases seen in the initial study (79% reduction; SD = 15%; P = .00000007), the reduction found in the nine hypothesis-testing trials was not significant (14% reduction; SD = 10%; P = .2). In the trials with additional control groups, survival appeared to be better with cytotoxic PVI than with noncytotoxic PVI or with systemic cytotoxic drug infusion.\n PVI of 5-FU (with or without other cytotoxic drugs) for about 1 week after surgery in patients with colorectal cancer may produce an absolute improvement in 5-year survival of a few percent. Although encouraging, this finding is not statistically secure, and additional evidence from randomized trials involving several thousand more patients is needed.", "In order to improve the perioperative resistance to the spread of cancer during operation the effect of preoperative stimulation of the immunesystem by Propionibacterium granulosum KP-45 was investigated in patients with colorectal carcinoma. In a prospective randomized trial 101 patients were allocated to either treatment (n = 51) or control (n = 50). In the treatment 10 mg of Propioni bacteria were administered intravenously between the seventh and third day prior to surgical treatment. At the time of operation 21 tumours were classified as stage I (treatment n = 12, control n = 9), 22 as stage II (treatment n = 10, control n = 2). Postoperatively wound infections requiring treatment were more prevalent in the control group (n = 4) than in the treated group (n = 0). All patients were subsequently followed up for 76 months. For stage I carcinoma the survival rates, excluding perioperative deaths, were 91% in the treated and 63% in the control group respectively. One case of tumour metastasis was seen in the control group. For stage II carcinoma the survival rate was 90% for the treated group with distant spread in 1 case and 45% in the control group where the rate of recurrence was 55%. For stages III and IV there was no statistically significant difference in survival between the treated and the control groups.", "Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer.\n In a prospective randomised trial, 254 patients with colon cancer were randomly assigned postoperative ASI or no adjuvant treatment. ASI was three weekly vaccinations starting 4 weeks after surgery, with a booster vaccination at 6 months with 10(7) irradiated autologous tumour cells. The first vaccinations contained 10(7) BCG organisms. We followed up patients for time to recurrence, and recurrence-free and overall survival. Analysis was by intention to treat.\n The 5.3 year median follow-up (range 8 months to 8 years 11 months) showed 44% (95% CI 7-66) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI (p=0.023). Overall, there were 40 recurrences in the control group and 25 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significantly longer recurrence-free period (p=0.011) and 61% (18-81) risk reduction for recurrences. Recurrence-free survival was significantly longer with ASI (42% risk reduction for recurrence or death [0-68], p=0.032) and there was a trend towards improved overall survival.\n ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer. ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer.", "nan", "We performed three multi-institutional, prospectively randomized, controlled clinical trials, assessing the therapeutic effect of post-resection adjuvant active specific immunotherapy in patients with stage II and stage III colon cancer. In each study four outcomes were considered: time-to-disease recurrence, overall survival intervals, disease-free survival intervals, and recurrence-free survival intervals using the Kaplan-Meir method for generating curves and the log-rank test used to compare efficacy distributions. In addition, a meta-analysis of the three phase III trials was performed since the trials had proven homogeneity. Two main analyses were performed: (1) the intent-to-treat colon cancer patients from all three studies; and (2) analyzable colon cancer patients in all three studies. The conclusion of these analyses is that adjuvant active specific immunotherapy provided significant clinical benefits in patients with stage II colon cancer and appears to be an important new adjuvant treatment for these patients.", "A prospectively randomised controlled clinical trial of adjuvant therapy was undertaken, at a single-centre, population-based cancer institute, in patients with Dukes' stages B2 and C colorectal carcinoma after curative surgery. Between 1976 and 1983, 253 patients were randomised to either control (no further therapy after surgery), immunotherapy (oral bacille Calmette-Guérin [BCG] 120 mg once a month) for 5 years or chemoimmunotherapy (oral BCG as above with methyl-cyclohexyl-chloroethyl nitrosourea [meCCNU] 130 mg/m2 on day 1 and 5-fluorouracil [5-FU] 325 mg/m2/day on days 1-5 and 375 mg/m2/day on days 36-40) repeated every 10 weeks for 8 cycles. The median follow-up of patients is now 6.95 years. Of the control, immunotherapy, and chemoimmunotherapy groups 22.35%, 39.28%, and 28.57%, respectively, have relapsed. The log-rank analysis of results shows no disease-free or overall survival advantage for patients receiving adjuvant therapy compared with the control group. Patients receiving adjuvant immunotherapy for stage B2 appear to have a significantly inferior disease-free survival compared with other groups, but their overall survival is similar. There are no significant differences in disease-free or overall survival in the three groups of patients with stage C tumour. Of 82 patients dying, 78.05% died of progressive colorectal carcinoma, 13 patients developed a second malignancy; the remainder died of seemingly unrelated causes.", "Although the benefit from adjuvant chemotherapy has been clearly established in patients with Dukes' C colon cancer, such benefit has been questioned in patients with Dukes' B disease. To determine whether patients with Dukes' B disease benefit from adjuvant chemotherapy and to evaluate the magnitude of the benefit, compared with that observed in Dukes' C patients, we examined the relative efficacy of adjuvant chemotherapy according to Dukes' stage in four sequential National Surgical Adjuvant Breast and Bowel Project trials (C-01, C-02, C-03, and C-04) that compared different adjuvant chemotherapy regimens with each other or with no adjuvant treatment.\n The four trials included Dukes' B and C patients and were conducted between 1977 and 1990. The eligibility criteria and follow-up requirements were similar for all four trials. Protocol C-01 compared adjuvant semustine, vincristine, and fluorouracil (5-FU) (MOF regimen) with operation alone. Protocol C-02 compared the perioperative administration of a portal venous infusion of 5-FU with operation alone. Protocol C-03 compared adjuvant 5-FU and leucovorin (LV) with adjuvant MOF. Protocol C-04 compared adjuvant 5-FU and LV with 5-FU and levamisole (LEV) and with the combination of 5-FU, LV, and LEV.\n Forty-one percent of the patients included in these four trials had resected Dukes' B tumors. In all four studies, the overall, disease-free, and recurrence-free survival improvement noted for all patients was evident in both Dukes' B and Dukes' C patients. When the relative efficacy of chemotherapy was examined, there was always an observed reduction in mortality, recurrence, or disease-free survival event, irrespective of Dukes' stage, and in most instances, the reduction was as great or greater for Dukes' B patients as for Dukes' C patients. When data from all four trials were examined in a combined analysis, the mortality reduction was 30% for Dukes' B patients versus 18% for Dukes' C patients. The mortality reduction in Dukes' B patients occurred irrespective of the presence or absence of adverse prognostic factors.\n Patients with Dukes' B colon cancer benefit from adjuvant chemotherapy and should be presented with this treatment option. Regardless of the presence or absence of other clinical prognostic factors, Dukes' B patients seem to benefit from chemotherapy administration.", "Adjuvant chemotherapy is standard treatment for patients with resected colon cancer who are at high risk for recurrence, but the efficacy and toxicity of such treatment in patients more than 70 years of age are controversial.\n We performed a pooled analysis, based on the intention to treat, of individual patient data from seven phase 3 randomized trials (involving 3351 patients) in which the effects of postoperative fluorouracil plus leucovorin (five trials) or fluorouracil plus levamisole (two trials) were compared with the effects of surgery alone in patients with stage II or III colon cancer. The patients were grouped into four age categories of equal size, and analyses were repeated with 10-year age ranges (< or =50, 51 to 60, 61 to 70, and >70 years), with the same conclusions. The toxic effects measured in all trials were nausea or vomiting, diarrhea, stomatitis, and leukopenia. Patients in the fluorouracil-plus-leucovorin and fluorouracil-plus-levamisole groups were combined for the efficacy analysis but kept separate for toxicity analyses.\n Adjuvant treatment had a significant positive effect on both overall survival and time to tumor recurrence (P<0.001 for each, with hazard ratios of death and recurrence of 0.76 [95 percent confidence interval, 0.68 to 0.85] and 0.68 [95 percent confidence interval, 0.60 to 0.76], respectively). The five-year overall survival was 71 percent for those who received adjuvant therapy, as compared with 64 percent for those untreated. No significant interaction was observed between age and the efficacy of treatment. The incidence of toxic effects was not increased among the elderly (age >70 years), except for leukopenia in one study.\n Selected elderly patients with colon cancer can receive the same benefit from fluorouracil-based adjuvant therapy as their younger counterparts, without a significant increase in toxic effects.", "To evaluate the results of a prospective multicenter randomized study of adjuvant intraperitoneal 5-fluorouracil (5-FU) administered during 6 days shortly after resection of stages II and III colon cancers.\n Systemic adjuvant chemotherapy improves the survival of patients with stage III colon cancer receiving treatment for 6 months. Intraperitoneal chemotherapy theoretically combines peritoneal and hepatic effects.\n After resection, 267 patients were randomized into two groups. Patients in group 1 (n = 133) underwent resection followed by intraperitoneal administration of 5-FU (0.6 g/m2/day) for 6 days (day 4 to day 10). These patients also received intravenous 5-FU (1 g) during surgery. Patients in group 2 underwent resection alone (n = 134).\n In group 1, 103 patients received the total dose, 18 received a partial dose as a result of technical or tolerance problems, and 12 did not receive the chemotherapy. Rates of surgical death and complications were similar in both groups. Tolerance to treatment was excellent or fair in 97% of the patients and poor in 3%. After a median follow-up of 58 months, 5-year overall survival rates were 74% in group 1 and 69% in group 2; disease-free survival rates were 68% and 62%, respectively. Survival curves were superimposed until 3 years after treatment and began diverging thereafter. Among patients receiving the full treatment, the 5-year disease-free survival rate was improved in the treatment group in patients with stage II cancers but was unchanged in patients with stage III cancers.\n Chemotherapy with intraperitoneal 5-FU administered during a short period after surgery was well tolerated but was not sufficient to reduce the risk of death significantly. However, it reduced the risk of recurrence in stage II cancers. These results suggest that it should be associated with systemic chemotherapy to reduce both local and distant recurrences.", "Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (< 4 weeks) did not affect results. Compliance to 5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.", "A traditional end point for colon adjuvant clinical trials is overall survival (OS), with 5 years demonstrating adequate follow-up. A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice.\n Individual patient data were pooled from 18 randomized phase III colon cancer adjuvant clinical trials. Trials included 43 arms, with a pooled sample size of 20,898 patients. The primary hypothesis was that disease-free survival (DFS), with 3 years of follow-up, is an appropriate primary end point to replace OS with 5 years of follow-up.\n The recurrence rates for years 1 through 5 were 12%, 14%, 8%, 5%, and 3%, respectively. Median time from recurrence to death was 12 months. Eighty percent of recurrences were in the first 3 years; 91% of patients with recurrence by 3 years died before 5 years. Correlation between 3-year DFS and 5-year OS was 0.89. Comparing control versus experimental arms within each trial, the correlation between hazard ratios for DFS and OS was 0.92. Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 (92%) of 25 cases. Formal measures of surrogacy were satisfied.\n In patients treated on phase III adjuvant colon clinical trials, DFS and OS are highly correlated, both within patients and across trials. These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens, although marginally significant DFS improvements may not translate into significant OS benefits.", "We randomized 224 patients with resected Dukes' stage B2 or C colorectal cancer to either an untreated control group or to a group receiving 7 days of fluorouracil therapy (500 mg/m2 per day) by portal vein infusion. Randomization was accomplished during surgery after staging by frozen section. Only 5 (2.2%) of our 224 patients were ineligible, but an additional 10 patients assigned to portal vein infusion could not be treated because of technical problems with catheter placement. Toxic reactions were mild. There was only 1 postoperative death on each study arm. At present, the median follow-up for all patients is 5.5 years (range, 1.5 to 9.5 years). Interval to progression and survival curves essentially overlap. The same lack of treatment effect is seen in both the stage B and C subsets.", "The Southwest Oncology Group (SWOG) colorectal adjuvant study 7510 went through two phases. From 1975 to 1977, 309 patients were randomized to chemotherapy alone or the same chemotherapy plus immunotherapy. From 1977 until 1980, 317 patients were randomized among the same two therapy programs and a control group. With a minimum follow-up in either phase of greater than 7 years, data are now mature. They show no difference in relapse-free survival (RFS) nor overall survival (OS) in either the two-way phase or in the three-way phase. There is no indication, except possibly in one very small subset, that the addition of immunotherapy to chemotherapy provides an improvement in OS or in RFS. Using data from patients accrued after randomization to the control group, we fail to find evidence that either chemotherapy alone or chemoimmunotherapy improves OS or RFS when contrasted to outcomes obtained by patients on the control arm. In fact, we have significant evidence, at the P = .016 level, that chemotherapy does not improve OS by at least 50%; we also have significant evidence, at the P = .011 level, that chemoimmunotherapy will not improve OS by at least 25%. No evidence of efficacy was demonstrated for either treatment regimen, even though enough therapy was given to result in significant toxicities. Acute toxicity was at least moderate, but not fatal, in 75% of patients. Recognizable delayed toxicity included rare cases of fatal renal failure and acute leukemia.", "Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.", "To determine the effectiveness of fluorouracil plus levamisole administered postoperatively to patients with resected stage II (Dukes' B2) colon cancer.\n This randomized controlled clinical trial (INT-0035) was performed by National Cancer Institute-sponsored cancer clinical trials cooperative groups. Patients were assigned to observation only or to fluorouracil (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side effects were assessed.\n Three hundred eighteen eligible patients were analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole reduced the recurrence rate by 31%, although this trend was not statistically significant (P = .10). A total of 87 patients died: 43 on observation and 44 on fluorouracil plus levamisole. Disparity between effects on recurrence rate and overall survival is partially explained by a higher rate of non-colon cancer-related deaths on fluorouracil plus levamisole (15 v seven) and by the effects of salvage surgery with curative intent. Of seven patients with recurrence who were rendered disease-free by salvage surgery, six were on the observation arm. As was observed in patients treated with fluorouracil plus levamisole for stage III disease, toxicity was acceptable and compliance was excellent.\n Fluorouracil plus levamisole is tolerable and accepted as standard surgical adjuvant therapy for patients with stage III colon cancer, but the data from this study in stage II patients suggest a decreased relapse rate without a significant improvement in survival.", "The necessity of adjuvant chemotherapy after radical surgery for patients with Dukes' B (stage II) colorectal carcinoma remains controversial. This study was to evaluate effect of postoperative adjuvant chemotherapy on survival of Dukes' B patients with meta-analysis.\n The results of literatures on postoperative adjuvant chemotherapy for Dukes' B patients from 1985 to 2003 were analyzed synthetically.The 5-year survival rates of postoperative adjuvant chemotherapy group and surgery alone group were compared.\n Eight published randomized controlled trails were eligible, and had 6 518 patients totally. The 5-year mortality was lower in postoperative adjuvant chemotherapy group than in surgery alone group with odds ratio (OR) of 0.79, and 95% confidence interval (CI) of 0.7-0.9, (P<0.05).\n Postoperative adjuvant chemotherapy could improve 5-year survival rate of Dukes' B patients.", "A prospective controlled randomised trial to evaluate the effectiveness and safety of razoxane is reported. Some 603 patients with colo-rectal cancer having curative surgery entered the study, and all have been followed up for a minimum of five years. Statistical analysis showed that razoxane treatment had no effect either beneficial or adverse on the rates of recurrence or on five year survival of patients with colo-rectal cancer. It is possible that a more prolonged course of razoxane might have significantly influenced survival. The incidence of severe adverse reaction was low but it is of concern that one patient developed leukaemia. Should razoxane be considered for future use it is recommended that continuous low dose therapy be given for no longer than 12 months. No renal, hepatic, pulmonary or cardiac toxicity was noted.", "To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice.\n An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003.\n A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology.\n Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.", "The efficacy of adjuvant chemotherapy after surgery for colorectal cancer remains unproven. We have investigated the efficacy of a perioperative intraportal cytotoxic regimen in a randomised trial of 533 patients with operable colorectal carcinoma. Patients were randomly assigned either a single course of portal infusion with mitomycin (10 mg/m2, one dose) plus fluorouracil (500 mg/m2 per 24 h for 7 days) starting immediately after surgery, or no adjuvant treatment. 505 (94%) were evaluable. At median follow-up of 8 years, adjuvant therapy reduced the risk of recurrence by 21% (hazard ratio 0.79 [95% CI 0.62-1.00], p = 0.051) and the risk of death by 26% (0.74 [0.57-0.97], p = 0.026). The lower risk of relapse was observed in all subgroups based on node status or localisation of the tumour; the risk reduction was greatest in patients with tumour-involved lymph nodes (Dukes' C; 0.67 [0.45-0.99], p = 0.045) and for those with colon cancer (0.78 [0.56-1.09], p = 0.151). Most of the difference in overall and disease-free survival could be attributed to a consistent reduction of all kinds of tumour recurrences (local relapses, liver metastases, and other distant metastases) in the treated group, rather than to a reduction of liver relapses only. We conclude that part of the benefit obtained with a single course of adjuvant chemotherapy via the portal vein for patients with operable colorectal carcinoma might be due to the systemic effects of the portal chemotherapy." ]

[ "16537867", "19450268", "18411235", "9781732", "16356437" ]

[ "Clinical effects of heliox administration for acute bronchiolitis in young infants.", "Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure.", "Nasal continuous positive airway pressure with heliox versus air oxygen in infants with acute bronchiolitis: a crossover study.", "Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis.", "Noninvasive therapy with helium-oxygen for severe bronchiolitis." ]

[ "To assess the effect of heliox, a helium-oxygen mixture, on respiratory distress symptoms in young infants.\n Prospective, randomized, double-blind study.\n Pediatric ICU (PICU) of a university hospital.\n Twenty infants, all < 3 months old, admitted to the PICU with moderate-to-severe acute respiratory syncytial virus bronchiolitis.\n All infants were randomly and blindly assigned to inhale either heliox or an air-oxygen mixture (airox) for 1 h under an oxyhood.\n After 1 h, the respiratory distress score was significantly lower in the heliox group compared with the airox group (3.05 vs 5.5, p < 0.01), with a significant reduction in accessory muscles use (p < 0.05) and expiratory wheezing (p < 0.01). In contrast, inspiratory breath sounds and cyanosis did not significantly differ between groups. The ex-premature infants of the heliox group had a higher respiratory distress score at baseline compared with the term infants of this group (5.8 vs 5.2, p < 0.05) and a comparable decrease in the score at 60 min.\n In young infants, even those born prematurely, heliox breathing induced a rapid reduction in accessory muscles use and expiratory wheezing. Further studies are needed to confirm the decreased respiratory muscle work of breathing during heliox inhalation in this population.", "Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal.\n Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval.\n Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol.\n Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468).", "The purpose of this work was to evaluate the effects of administering either heliox or air oxygen in combination with nasal continuous positive airway pressure in infants with refractory bronchiolitis.\n We conducted a prospective, interventional, single-center, crossover study in a teaching hospital including infants 1 month to 2 years of age, consecutively admitted to the PICU from February 2004 to February 2005 for treatment of severe acute bronchiolitis unresponsive to therapy. Patients with a clinical score (Modified Wood's Clinical Asthma Score) of >5, arterial oxygen saturation of <92%, or transcutaneous CO(2) pressure of >50 mmHg despite supportive therapy, nebulized L-epinephrine, and heliox therapy through a nonrebreathing reservoir face mask were eligible. During the study period, 40 infants with bronchiolitis were admitted to the PICU; 12 fulfilled inclusion criteria. A predetermined balanced sequential allocation to either 30 minutes of treatment with nasal continuous positive airway pressure with heliox or to air-oxygen nasal continuous positive airway pressure was performed. Measurements were taken at baseline and after 30 minutes of each treatment.\n Baseline mean values were as follows: nasal continuous positive airway pressure of 7.2 cmH(2)O; clinical score of 7.7 points; transcutaneous CO(2) pressure of 61.6 mmHg; and arterial oxygen saturation of 88.6%, with the fraction of inspired oxygen at 35.4%. Clinical score, transcutaneous CO(2) pressure, and arterial oxygen saturation improved during the study time with both heliox-nasal continuous positive airway pressure and air-oxygen-nasal continuous positive airway pressure: after 1 hour, the clinical score fell 1.7 points, transcutaneous CO(2) pressure decreased 8.2 mmHg, and arterial oxygen saturation increased by 7.7%. Improvement in clinical score was double with heliox-nasal continuous positive airway pressure compared with the air-oxygen-nasal continuous positive airway pressure (2.12 vs 1.08 points), and the fall in the transcutaneous CO(2) pressure was greater with heliox-nasal continuous positive airway pressure compared with air-oxygen-nasal continuous positive airway pressure (9.7 vs 5.4 mm Hg). There was no difference in arterial oxygen saturation between groups. No patients required endotracheal intubation. No adverse effects attributable to either of the study interventions were detected.\n Nasal continuous positive airway pressure improves the clinical score and the CO(2) elimination of infants with refractory bronchiolitis. These positive effects are significantly enhanced when nasal continuous positive airway pressure is combined with heliox instead of air oxygen. Both techniques are noninvasive, seem safe, and may reduce the need for endotracheal intubation.", "To determine the efficacy of a helium-oxygen mixture in children admitted to the pediatric intensive care unit with acute respiratory syncytial virus (RSV) bronchiolitis.\n Randomized, double-blind, controlled, crossover study and nonrandomized, prospective study.\n A pediatric intensive care unit in a university hospital.\n Nonintubated children with signs of acute lower respiratory tract infection and a positive rapid immunoassay for RSV admitted to the pediatric intensive care unit.\n Treatment with either helium-oxygen or air-oxygen was administered in random order for 20 mins. Nonrandomized patients received helium-oxygen as initial therapy.\n Clinical Asthma Score, respiratory rate, heart rate, and pulse oximetry oxygen saturation values were recorded at baseline (before randomization) and at the end of each 20-min treatment period (helium-oxygen or air-oxygen). Nonrandomized patients were studied 20 mins into helium-oxygen delivery. Eighteen patients were studied, 13 of whom were randomized. Five children with severe bronchiolitis (Clinical Asthma Score of > or =6) were initially given helium-oxygen and scored at 20 mins. Mean Clinical Asthma Score was 3.04 (range 1 to 7.5) in the 13 randomized patients and 4.25 (range 1 to 9) in the 18 patients overall. Clinical Asthma Score decreased in the 13 randomized patients (mean 0.46, p < .05) and in the 18 patients overall (mean 1.23, p < .01) during helium-oxygen delivery. In randomized patients with Clinical Asthma Scores of <6 (n = 12), a positive correlation (rs = .72) was observed between the Clinical Asthma Score at baseline and the change in Clinical Asthma Score during helium-oxygen administration (p = .009). Respiratory rate and heart rate decreased during helium-oxygen treatment but were not statistically significant. No complications occurred during helium-oxygen delivery.\n Inhaled helium-oxygen improves the overall respiratory status of children with acute RSV lower respiratory tract infection. In patients with mild-to-moderate bronchiolitis (Clinical Asthma Scores of <6), the beneficial effects of helium-oxygen were most pronounced in children with the greatest degree of respiratory compromise.", "To determine whether noninvasive therapy using a helium-oxygen mixture reduces the use of positive-pressure ventilation in the treatment of respiratory failure caused by severe bronchiolitis.\n This was a multicenter, randomized, double-blind, placebo-controlled trial that recruited infants in 4 pediatric intensive care units (PICUs). A total of 39 nonintubated infants with severe bronchiolitis caused by respiratory syncytial virus (RSV) were randomly assigned within 8 hours of PICU admission to receive a helium-oxygen mixture (helium group) or an air-oxygen mixture (control group) through an inflatable head hood. The primary study outcome was the requirement for positive pressure mechanical ventilation. Results were compared using Fisher's exact test.\n No differences were noted between the control and helium groups with respect to age (1.0 vs 1.1 months), prematurity, or family history of asthma or smoking. Positive pressure ventilation was judged necessary for 4 of the 21 (19.0%) infants in the control group and in 4 of the 18 (22.2%) in the helium group (relative risk = 1.17; 95% confidence interval = 0.34 to 4.01).\n This study did not detect any differences between the patients in the helium group and the control group with respect to the rate of positive-pressure ventilation." ]

[ "8021330", "12017395", "15641602", "14520769", "8405018", "7923312", "16494645", "15218558", "15462686", "11862259", "10423616", "15476903" ]

[ "A placebo-controlled comparative evaluation of diclofenac dispersible versus ibuprofen in postoperative pain after third molar surgery.", "Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: a randomized, placebo-controlled clinical trial.", "[The specific cox-2 inhibitor valdecoxib provides effective analgesia after inguinal hernia surgery].", "Analgesic efficacy of low-dose diclofenac versus paracetamol and placebo in postoperative dental pain.", "The analgesic efficacy of diclofenac dispersible and ibuprofen in postoperative pain after dental extraction.", "Comparison of single-dose ibuprofen lysine, acetylsalicylic acid, and placebo for moderate-to-severe postoperative dental pain.", "Efficacy and tolerability of diclofenac potassium sachets in acute postoperative dental pain: a placebo-controlled, randomised, comparative study vs. diclofenac potassium tablets.", "Analgesic safety and efficacy of diclofenac sodium softgels on postoperative third molar extraction pain.", "A randomized controlled study comparing rofecoxib, diclofenac sodium, and placebo in post-bunionectomy pain.", "The Analgesic Interaction of Misoprostol with Nonsteroidal Anti-Inflammatory Drugs.", "Onset and duration of analgesia of diclofenac potassium in the treatment of postepisiotomy pain.", "Dose-ranging analgesic study of Prosorb diclofenac potassium in postsurgical dental pain." ]

[ "The analgesic efficacy of single oral doses of drinkable diclofenac dispersible 50 mg was compared with that of ibuprofen 400 mg and placebo in a randomized, double-blind, parallel-group trial in 257 adult patients (245 valid for efficacy) with severe postoperative pain after extraction of an impacted lower third molar. In this study, pain intensity (on a 100-mm visual analog scale) and pain relief from baseline (using a five-point verbal rating scale) were assessed serially during an observation period of 6 hours. Intake of rescue analgesic was permitted in case of insufficient therapeutic effect; however at least 1 hour should have elapsed after test drug consumption. On the main efficacy variable, namely, reduction in the pain intensity score, both diclofenac dispersible (n = 83) and ibuprofen (n = 80) were statistically significantly (P < .01) superior to placebo (n = 82) starting at 20 and 40 minutes, respectively, after drug intake. The active medications were also significantly (P < .01) better than placebo for the secondary efficacy parameters viz. summed pain relief scores over 6 hours (TOTPAR-6); frequency of remedication with a rescue analgesic in the three treatment groups (diclofenac, 24%; ibuprofen, 28%; placebo, 65%); mean time to remedication; and global evaluation. All the treatments were well tolerated. Thus assay sensitivity of this trial (ibuprofen significantly better than placebo) has been demonstrated; in addition, diclofenac as a dispersible formulation has been shown to be an effective analgesic for the treatment of post-surgical dental pain.", "Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain, with similar analgesic efficacy to ibuprofen and naproxen sodium. Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis.\n The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg, and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery.\n In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were randomized to receive a single dose of rofecoxib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg given every 8 hours), or placebo. Patients rated pain intensity, pain relief, and global assessments at prespecified times throughout the 24-hour period after initial dosing. Overall analgesic efficacy was determined by total pain relief over 8 hours (TOPAR8) and 24 hours (TOPAR24) and patient global assessments at 8 and 24 hours. Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief. Peak analgesic effect was the maximum pain relief attained during the first 8 hours. The duration of analgesic effect was determined by median time to rescue analgesia use.\n A total of 305 patients were randomized to treatment: 121 received rofecoxib, 121 received diclofenac sodium, and 63 received placebo. The baseline demographics were similar among the groups. Overall, 61.3% experienced moderate pain and 38.7% experienced severe pain; 53.1% were female; and the mean age was 23.4 years. The overall analgesic efficacy, as assessed by TOPAR8, of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg (20.5 vs 8.2) and placebo (20.5 vs 5.9). Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo. TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg (64.1 vs 25.1) and placebo (64.1 vs 19.2). At 24 hours, the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo. The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo (median times: 31 minutes, >4 hours, and >4 hours, respectively). The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium (3.2 vs 1.5) and placebo (3.2 vs 1.1). The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium (median times: >24 hours vs 1 hour and 37 minutes) and placebo (>24 hours vs 1 hour and 37 minutes). Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy (total pain relief and patient global assessment), but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain, osteoarthritis, and rheumatoid arthritis and did not differ significantly from placebo. Overall, both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated, although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group.\n A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours, more rapid onset of analgesia, greater maximum analgesic effect, and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery. Compared with 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg every 8 hours), a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours.", "To compare 3 oral analgesic doses--valdecoxib 20 mg, valdecoxib 40 mg and controlled-release diclofenac 75 mg--to placebo in the treatment of pain after inguinal herniorrhaphy.\n An international multicenter double-blind placebo-controlled trial comparing parallel groups receiving oral valdecoxib 20 or 40 mg, controlled-release diclofenac 75 mg, or placebo every 12 hours over a period of 36 hours. The study enrolled 269 patients undergoing inguinal herniorrhaphy with spinal anesthesia. Pain intensity difference, the sum pain intensity difference, need for rescue medication, and overall patient satisfaction were compared.\n Valdecoxib 40 mg and controlled-release diclofenac 75 mg take every 12 hours provided similar analgesia that was significantly more efficacious than placebo as shown by the sum pain intensity difference at 12 hours. Both treatments decreased pain intensity in comparison with baseline throughout the study. Differences were significant in comparison with placebo at 8-10 hours through 24 hours of administration of the first dose. No significant differences between valdecoxib 20 mg and placebo were observed. The percentage of patients needing rescue medication was significantly lower in the valdecoxib 40 mg group (30% in that group vs. 52% for placebo), and that difference was not seen for any of the other groups. All treatments were well tolerated.\n Valdecoxib 40 mg and diclofenac 75 mg provided similar quality of analgesia for treating pain after inguinal herniorrhaphy.", "To compare the efficacy and safety of diclofenac-K (12.5 mg) vs paracetamol (500 mg) and placebo given in a flexible dosage regimen to treat pain resulting from extraction of impacted third molar teeth.\n This was a 2-day, double-blind, double-dummy, randomized, parallel-group, placebo-controlled study of diclofenac-K (12.5 mg) tablets vs paracetamol (500 mg) tablets and placebo in patients with moderate or severe pain within 8 hours of extraction of impacted third molars.\n After the first 2-tablet dose, patients took on average 2.5 additional tablets of diclofenac-K or 2.4 tablets of paracetamol, almost all as 1-tablet doses. Most placebo patients discontinued by taking rescue medication (ibuprofen 200 mg) on the first day. Pain relief after the initial dose of diclofenac-K (2 x 12.5 mg) was superior to placebo (P < .01 for all efficacy outcomes) and comparable to paracetamol (2 x 500 mg). About 30% of patients in each active treatment group took rescue medication during the study, compared to 78% on placebo. About 70% in each active treatment group considered the overall pain relief to be \"some,\" \"a lot,\" or \"complete\" compared to only 15% on placebo. The incidence of adverse events in each active treatment group was low and comparable between the treatments.\n An initial double-dose of diclofenac-K (2 x 12.5 mg) or paracetamol (2 x 500 mg) adequately relieved the most intense postoperative pain, and the flexible multiple dose regimen (1 or 2 tablets) maintained adequate pain relief thereafter. Most patients needed only 1-tablet doses following the initial 2-tablet dose.", "We have compared single oral doses of drinkable diclofenac dispersible (50 mg) with ibuprofen (400 mg) and placebo in a randomized, double-blind, parallel-group trial in 127 adults complaining of at least moderately severe pain after removal of an impacted third molar. Within 40 min both diclofenac and ibuprofen produced significant pain relief that persisted for 6 h. There were no differences between diclofenac and ibuprofen in analgesic efficacy.", "In a single-dose, double-blind, parallel-group, single-site study, ibuprofen lysine 200 mg (IBL 200) was compared with acetylsalicylic acid 500 mg (ASA 500) and placebo in 183 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, duration and degree of analgesia, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, global evaluation, and requirement for additional analgesic medication; both IBL 200 and ASA 500 were significantly more effective than placebo. IBL 200 also had a significantly faster onset of action, greater peak and overall analgesic effect, and longer duration of analgesia than ASA 500. All treatments were generally well tolerated.", "This double-blind, randomised, parallel-group trial compared the analgesic efficacy of single 50 mg doses of diclofenac potassium sachets and tablets with placebo in 184 patients with moderate/severe pain after third molar extraction. The primary efficacy variable was the average pain reduction from baseline during the first 2-h postdose, using a visual analogue scale (VAS). During the first 2-h postdose, sachets and tablets significantly reduced pain (p < 0.05) vs. placebo with an incremental benefit seen for sachets over tablets (p < 0.05). Onset of analgesic effect (VAS) was at 30 min for sachets and 45 min for tablets. Pain reduction vs. placebo (VAS) was maintained for 8 h for sachets and tablets (p < 0.05). VAS-findings were confirmed by pain relief and intensity verbal scale assessments. Fewer patients re-medicated vs. placebo. No safety issues were identified. This study demonstrates that both diclofenac potassium sachets and tablets offer patients suffering from acute pain conditions an effective treatment with incremental analgesic benefits seen for sachets.", "The purpose of this single-blind, placebo-controlled, 3-arm parallel, randomized study was to compare the analgesic efficacy and tolerability of a single dose of 100 mg diclofenac potassium (Cataflam; Novartis, Stein, Switzerland), 100 mg diclofenac sodium softgel, and placebo in patients experiencing moderate to severe postoperative pain after third molar extraction.\n Seventy-five patients (67% female with a mean age of 23, age range 18 to 34.5 years) participated in the study following removal of at least 1 impacted mandibular third molar. Patients received a single dose of study medication when their postoperative pain reached a moderate or severe intensity. Analgesic efficacy measures included the time to meaningful pain relief measured using a stopwatch and time to rescue medication. Pain relief (PR) and Pain intensity (PI) ratings were recorded at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours postdosing. Summary analgesic measures, including Summed Pain Relief Score (TOTPAR) and Summed Pain Intensity Differences (SPID), were calculated from the 0.25- to 6-hour responses. The time between pain relief and rescue and a global evaluation for the effectiveness of the study medications were recorded at the end of the study. Seven scheduled blood samples were collected from each patient for determining plasma concentrations of diclofenac anion.\n Both diclofenac sodium softgel and Cataflam were significantly more effective than placebo (P <.0001) for all summary analgesic measures. The average overall pain relief was substantially better from diclofenac sodium softgel than from Cataflam, but the difference was not statistically significant (P =.14). In patients taking diclofenac sodium softgel, 50% of the patients experienced a time to onset of analgesic activity within 18 minutes and the median analgesic duration was 5 hours (302 minutes). Fifty percent of the patients taking Cataflam had a time to onset of action within 38 minutes, and the median duration of analgesia was 4.5 hours (272 minutes). At the time of rescue drug administration or 6 hours, whichever was earlier, 72% of the patients given diclofenac sodium softgel rated the medication as a very good or excellent pain reliever, whereas only 45% of the patients taking Cataflam gave these ratings. No serious adverse events were observed in this study. The mean concentrations of diclofenac from the diclofenac sodium softgel formulation were significantly different from the Cataflam formulation. The mean C(max) for the softgel was almost twice that of Cataflam and C(max) was reached an hour earlier, on average.\n More diclofenac anion was absorbed at a quicker rate using the formulation diclofenac sodium softgel 100 mg than Cataflam. The softgel provided a very rapid onset of analgesic activity, a prolonged analgesic duration, and an acceptable side-effect profile in the postoperative third molar surgery pain model. In an acute pain situation, the rapid absorption of nonsteroidal anti-inflammatory drugs from a formulation like the Softgel may positively affect the time of onset and duration of inflammatory pain compared with other commercially available nonsteroidal anti-inflammatory drug formulations.", "The relative efficacy of rofecoxib, diclofenac sodium, and placebo were compared in the treatment of acute pain after bunionectomy surgery.\n This was a double-blind, randomized, two-part study of 252 patients with moderate-to-severe pain the day after first metatarsal bunionectomy. Patients were treated with a single dose of rofecoxib 50 mg (N = 85), enteric-coated diclofenac sodium 100 mg (N = 85), or placebo (N = 82) on study Day 1 (Part I), and subsequently with daily rofecoxib 50 mg or placebo (diclofenac patients switched to placebo) over study Days 2-5 (Part II). Patients rated their pain at 16 time points over the first 24 h. Primary endpoint was total pain relief over 8 h (TOPAR8). Pre-specified secondary endpoints on Day 1 included onset of analgesia, peak pain relief, and duration of response. For Part II, supplemental analgesia use with rofecoxib compared to placebo was pre-specified for analysis over Days 2-5, with the focus on Days 2-3. Adverse experiences were recorded over Days 1-5.\n For TOPAR8 scores, rofecoxib 50 mg was significantly more effective than placebo (9.5 vs. 3.7, p < 0.001) and diclofenac (9.5 vs. 5.0, p < 0.001). Onset of analgesia was more rapid with rofecoxib than placebo (p = 0.003) and diclofenac (p = 0.019); proportion of patients achieving onset within 4 h with rofecoxib, diclofenac, and placebo was 46%, 27%, and 23%, respectively. Peak pain relief was greater with rofecoxib (1.8) than diclofenac (1.2, p = 0.004) and placebo (1.0, p < 0.001). Diclofenac and placebo patients required supplemental analgesia sooner than rofecoxib patients (2:03 h vs. 4:02 h, p < 0.001 and 1:41 h vs. 4:02 h, p < 0.001). Rofecoxib patients used significantly less (p < 0.001) supplemental analgesia than placebo patients over Days 2-3 (1.1 tablets/day vs. 2.1 tablets/day) and Days 2-5 (0.9 tablets/day vs. 1.8 tablets/day). No significant differences in adverse experiences between treatments were seen.\n Rofecoxib 50 mg was significantly more effective than placebo on all measures of treatment of post-bunionectomy pain. Rofecoxib 50 mg was significantly more effective than diclofenac sodium 100 mg based on Day 1 endpoints of total pain relief, onset time, and duration of response. All study medications were generally well tolerated.", "The purpose of this project was to evaluate the analgesic efficacy of misoprostol when combined with ibuprofen or diclofenac Na. Animal experiments using the inflamed rat paw formalin model suggested that misoprostol potentiates the analgesic effect of some NSAIDs (nonsteroidal anti-inflammatory drugs) including diclofenac Na but not propionic acid derivatives or opiates. The dental pain model was used to evaluate the clinical relevance of this interaction. Patients received a single oral dose of study medication following surgical removal of impacted teeth. Patients were medicated for moderate to severe postsurgical pain and then filled in an analgesic diary for a 6-h observation period. Several blood samples were taken over the observation period. In addition, microdialysis samples were taken directly from the extraction socket and were analyzed for immunoreactive prostaglandin E(2) levels. The studies were single-dose, parallel group and double-blind assays. In the first study, 70 patients received an oral dose of either placebo (n = 13), misoprostol 200 &mgr;g (n = 18), ibuprofen 200 mg (n = 19), or the combination of misoprostol + ibuprofen (n = 20). Misoprostol alone demonstrated a small analgesic effect compared to placebo. Both the ibuprofen and combination groups were substantially more effective than placebo but not different from each other. The combination group had higher ibuprofen blood levels during the first 45 min but had a lower C(max) and longer time to T(max). The second study evaluated oral doses of placebo (n = 11), misoprostol 200 &mgr;g (n = 21), diclofenac Na 50 mg (n = 18), and the combination of misoprostol + diclofenac Na (n = 20). Relative to placebo, misoprostol performance was similar to the first study. When the results of the two studies were combined, there was a small, but statistically significant, analgesic effect for misoprostol. Diclofenac Na was superior to both placebo and to misoprostol alone. The combination was the most effective treatment, and for hours 4--6 it was significantly better than diclofenac Na alone. Analysis of the blood samples showed an earlier and higher peak effect for the diclofenac Na group compared to the combination, and the combination again had a lower C(max). The microdialysis probe assays demonstrated that misoprostol depressed PGE(2) levels at the peripheral site of trauma over the first 2 h after surgery. These pilot studies used small samples, and the results only suggest trend effects. Both studies demonstrated that misoprostol 200 &mgr;g, a prostaglandin analog, does have an analgesic effect. When combined with ibuprofen, there was no potentiation of analgesia. In contrast, the combination of misoprostol + diclofenac Na demonstrated an enhanced peak effect, total effect for pain intensity difference and pain relief (sum pain intensity difference [SPID] and total pain relief [TOTPAR]), and", "A double-blind, placebo-controlled, parallel group study was performed to compare the analgesic efficacy of diclofenac potassium (25, 50, or 100 mg) with that of aspirin (650 mg), or placebo. Two hundred fifty-five inpatients with severe postepisiotomy pain were randomly assigned to receive a single oral dose of one of the four active treatments or placebo. Analgesia was assessed over an 8-hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data, as well as two global ratings of the study medication. All active treatments were effective analgesics statistically superior to placebo for many hourly and summary measures, including the global ratings. Diclofenac potassium (50 and 100 mg) was statistically significantly superior to aspirin at half-hour and for many other hourly scores from hour 3 on. The 4- and 8-hour sum of the pain intensity difference and total pain relief scores reflected the superiority of diclofenac potassium to aspirin. In addition, the 100-mg dose was significantly more efficacious than the 25-mg dose of diclofenac potassium. The probability of obtaining onset was significantly better for all active treatments than for placebo; however, the median onset times were similar for all treatments. The duration of effect, as measured by mean pain intensity difference and relief scores, was better for diclofenac potassium than aspirin, and these differences were significant for the 50- and 100-mg doses. The probability of pain returning to baseline was significantly less for the diclofenac groups than for placebo or aspirin groups. In addition, significantly fewer patients treated with diclofenac (25, 50, or 100 mg) or aspirin (650 mg) required remedication during the 8-hour study period as compared with those treated with placebo. Diclofenac potassium is an effective analgesic in the range of aspirin (650 mg) at the 25-mg dose and superior in efficacy and longer lasting than aspirin at the 50- and 100-mg doses. The onset of analgesia was similar for aspirin and diclofenac potassium.", "ProSorb diclofenac potassium (K) is a novel, liquid-filled rapid-dispersion formulation of the nonsteroidal anti-inflammatory drug diclofenac, placed into soft gelatin capsules. Its time to maximal plasma drug concentration has been shown to be approximately half, and its maximal plasma drug concentration nearly twice, that of immediate-release diclofenac K tablets.\n This study compared the analgesic dose-response relationship and tolerability of 3 doses of ProSorb diclofenac K and placebo in the treatment of pain after dental impaction surgery.\n This randomized, double-blind, double-dummy, placebo-controlled parallel-group study was conducted at 6 centers across the United States. Patients aged 18 to 65 years with moderate or severe pain after the removal of > or =1 impacted mandibular third molar were randomly assigned to receive a single dose of ProSorb diclofenac K 25, 50, or 100 mg or placebo. Pain intensity and relief were assessed up to 6 hours after dosing. Rescue treatment was allowed after 1 hour. Efficacy end points included the summed pain intensity difference over 3 and 6 hours (SPID3 and 6); total pain relief at 3 and 6 hours (TOTPAR3 and 6); median times to onset of perceptible and meaningful relief (analgesic onset) and rescue medication use (analgesic duration); and cumulative percentage of patients using rescue medication. Tolerability was assessed using vital sign measurements and spontaneous reporting of adverse events.\n A total of 265 patients (154 women, 111 men; mean age, 23.3 years) were enrolled. All 3 ProSorb diclofenac K groups showed higher SPID6 and TOTPAR6 scores and longer median times to rescue medication use than the placebo group (all, P < 0.001). For these end points, a dose-response relationship was evident between the 100-mg dose and the 25- and 50-mg doses (P < or = 0.05); the 25- and 50-mg doses were similar. In the diclofenac groups, median onset times for first perceptible (< or =22.5 min) and meaningful (< or =53.0 min) relief were significantly more rapid than placebo (P < or = 0.01). Proportions of patients requiring rescue analgesic were < or =50.8% with diclofenac compared with 79.4% with placebo. Proportions of patients assigning a global evaluation of good or better was > or =68% with diclofenac compared with 21% for placebo. Tolerability was similar across all treatment groups.\n In this study of patients treated for pain following dental impaction surgery, single doses of ProSorb diclofenac K 25, 50, and 100 mg were more efficacious than placebo with respect to reduction of pain. All 3 doses provided a rapid analgesic onset and were well tolerated." ]

[ "11677004" ]

[ "The value of muscle exercise in patients with amyotrophic lateral sclerosis." ]

[ "The role of physical activity for patients with amyotrophic lateral sclerosis (ALS) is controversial. Twenty-five ALS patients were randomized to receive a moderate daily exercise program (n=14) or not to perform any physical activity beyond their usual daily requirements (n=11). At baseline and after 3, 6, 9 and 12 months, patients were assessed by manual muscle strength testing, the Ashworth spasticity scale, ALS functional rating scale (FRS), fatigue severity scale, a visual analogue scale for musculoskeletal pain and the quality-of-life scale (SF-36). At 3 months, patients who performed regular exercise showed less deterioration on FRS and Ashworth scales, but not on other parameters. At 6 months, there was no significant difference between groups, although a trend towards less deterioration in the treated group on most scales was observed. At 9 and 12 months, there were too few patients in each group for statistical evaluation. Our results show that a regular moderate physical exercise program has a short-lived positive effect on disability in ALS patients and should be recommended." ]

[ "8737631", "351993", "8569363", "11933130", "815806", "1621440" ]

[ "Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency.", "[Evaluation of internally effective venous drugs].", "Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency.", "Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency.", "[Demonstration of the effectiveness of the horse-chestnut-seed extract in the varicose syndrome complex].", "Medical edema protection--clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind study." ]

[ "Oxerutins (O-(beta-hydroxyethyl)rutosides, HR, Venoruton) and horse chestnut extract (HCE) are active principles of first priority for the pharmacological treatment of chronic venous insufficiency (CVI). The efficacies of both compounds were shown in numerous, double-blind, randomized, placebo controlled clinical trials. Besides the direct comparison of the two compounds the aim of the study was to investigate the initial dose/maintenance dose concept for HR. 137 female, postmenopausal patients with CVI II finished the study according to protocol. Following one week placebo run-in the patients were treated either with 1000 mg/d HR, 600 mg/d HCE or 1000 mg/d for 4 weeks and than with 500 mg/d HR within the initial dose/maintainance dose concept for 12 weeks and observed for further 6 weeks. A main confirmative criterion was the volume reduction of the leg. Subjective criteria were descriptively evaluated. HR (1000 mg/d) was proven to be equivalent or better, reducing the leg volume (AUB0-18) by -5273 +/- 11418 ml.d compared to -3187 +/- 10842 ml.d under HR (1000 mg/d and 500 mg/d), and -3004 +/- 7429 ml.d under HCE-treatment. Both compounds exhibit a substantial carry-over effect. The maintenance posology of HR is able to stabilize the therapeutic obtained under initial dose conditions.", "nan", "Diseases of the venous system are widespread disorders sometimes associated with modern civilisation and are among the major concerns of social and occupational medicine. This study was carried out to compare the efficacy (oedema reduction) and safety of compression stockings class II and dried horse chestnut seed extract (HCSE, 50 mg aescin, twice daily).\n Equivalence of both therapies was examined in a novel hierarchical statistical design in 240 patients with chronic venous insufficiency. Patients were treated over a period of 12 weeks in a randomised, partially blinded, placebo-controlled, parallel study design.\n Lower leg volume of the more severely affected limb decreased on average by 43.8 mL (n = 95) with HCSE and 46.7 mL (n = 99) with compression therapy, while it increased by 9.8 mL with placebo (n = 46) after 12 weeks therapy for the intention-to-treat group (95% CI: HCSE: 21.1-66.4; compression: 30.4-63.0; placebo: 40.0-20.4). Significant oedema reductions were achieved by HCSE (p = 0.005) and compression (p = 0.002) compared to placebo, and the two therapies were shown to be equivalent (p = 0.001); in this design, however, compression could not be proven as standard with regard to oedema reduction in the statistical test procedure. Both HCSE and compression therapy were well tolerated and no serious treatment-related events were reported.\n These results indicate that compression stocking therapy and HCSE therapy are alternative therapies for the effective treatment of patients with oedema resulting from chronic venous insufficiency.", "The aim of this study was to compare the efficacy of Venostasin (horse chestnut seed extract) and Pycnogenol (French maritime pine bark extract) in the treatment of chronic venous insufficiency (CVI). In an open, controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks. The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment: circumference of the lower legs and rating of subjective symptoms (scores) of pain, cramps, night-time swelling, feeling of \"heaviness\", and reddening of the skin. In addition, blood levels of cholesterol LDL and HDL were determined before and at the end of treatment. Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms. Furthermore, Pycnogenol significantly decreased cholesterol and LDL values in the blood, whereas HDL remained unaffected. Venostasin only moderately but not significantly, reduced the circumference of the lower limbs and marginally improved symptoms. Venostasin had no influence on the determined lipid values. Both medications were equally well tolerated. In conclusion, Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI.\n Copyright 2002 John Wiley & Sons, Ltd.", "nan", "In a randomized placebo controlled parallel double blind study on 40 patients suffering from venous edema in chronic deep vein incompetence, the edema-reducing effect of horse chestnut seed extract vs. placebo, being the main test variable, was demonstrated by hydroplethysmography to be statistically significant. In addition, measurements of leg volume under aggravated conditions (edema provocation) were conducted, which yielded the same results. Additional measurements of leg circumference tendentially confirm the demonstrated clinical efficacy of verum, as is true for phlebody-namometric measurements (pressure at rest, minimum pressure, replenishment time) as well. By measuring the leg volume before and after edema provocation, it could be shown that the clinical benefit for the patient is present in all everyday situations (in movement as well as on sitting or standing). Treatment with an edema protective agent of the horse chestnut seed extract type is thus a useful adjunct to compression therapy. The tested preparation were well tolerated." ]

[ "12443589", "7648155", "11062788" ]

[ "The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.", "Influence of screening on the incidence of ruptured abdominal aortic aneurysm: 5-year results of a randomized controlled study.", "Screening for abdominal aortic aneurysm: lessons from a population-based study." ]

[ "Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms. The Multicentre Aneurysm Screening Study was designed to assess whether or not such screening is beneficial.\n A population-based sample of men (n=67800) aged 65-74 years was enrolled, and each individual randomly allocated to either receive an invitation for an abdominal ultrasound scan (invited group, n=33839) or not (control group, n=33961). Men in whom abdominal aortic aneurysms (> or =3 cm in diameter) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years. Surgery was considered on specific criteria (diameter > or =5.5 cm, expansion > or =1 cm per year, symptoms). Mortality data were obtained from the Office of National Statistics, and an intention-to-treat analysis was based on cause of death. Quality of life was assessed with four standardised scales. The primary outcome measure was mortality related to abdominal aortic aneurysm.\n 27147 of 33839 (80%) men in the invited group accepted the invitation to screening, and 1333 aneurysms were detected. There were 65 aneurysm-related deaths (absolute risk 0.19%) in the invited group, and 113 (0.33%) in the control group (risk reduction 42%, 95% CI 22-58; p=0.0002), with a 53% reduction (95% CI 30-64) in those who attended screening. 30-day mortality was 6% (24 of 414) after elective surgery for an aneurysm, and 37% (30 of 81) after emergency surgery.\n Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms.", "From family medical practices 15775 men and women aged 65-80 years were identified and randomized into two groups: one group was invited for ultrasonographic screening for abdominal aortic aneurysm (AAA), and the other acted as age- and sex-matched controls. Of the 7887 invited for screening 5394 (68.4 per cent) accepted. AAA was detected in 218 (4.0 per cent overall and 7.6 per cent of men). Aortic surgery was offered to the screened group if certain criteria were met and no patient died from rupture who was fit for operation and accepted elective treatment. The incidence of rupture was reduced by 55 per cent in men in the group invited for screening, compared with controls. The incidence of rupture in women was low in both groups.", "To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm (AAA) in men.\n A trial of ultrasound screening for AAA in a population-based random sample of men aged 65-83 years, and a cross-sectional case-control comparison of men in the same sample.\n 12,203 men who had an ultrasound examination of their abdominal aorta, and completed a questionnaire covering demographic, behavioural and medical factors.\n Prevalence of AAA, and independent associations of AAA with demographic, medical and lifestyle factors.\n Invitations to screening produced a corrected response of 70.5%. The prevalence of AAAs (> 30 mm) rose from 4.8% in men aged 65-69 years to 10.8% in those aged 80-83 years. The overall prevalence of large (> 50 mm) aneurysms was 0.69%. In a multivariate logistic model Mediterranean-born men had a 40% lower risk of AAA (> 30 mm) compared with men born in Australia (odds ratio [OR], 0.6; 95% CI, 0.4-0.8), while ex-smokers had a significantly increased risk of AAA (OR, 2.3; 95% CI, 1.9-2.8), and current smokers had even higher risks. AAA was significantly associated with established coronary and peripheral arterial disease and a waist:hip ratio greater than 0.9; men who regularly undertook vigorous exercise had a lower risk (OR, 0.8; 95% CI, 0.7-1.0).\n Ultrasound screening for AAA is acceptable to men in the likely target population. AAA shares some but not all of the risk factors for occlusive vascular disease, but the scope for primary prevention of AAA in later life is limited." ]

[ "18056488", "493897", "21670709", "1487353", "3056948", "2695009", "17174113", "17931895", "8493730", "21248213", "20234324", "1644464", "9480606", "6693466", "9180319", "21888842", "19945102", "6710092", "12729121", "21435907", "21783385", "21387176" ]

[ "Immediate mobilization compared with conventional immobilization for the impacted nonoperatively treated proximal humeral fracture. A randomized controlled trial.", "Independent exercises versus physiotherapy in nondisplaced proximal humeral fractures.", "Are polyaxially locked screws advantageous in the plate osteosynthesis of proximal humeral fractures in the elderly? A prospective randomized clinical observational study.", "Water exercise versus instruction for self-training following a shoulder fracture.", "Transcutaneous reduction and external fixation of displaced fractures of the proximal humerus. A controlled clinical trial.", "Functional results following fractures of the proximal humerus. A controlled clinical study comparing two periods of immobilization.", "Early versus late mobilization after hemiarthroplasty for proximal humeral fractures.", "Primary hemiarthroplasty in four-part fractures of the proximal humerus: randomized trial of two different implant systems.", "[Conservative treatment of subcapital humerus fractures. A comparative study of the classical Desault bandage and the new Gilchrist bandage].", "Locking intramedullary nails and locking plates in the treatment of two-part proximal humeral surgical neck fractures: a prospective randomized trial with a minimum of three years of follow-up.", "Monoaxial versus polyaxial screw insertion in angular stable plate fixation of proximal humeral fractures: radiographic analysis of a prospective randomized study.", "Electrotherapy and the management of minimally displaced fracture of the neck of the humerus.", "[Prosthetic humeral head replacement in dislocated humerus multi-fragment fracture in the elderly--an alternative to minimal osteosynthesis?].", "Four-part fractures of the neck of the humerus.", "Treatment of displaced proximal humeral fractures in elderly patients.", "[Surgical treatment for proximal humerus fracture].", "Health and cost consequences of surgical versus conservative treatment for a comminuted proximal humeral fracture in elderly patients.", "Physiotherapy after fracture of the proximal end of the humerus. Comparison between two methods.", "Rehabilitation after two-part fractures of the neck of the humerus.", "Internal fixation versus nonoperative treatment of displaced 3-part proximal humeral fractures in elderly patients: a randomized controlled trial.", "Hemiarthroplasty versus nonoperative treatment of displaced 4-part proximal humeral fractures in elderly patients: a randomized controlled trial.", "The clinical benefit of medial support screws in locking plating of proximal humerus fractures: a prospective randomized study." ]

[ "There have been few randomized controlled trials evaluating nonoperative treatment of proximal humeral fractures. To investigate shortening the period of dependence, we assessed the feasibility and efficacy of early mobilization of the shoulder (within three days after the fracture) in comparison with those of conventional three-week immobilization followed by physiotherapy.\n We randomly assigned seventy-four patients with an impacted proximal humeral fracture to receive early passive mobilization or conventional treatment. The primary outcome was the overall shoulder functional status (as measured with the Constant score) at three months. The secondary outcomes were the Constant score at six weeks and at six months, the change in pain (on a visual analog scale), and the active and passive range of motion.\n At three months and at six weeks, the early mobilization group had a significantly better Constant score than did the conventional-treatment group (between-group difference, 9.9 [95% confidence interval, 1.9 to 17.8] [p = 0.02] and 10.1 [95% confidence interval, 2.0 to 18.1] [p = 0.02], respectively) and better active mobility in forward elevation (between-group difference, 12.0 [95% confidence interval, 1.7 to 22.4] [p = 0.02] and 28.1 [95% confidence interval, 7.1 to 49.1] [p = 0.01], respectively). At three months, the early mobilization group had significantly reduced pain compared with the conventional-treatment group (between-group difference, 15.7 [95% confidence interval, 0.52 to 30.8] [p = 0.04]). No complications in displacement or nonhealing were noted.\n Early mobilization for impacted nonoperatively treated proximal humeral fractures is safe and is more effective for quickly restoring the physical capability and performance of the injured arm than is conventional immobilization followed by physiotherapy.", "42 patients with undisplaced, proximal humeral fractures were randomly assigned into two groups in order to compare the results of instruction to the patient for independent exercises and conventional physiotherapy. No differences appeared between the groups subjectively or as regards functional parameters at 1 as well as at 3 months after the fracture and at a follow up more than 1 year later. As no disadvantage could be found instructions to the patients should in these cases be regarded as a satisfactory after-treatment.", "To evaluate the results of plate osteosynthesis using either polyaxial or nonpolyaxially locked screw-plate systems in proximal humeral fractures in the elderly.\n Prospective, randomized.\n Level I trauma center.\n Fifty-six patients (older than 60 years) with isolated, displaced three- and four-part fractures were included. Twenty-five patients (median age, 75.5 years) were randomized to a polyaxial locking screw plate (Group 1), whereas 31 patients (median age, 72 years) were treated with a locking screw plate (Group 2). Follow-up evaluations were performed 3, 6, and 12 months postoperatively using the Simple Shoulder Test, Disabilities of the Arm, Shoulder and Hand score, and Constant score as well as radiographs. The results and the complications were compared between both groups.\n Forty-eight patients were available for follow-up (Group 1, 20 of 25; Group 2, 28 of 31). The Simple Shoulder Test, Disabilities of the Arm, Shoulder and Hand, and Constant score improved significantly from 3 to 12 months and did not differ between groups. Twelve months after the index procedure, the Simple Shoulder Test score was 8.6 ± 3.2 points in Group 1 and 9.7 ± 1.8 points in Group 2. The Disabilities of the Arm, Shoulder and Hand score was 17.8 ± 16.2 in Group 1 and 15.7 ± 11.8 in Group 2. The mean Constant score amounted to 73% ± 17% in Group 1 and 81% ± 13% in Group 2. There were six complications in Group 1 and eight in Group 2.\n Both the functional outcomes and the rate of complications after polyaxial locked plate osteosynthesis of proximal humeral fractures in elderly patients were comparable to those treated with nonpolyaxial implants. Despite the theoretical advantages of polyaxial locked plating in proximal humerus fractures, this study could not show a verifiable clinical advantage of these plates.", "nan", "A consecutive series of 31 displaced fractures of the proximal humerus were randomly selected for treatment either by closed manipulation or by transcutaneous reduction and external fixation. Follow-up assessed the quality of reduction and healing as well as the functional outcome. The external fixation method gave better reduction, safer healing and superior function.", "In order to compare 1 and 3 weeks of immobilization following proximal humeral fractures a prospective controlled trial was performed in 85 patients. Clinical follow-up according to the Neer assessment system was done after 1, 3, 6, 12, and 24 months. One week of immobilization resulted in a better total score due to less pain during the first 3 months. After 6 months no difference in pain, function, or mobility was found and no further recovery of shoulder function was seen after 12 and 24 months.", "This randomized controlled trial compares 2 mobilization regimens after shoulder hemiarthroplasty for acute 3- and 4-part fractures. The aim was to establish whether the length of immobilization plays a role in the functional outcome, tuberosity healing, and subsequent range of motion. The same prosthesis and surgical technique were used. We recruited 59 patients into the study; 31 were randomized to early (2 weeks) mobilization and 28 to late (6 weeks) mobilization. Greater tuberosity migration was assessed with a series of radiographs, and the functional outcome was assessed with the Constant Shoulder Assessment and Oxford shoulder scores. Of the patients, 49 (mean age, 70 years) met the inclusion criteria and were followed up for 12 months. Greater tuberosity migration occurred in 3 cases in the early mobilization group and once in the late mobilization group (P > .10). There was no significant difference in the Constant Shoulder Assessment and Oxford scores between the 2 groups. Although there was a decreased incidence of tuberosity migration in the group undergoing late mobilization, this was not statistically significant.", "The objective of this study was to determine the effect of different prosthetic systems on the functional and radiographic outcomes after shoulder arthroplasty for fractures. This study comprised 35 patients (28 women and 7 men) with a mean age of 74 years (range, 56-88 years) who sustained 4-part fractures of the proximal humerus and were randomly allocated to 2 different groups regarding the type of prosthesis. The 2 systems used differ mainly in the type of fixation of the tuberosities. In group 1 (EPOCA), the fixation was achieved with wire cables through a medial and a lateral hole in the stem, whereas in group 2 (HAS), the fixation was performed by use of transosseous braided sutures. After a follow-up of 1 year, the functional and radiographic outcomes were evaluated. The retrieved data demonstrate that rigid fixation and anatomic positioning of the tuberosities (group 1) increase the rate of bony healing superior to all other factors. There was a statistically significant difference regarding the relative individual Constant score (P = .001) and the mean active range of motion (flexion, P < .001; abduction, P = .001; external rotation in adduction, P = .01; and external rotation in 90 degrees abduction, P = .001) when both groups were compared, showing a better outcome in the EPOCA group for all parameters. Radiologic findings, like heterotopic ossification, glenoid erosion, or subluxation, had no significant influence on the outcome in this study. Accurate placement of the tuberosities and healing at the bone-bone interface of the rotator cuff seem to be the most important factors influencing the outcome in prosthetic care of fractures.", "In a randomized prospective comparative study, we treated 28 patients with a fresh fracture of the proximal humerus alternating with a classical Desault-bandage or with the new Gilchrist-bandage. The two different bandages had no influence on the fracture healing or the functional end results. The Gilchrist-bandage was clearly superior to the Desault-bandage in a subjective and objective appreciation: the patients had less complaints in applying the bandage, had less skin irritations and felt less pain during the whole immobilisation period.", "locking intramedullary nails and locking plates specially designed for proximal humeral fractures are widely used. The purpose of our study was to compare the outcomes between these two types of implants in patients with a two-part surgical neck fracture. The advantages and shortcomings of each method were analyzed.\n a prospective randomized study was performed. Fifty-one consecutive patients with a fresh two-part surgical neck fracture were randomized to be treated with a locking intramedullary nail (n = 25) or a locking plate (n = 26). Clinical and radiographic assessments were conducted at one year and three years after the surgery. A visual analog scale (VAS) was used to assess shoulder pain. The American Shoulder and Elbow Surgeons (ASES) scores and Constant-Murley scores were recorded to evaluate shoulder function.\n fracture union was achieved in all patients within three months after the surgery. At one year postoperatively, a significant difference (p = 0.024) was found with regard to the complication rate between the locking plate group (31%) and the locking nail group (4%). The average ASES score, median VAS score, and average strength of the supraspinatus were significantly better in the locking plate group (90.8 compared with 83.6 points [p = 0.021], 1.0 compared with 0.5 point [p = 0.042], and 77.4% compared with 64.3% [p = 0.032]). At three years postoperatively, no significant difference could be found in terms of any parameter between the two groups. Significant improvement in the VAS pain scores, ASES scores, and Constant-Murley scores were found between the one-year and three-year follow-up examinations in each group.\n satisfactory results can be achieved with either implant in the treatment of two-part proximal humeral surgical neck fractures. There was no difference regarding the ASES scores between these two implants at the time of the final, three-year follow-up. The complication rate was lower in the locking intramedullary nail group, while fixation with a locking plate had the advantage of a better one-year outcome.\n therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.", "Monoaxial and polyaxial screw insertion are used in angular stable plating of displaced proximal humeral fractures. Aim of the study was to compare both fixation techniques by radiographic evaluation.\n Prospective randomized treatment with monoaxial or polyaxial screw insertion in angular stable anatomic preshaped plates of displaced proximal humeral fractures. Analysis of standardized true anterior-posterior (true a.p.) and outlet-view radiographs at 1 day, 6 weeks, 3 months, and 6 months after surgery by two radiologists with respect to radiographic evidence of secondary varus displacement, cut out of screws, osteonecrosis, and hardware failure. Secondary varus displacement was defined as a varus decrease of the humeral head-shaft angle of > 10 degree in true a.p. radiographs.\n Sixty-six consecutive patients (48 women, [72.7%]; 18 men, [27.3%]; mean age 67.7 years [95% CI, 63.9-71.6]) with displaced proximal humeral fractures were evaluated in this study. Nineteen patients (29%) showed secondary varus displacement of > 10-degree angle. In 6 cases (9%), intra-articular cut out of screws was found. Furthermore, 1 case (2%) of nonunion was observed. No relationship between monoaxial and polyaxial screw insertion was found regarding occurrence of secondary varus displacement (monoaxial, 11/polyaxial, 8; p = 0.91) or screw cut out (monoaxial, 4/polyaxial, 2; p = 0.64). Prevalence of secondary varus displacement and hardware cut out was related to patients age (p = 0.02) and fracture pattern, according to Neer- and AO/OTA-classification (p < 0.001). The average immediate postoperative head-shaft angle was 135.2 degrees (CI, 132.3-138.1) in the group without radiographic complication, compared with 126.7-degree angle (CI, 123.6-129.7) among those with secondary varus displacement of > 10-degree angle and screw cut out (p < 0.001). Furthermore, in cases of an immediate postoperative head-shaft angle of < 130 degrees, there was a 48% incidence of secondary varus dislocation (n = 13) versus 15% in cases with a head-shaft angle > 130 degrees (n = 6, p = 0.004).\n Monoaxial and polyaxial screw insertion allow for mechanical stabilization in angular stable plating of unstable proximal humerus fractures. Radiographic evidence of secondary varus displacement of > 10-degree angle and screw cut out was seen similarly often in both fixation techniques. To avoid secondary varus displacement and screw cut out, restoration of a humeral head-shaft angle of > 130 degrees seems to be important in monoaxial and polyaxial fixation of proximal humeral fractures.", "A poor outcome arising from a minimally displaced fracture of the neck of the humerus may be the result of a contracture of the capsule of the glenohumoral joint. Pulsed high frequency electromagnetic energy (PHFE) is an electrotherapy to reduce pain and swelling and to enhance healing. If PHFE is effective, early mobilization of the injured shoulder will be possible, reducing the risk of joint capsule contracture. We therefore conducted a double-blind trial of PHFE in minimally displaced fractures of the neck of the humerus. Early physiotherapy produced an excellent outcome in all cases. The functional outcome depended on age rather than time of starting treatment, although a relationship was found between the time of starting treatment and the duration of therapy required. The use of PHFE did not improve the result further.", "In a prospective randomised study, comprising 30 aged patients with fractures of the proximal humerus (4-fragment fractures according to Neer) minimal osteosynthesis was compared to primary endoprosthetic replacement. The Constant score was used for evaluation during follow-up. After one year the results were similar in both groups. There were two complications necessitating revision surgery among the patients with minimal osteosynthesis and in four cases the implants had to be removed. In the group with primary endoprosthetic repair neither complications nor revision surgery occurred. Primary endoprosthetic replacement for the treatment of proximal humeral fractures appears as a therapeutic option with a low complication rate and a satisfying functional outcome. In older patients we need a safe mode of therapy permitting early mobilization and quick discharge from the hospital back to the patient's home. Endoprosthetic replacement fulfils these demands since it resembles a \"one time surgery\" without the risk of revision surgery for implant loosening, pseudarthrosis or ischemic necrosis of the humeral head.", "Four-part fractures of the upper end of the humerus are uncommon injuries and there is still dispute about the best form of management. A retrospective study of 32 patients with these injuries has shown that non-operative management is frequently followed by persistent pain, stiffness and dysfunction of the shoulder. A prospective study of 49 patients with this injury presenting at the Bristol Royal Infirmary has shown that reconstruction of the upper end of the humerus with insertion of a Neer prosthesis will usually restore comfort and function. Whichever regimen is employed, disability is prolonged and dedicated physiotherapy is essential in their management.", "We randomised 40 elderly patients of mean age 74 years with displaced three- or four-part fractures of the humerus to either conservative treatment or tension-band osteosynthesis. At one year and after three to five years, clinical follow-up showed no functional differences between the two groups of patients, with optimal function achieved within one year. There were major complications only in the surgically-treated group. Radiological review showed that surgery had improved the position of the fractured humeral head, but this was not reflected in improved function. Semi-rigid fixation with tension-band wiring of displaced multifragment fractures of the proximal humerus in the elderly did not improve the functional outcome when compared with conservative treatment.", "The aim of the study was to compare the medical aspects of alternative surgical methods for treatment of proximal humerus fractures in specific indications (two- and three- fragment fractures).\n A prospective randomised study on surgical treatment of two- and three-fragment fractures of the proximal humerus was carried out at the Department of Surgery, University Hospital in Hradec Králové, from January 2006 till January 2010. The study comprised patients with proximal humerus fractures indicated for surgical treatment. Study inclusion criteria were as follows: informed consent, AO fracture types A2, A3, B1 or C1, age between 18 and 80 years, and patient compliance. Exclusion criteria included open fracture, associated injury (AIS . 2), open growth plates, or such state of the patient's health that would limit the extent of surgery. Two groups were compared. One included patients treated by the Zifko method of minimally invasive osteosynthesis with intramedullary K-wire insertion (MIO group) and the other (ORIF group) consisted of patients undergoing open reduction with angle-stable osteosynthesis using a Philos plate (Synthes, Switzerland). The patients were randomised to the groups by a computer programme which facilitates the maintenance of homogeneity of the groups compared. The procedure in each patient was based on the sealed-envelope method.\n The ORIF group comprised 28 patients. It took them an average of 27.2 weeks (9-72) to regain normal upper limb function. The final CM score was 86.6% (64-100%) as compared with the healthy limb. Excellent and good results were achieved in 89% of the patients; complications were recorded in 39% of them. The MIO group included 27 patients. The fractures healed in all of them. Normal upper limb function was regained at an average of 21.4 weeks (13-36). The final CM score was 87.5% (52-100%) in comparison with the healthy limb. Excellent and good results were achieved in 89% and complications developed in 33% of the patients.\n The statistical evaluation of the results, using the unpaired t-test, did not show any significant differences either in functional outcomes or the number of complications between the two groups. The only significant difference was found in operative times (117 min and 72 min in ORIF and MIO groups, respectively). The difference in time needed to regain limb function (27 and 21 weeks) was at a marginal level of statistical significance. With both methods 89% of excellent and good results were achieved, and a similar number of patients had complications (11 and 9).", "This study aims to evaluate the costs and health outcome for surgical and conservative treatment of displaced proximal humeral fractures.\n This study is a randomised controlled trial.\n This study included 50 patients aged 60 or older admitted to hospital with a severely displaced three- or four-part fracture.\n The patients were treated surgically with an angular stable interlocking implant (25 patients) or conservative treatment (25 patients).\n The outcomes measured included quality-adjusted life years (QALYs) and societal costs.\n At 12 months' follow-up, the mean difference in the number of QALYs was 0.027 (95% confidence interval (CI)=-0.025, 0.078) while the mean difference in total health-care costs was 597 euro in favour of surgery (95% CI=-5291, 3777).\n There was no significant difference in QALYs or costs between surgical and conservative treatment of severe displaced proximal humeral fractures.\n Copyright 2009 Elsevier Ltd. All rights reserved.", "Two methods of physiotherapy after fracture of the proximal end of the humerus were compared. The study was designed as a randomized, controlled and single-blind trial. Twenty patients were assigned to two groups 10-12 days after the injury. One group was treated conventionally, the other received instructions in self-training with follow-up control of results. Objective examination and subjective assessment were made at five intervals, up to one year after the injury. The greatest improvement in function was shown in both groups between 3 and 8 weeks. The patients deemed their daily life functions to be normal 8 weeks after the injury. The objective assessment was normal at later stages. No significant differences were found between the two groups in any of the tests. Instruction in self-training with control of results including objective assessments are therefore an adequate method in the rehabilitation of these patients.", "We undertook a prospective, controlled trial which compared two rehabilitation programmes for 86 patients who sustained two-part fractures of the proximal humerus. Patients were randomised either to receive immediate physiotherapy within one week (group A) or delayed physiotherapy after three weeks of immobilisation in a collar and cuff sling (group B). At 16 weeks after the fracture, patients in group A had less pain (p < 0.01) and had greater shoulder function (p < 0.001) than those in group B. At 52 weeks, the differences between the groups had reduced. Although group A still had greater shoulder function and less pain, there was no statistical difference when compared with group B. By analysis of the area under the curve, an overall measure up to the 52-week period, group A experienced less pain as measured by the SF36 general health questionnaire and had improved shoulder function. Our results show that patients with two-part fractures of the proximal humerus who begin immediate physiotherapy, experience less pain. The gains in shoulder function persist at 52 weeks which suggests that patients do not benefit from immobilisation before beginning physiotherapy.", "The aim of the study was to report the 2-year outcome after a displaced 3-part fracture of the proximal humerus in elderly patients randomized to treatment with a locking plate or nonoperative treatment.\n We included 60 patients, mean age 74 years (range, 56-92), 81% being women. The main outcome measures were the Constant and Disabilities of the Arm, Shoulder and Hand (DASH) scores and the health-related quality of life (HRQoL) according to the EQ-5D.\n At the final 2-year follow-up, the results for range of motion (ROM), function and HRQoL were all in favor of the locking plate group. The mean flexion in the locking plate group was 120° compared to 111° in the nonoperative group (P = .36) and the mean abduction was 114° compared to 106° (P = .28). The corresponding values for the Constant score were 61 versus 58 (P = .64), for DASH 26 versus 35 (P = .19), and the mean EQ-5D (index) score was 0.70 compared to 0.59 (P = .26). In spite of good primary reduction in 86% of the fractures in the locking plate group, 13% of the patients had a fracture complication requiring a major reoperation and 17% had a minor reoperation.\n The results of our study indicate an advantage in functional outcome and HRQoL in favor of the locking plate compared to nonoperative treatment in elderly patients with a displaced 3-part fracture of the proximal humerus, but at the cost of additional surgery in 30% of the patients.\n Copyright © 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.", "The aim of the study was to report the 2-year outcome after a displaced 4-part fracture of the proximal humerus in elderly patients randomized to treatment with a hemiarthroplasty (HA) or nonoperative treatment.\n We included 55 patients, mean age 77 (range, 58-92) years, 86% being women. Follow-up examinations were done at 4, 12, and 24 months. The main outcome measures were health-related quality of life (HRQoL) according to the EQ-5D and the DASH and Constant scores.\n At the final 2-year follow-up the HRQoL was significantly better in the HA group compared to the nonoperative group, EQ-5D (index) score 0.81 compared to 0.65 (P = .02). The results for DASH and pain assessment were both in favor of the HA group, DASH score 30 versus 37 (P = .25) and pain according to VAS 15 versus 25 (P = .17). There were no significant differences regarding the Constant score or range of motion (ROM). Both groups achieved a mean flexion of approximately 90-95° and a mean abduction of 85-90°. The need for additional surgery was low: 3 patients in the HA group and 1 patient in the nonoperative group.\n The results of the study demonstrated a significant advantage in quality of life in favor of HA, as compared to nonoperative treatment in elderly patients with a displaced 4-part fracture of the proximal humerus. The main advantage of HA appeared to be less pain while there were no differences in ROM.\n Copyright © 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.", "The purpose of this study was to evaluate the clinical benefit of medial support screws for locking plating of proximal humerus fractures.\n Seventy-two consecutive patients underwent prospective treatment for proximal humerus fractures with locking plates between October 2007 and September 2008. Sixty-eight patients accomplished a mean 30.8-month follow-up and were randomized into two groups: 39 patients were treated with only a locking plate and were classified in the -MSS (medial support screw) group, and 29 patients were included in the + MSS group, which were fixed with additional medial support screws. Clinical and radiological investigations were performed in both groups.\n The fractures united at an average of 13.6 weeks after final surgery. Comparably better shoulder function recovery was achieved in the +MSS group with regard to the Constant shoulder score (P = 0.01), with the respective excellent and good rates of 79% and 62%. Eleven patients developed various complications. A statistical difference (P = 0.036) was observed regarding the failure rate (23.1% in the -MSS group vs. 3.4% in the +MSS group). The early loss of fixation was related to higher age (P < 0.001) and less initial neck-shaft angle (NSA) (P = 0.011) of the patients. However, bone mineral density was not significantly associated with loss of fixation (P = 0.076). Although no difference was found in all types of the fractures between the +MSS and -MSS groups regarding immediate postoperative NSA, we observed a significantly lower final NSA in the -MSS group and greater secondary angle loss in the subgroup of Neer three-part (P = 0.033 and 0.015, respectively) and four-part fractures (P = 0.043 and 0.027).\n Anatomical reduction can substantially decrease the risk of postoperative failure in locking plating of proximal humerus fractures. Medial support for proximal humerus fractures seems to have no benefits in Neer two-part fractures. However, the additional medial support screws inserted into the medio-inferior region of the humeral head may help to enhance mechanical stability in complex fractures and allow for better maintenance of reduction." ]

[ "10865480", "14660913", "12728089", "10190921" ]

[ "The effectiveness of topical treatment in discharging ears with in-dwelling ventilation tubes.", "Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes.", "Antibiotic treatment of acute otorrhea through tympanostomy tube: randomized double-blind placebo-controlled study with daily follow-up.", "Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes." ]

[ "The efficacy and tolerability of topical treatment (both drops and spray) in the treatment of otorrhoea in those ears with ventilation tubes in-situ was studied. Sixty patients were randomised into two treatment groups. One group used an antibacterial/anti-inflammatory ear drop preparation (Otosporin) and the other group a similar preparation administered as an ear spray (Otomize). A 'blind' clinical assessment was made one and three weeks after commencing treatment. Both treatments (drops and spray) significantly improved patients' symptoms and signs after one week (p < 0.001). The spray was significantly easier to administer (p < 0.01) and caused less discomfort on application (p < 0.02).", "To determine whether topical administration of a corticosteroid improves resolution of acute tympanostomy tube otorrhea when combined with topical antibiotic drops.\n Randomized, patient-masked, parallel-group, multicenter trial of topical otic ciprofloxacin/dexamethasone versus topical ciprofloxacin alone in 201 children aged 6 months to 12 years with acute otitis media with tympanostomy tubes (AOMT) of less than or equal to 3 weeks' duration and visible otorrhea.\n Eligible patients were randomized to receive three drops of either ciprofloxacin 0.3%/dexamethasone 0.1% or ciprofloxacin 0.3% into the affected ear or ears twice daily for 7 days. Clinical signs and symptoms of AOMT were evaluated on days 1 (baseline), 3, 8 (end-of-therapy), and 14 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries.\n The mean time to cessation of otorrhea in the microbiologically culture-positive patient population (n = 167) was significantly shorter with topical ciprofloxacin/dexamethasone than with ciprofloxacin alone (4.22 vs. 5.31 days; P =.004). This resulted in significantly better clinical responses on days 3 and 8 (P <.0001 and P =.0499, respectively). However, there were no significant differences between the two treatment groups in either the clinical response or the microbial eradication rate by day 14.\n Topical otic treatment with ciprofloxacin/dexamethasone is superior to treatment with ciprofloxacin alone and results in a faster clinical resolution in children with AOMT. The contribution of the corticosteroid in achieving a 20% reduction (1.1 day) in time to cessation of otorrhea is clinically meaningful and represents an important advance over single-agent antibiotic therapy.", "The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea.\n Randomized, double-blind, placebo-controlled study in outpatient setting.\n Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study.\n Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube.\n Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid.\n The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days).\n Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid.", "To determine the efficacy of a short course of oral prednisolone as an adjuvant therapy for acute otitis media draining through tympanostomy tubes.\n In a randomized, double-blind, placebo-controlled study, children with acute discharge (<48 hours) through tympanostomy tubes received either prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were examined daily at the study clinic until the drainage ceased.\n The median duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range, 1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in the children receiving placebo (P <.001). The duration of otorrhea was </=2 days in 21 (91%) children in the prednisolone group, compared with 8 (30%) children in the placebo group (P <.001).\n Oral prednisolone appears to be modestly effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes in children. Further studies seem warranted to determine whether short-term use of steroids early during the course of acute otitis media would also reduce the duration of middle ear effusion in children with intact tympanic membranes." ]

[ "3801827", "17414601", "16959690", "15541982", "7633976", "16136287", "16914772", "15531229", "12056469", "17356139", "14560228", "1768031", "9725389", "11679600", "14649578", "10477639", "1462639", "8384050", "10565650", "6156554", "6613136", "8682467", "7928148", "12735583", "17085137" ]

[ "Reduction of post-operative bleeding after transurethral resection of the prostate by local instillation of fibrin adhesive (Beriplast).", "Application of fibrin glue sealant after hepatectomy does not seem justified: results of a randomized study in 300 patients.", "A pilot study of the effects of Vivostat patient-derived fibrin sealant in reducing blood loss in primary hip arthroplasty.", "The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study.", "Fibrin sealant reduces suture line bleeding during carotid endarterectomy: a randomised trial.", "Randomized trial comparing Quixil surgical sealant with Kaltostat hemostatic dressing to control suture line bleeding after carotid endarterectomy with ePTFE patch reconstruction.", "Effectiveness of autologous fibrin tissue adhesive in reducing postoperative blood loss during total hip arthroplasty: a prospective randomised study of 100 cases.", "Does fibrin glue sealant decrease the rate of pancreatic fistula after pancreaticoduodenectomy? Results of a prospective randomized trial.", "Tissucol application in dermolipectomy and incisional hernia repair.", "Comparison of topical fibrin spray and tranexamic acid on blood loss after total knee replacement: a prospective, randomised controlled trial.", "Prospective randomized multicenter trial of fibrin sealant versus thrombin-soaked gelatin sponge for suture- or needle-hole bleeding from polytetrafluoroethylene femoral artery grafts.", "[Use of a biological glue in partial pulmonary excision surgery. Results of a controlled trial in 50 patients].", "Vivostat system autologous fibrin sealant: preliminary study in elective coronary bypass grafting.", "Use of fibrin sealant to reduce bloody drainage and hemoglobin loss after total knee arthroplasty: a brief note on a randomized prospective trial.", "Fibrin sealant reduces perioperative blood loss in total hip replacement.", "Hemostatic efficacy of fibrin sealant (human) on expanded poly-tetrafluoroethylene carotid patch angioplasty: a randomized clinical trial.", "Comparison of topical hemostatic agents in elective hepatic resection: a clinical prospective randomized trial.", "The use of fibrin adhesive for hemostasis after liver resection.", "The use of fibrin tissue adhesive to reduce blood loss and the need for blood transfusion after total knee arthroplasty. A prospective, randomized, multicenter study.", "[New method of hemostasis with adhesives in adenomectomy].", "[Modification of suprapubic prostatectomy using a biological gluing technic].", "Fibrin glue effectiveness and tolerance after elective liver resection: a randomized trial.", "Prevention of pleural effusion after hepatectomy using fibrin sealant.", "Fibrin glue in pulmonary resection: a prospective, randomized, blinded study.", "A prospective, randomized trial evaluating the safety and efficacy of fibrin sealant in tubeless percutaneous nephrolithotomy." ]

[ "A method for instilling a two-component fibrin adhesive into the prostatic cavity after transurethral resection of the prostate is described. In a prospective, controlled study, 30 consecutive patients undergoing transurethral prostatectomy (TURP) were randomised either to receive treatment with the local instillation of fibrin adhesive into the prostatic cavity or to a control group that received no special treatment post-operatively. There were no complications either during application of the fibrin adhesive or in the follow-up period. Post-operative blood loss was significantly reduced in the fibrin group (P less than 0.01).", "To evaluate the efficacy, amount of hemorrhage, biliary leakage, complications, and postoperative evolution after fibrin glue sealant application in patients undergoing liver resection.\n Fibrin sealants have become popular as a means of improving perioperative hemostasis and reducing biliary leakage after liver surgery. However, trials regarding its use in liver surgery remain limited and of poor methodologic quality.\n A total of 300 patients undergoing hepatic resection were randomly assigned to fibrin glue application or control groups. Characteristics and debit of drainage and postoperative complications were evaluated. The amount of blood loss, measurements of hematologic parameters liver test, and postoperative evolution (particularly involving biliary fistula and morbidity) was also recorded.\n Postoperatively, no differences were observed in the amount of transfusion (0.15 +/- 0.66 vs. 0.17 +/- 0.63 PRCU; P = 0.7234) or in the patients that required transfusion (18% vs. 12%; P = 0.2), respectively, for the fibrin glue or control group. There were no differences in overall drainage volumes (1180 +/- 2528 vs. 960 +/- 1253 mL) or in days of postoperative drainage (7.9 +/- 5 vs. 7.1 +/- 4.7). Incidence of biliary fistula was similar in the fibrin glue and control groups, (10% vs. 11%). There were no differences regarding postoperative morbidity between groups (23% vs. 23%; P = 1).\n Application of fibrin sealant in the raw surface of the liver does not seem justified. Blood loss, transfusion, incidence of biliary fistula, and outcome are comparable to patients without fibrin glue. Therefore, discontinuation of routine use of fibrin sealant would result in significant cost saving.", "A pilot study evaluated the effectiveness of Vivostat patient-derived fibrin sealant in reducing blood loss in patients who underwent primary hip arthroplasty. Eighty adult patients undergoing elective surgery were randomized to receive either Vivostat sealant or control (no additional hemostatic treatment). Patients allocated Vivostat sealant donated 120 mL of blood, which was then processed perioperatively to produce a fibrin sealant that was applied to the bleeding wound surfaces just before closure. Transfusion requirements, blood loss during surgery, drain volumes, and daily hematocrit and hemoglobin levels were measured. Hospitalization times, adverse events, and postoperative wound complications were also monitored. Blood loss during surgery and wound drainage volume was lower in the Vivostat group than in the control group, although the differences were not significantly different. Transfusion requirements (median, 270 mL of packed red blood cells) and hospitalization times (both median 7 days) were the same for both groups. No adverse events related to the use of Vivostat occurred. There were indications of a possible reduction in the incidence of postoperative wound oozing (15% vs 25%) and hematomas (6% vs 11%) with the use of Vivostat compared with the control group, although differences were not statistically significant. In conclusion, in this pilot study, use of Vivostat patient-derived fibrin in hip arthroplasty was not associated with a significant reduction in blood loss. Further studies, with larger numbers of patients, may be warranted to investigate a possible benefit of Vivostat in reducing postoperative wound complications.", "Postoperative air leakage is the most frequent complication after pulmonary surgery. The development of modern surgical techniques has been influenced strongly by the need to manage air leakage effectively during pulmonary resection. This study evaluated the effect of using an autologous fibrin sealant (Vivostat) during lobectomy on morbidity following surgery.\n This was a prospective, blinded, randomised clinical study. Patients undergoing lobectomy were enrolled into two groups (Vivostat or non-treatment control, 20 per group). Air leakage was measured over a 1-h period (using a mechanical suction pump) on the day of operation, and both air leakage and bleeding/exudation (drainage volume) were recorded every morning postoperatively until the chest tubes were removed. Personnel recording these parameters were blinded to the intervention received. Results: Compared with the control group, mean bleeding/exudate volumes were significantly reduced in the Vivostat group (day 1,370 vs. 525 ml; total, 424 vs. 782 ml; both P<0.001), and drains were inserted for a shorter time (medians, 1 vs. 2 days, P=0.07). Significantly fewer patients had air leakage at any time in the Vivostat group (40 vs. 80%, P=0.02), and air leakage volumes were significantly lower compared with the control group (median differences: day of surgery: 0.6l/min, P=0.01; total 0.8l/min, P=0.03). Postoperative hospitalisation time was shorter in the Vivostat group than in the control group but the difference was not significant (0.5 days, P=0.12).\n Vivostat fibrin sealant significantly reduces post-surgical air leakage and drainage volumes following lobectomy in pulmonary surgery and is suitable for routine use in this procedure.", "To determine whether topical fibrin sealant reduced suture line bleeding during carotid endarterectomy with polytetrafluoroethylene (PTFE) patch closure.\n Prospective randomised non-blinded control trial.\n Regional vascular surgery unit.\n Seventeen patients undergoing carotid endarterectomy were randomised either to receive fibrin sealant as a topical haemostatic agent at the arteriotomy suture line or to act as control.\n Time taken to achieve haemostasis at the suture line. Intraoperative blood loss. Total operative time.\n The median time to achieve haemostasis was 5.5 min (range 4-31 min) in the treatment group and 19 min (range 10-47 min) in the control group. This difference was statistically significant p < 0.005 by Mann-Whitney test. There was no statistical difference in total operative time. Operative blood loss was lower in the treatment group (median 420ml, range 300-500ml) than in the control group (median 550ml, range 350-1200ml) but this difference was not statistically significant. One patient in the control group suffered a perioperative thrombo-embolic event.\n Fibrin sealant is an effective topical haemostatic agent for arteriotomy suture lines involving PTFE material.", "Following carotid endarterectomy (CEA), patch angioplasty provides a significant reduction in the risk of perioperative complications. The expanded polytetrafluoroethylene (ePTFE) patch is strong, is resistant to infection, and has low thrombogenicity; but it remains unpopular because of its tendency of prolonged bleeding at the suture line. We aimed to investigate whether the application of Quixil sealant to the suture line could improve the time to achieve hemostasis and reduce local blood loss when compared to a standard topical hemostat Kaltostat. A prospective, randomized trial of 20 patients undergoing CEA was undertaken. Patients were randomized to receive either Quixil sealant (treatment group) or topical Kaltostat (controls) as a hemostatic agent to the patch suture line. Hemostasis was defined as no bleeding at the suture line for 1 minute. Statistical analysis was performed using the Mann-Whitney test. The two groups had a similar age and sex distribution. The mean age was 71 years, and there were seven men and three women in each group. The time to achieve hemostasis was significantly lower in the Quixil group (median 2.5 minutes, range 1-4 minutes) compared to the controls (median 17 minutes, range 7-59 minutes) (p < 0.001). Blood loss after clamp release was also significantly reduced in the Quixil group; median 24.5 ml (range 5.5-105.0 ml) versus 203 ml (range 54.5-817.0 ml) (p < 0.001). This study has demonstrated that Quixil human surgical sealant is an effective sealant of ePTFE patch suture holes and does not compromise the patch repair. It could be used during other vascular procedures involving ePTFE.", "To evaluate the effectiveness of autologous fibrin tissue adhesive (auto-FTA) in reducing blood loss during cementless total hip arthroplasty (THA).\n From September 2000 to August 2001, 100 patients who predonated 400 ml of autologous blood were randomised to undergo either standard treatment with auto-FTA (auto-FTA group) or standard treatment alone (control group). The volume of postoperative blood loss and the decrease in haemoglobin level were measured. All patients were followed up for 3 years to evaluate the rate of bone ingrowth and heterotopic ossification.\n The mean postoperative blood loss was 580 ml (standard deviation [SD], 240 ml) in the auto-FTA group and 810 ml (SD, 341 ml) in the control group; the difference was significant (230 ml, p<0.001). The decrease in haemoglobin concentration was 17 g/l (SD, 11 g/l) in the auto-FTA group and 22 g/l (SD, 12 g/l) in the control group. The difference was significant (5 g/l, p=0.03). The percentage of total blood loss of >1200 ml in any single patient was significantly lower in the auto-FTA group (4%) than in the control group (20%) [p=0.01].\n Auto-FTA is a safe and effective means of reducing perioperative blood loss in THA.", "Despite substantial improvements in perioperative mortality, complications, and specifically the development of a pancreatic fistula, remain a common occurrence after pancreaticoduodenectomy. It was the objective of this study to evaluate the role of fibrin glue sealant as an adjunct to decrease the rate of pancreatic fistula after pancreaticoduodenectomy. One hundred twenty-five patients were randomized after pancreaticoduodenal resection only if, in the opinion of the surgeon, the pancreaticojejunal anastomosis was at high risk for development of a pancreatic anastomotic leak. After completion of the pancreaticojejunal anastomosis, the patients were randomized to topical application of fibrin glue sealant to the surface of the anastomosis or no such application. The primary postoperative end points in this study were pancreatic fistula, total complications, death, and length of hospital stay. A total of 59 patients were randomized to the fibrin glue arm, whereas 66 patients were randomized to the control arm and did not receive fibrin glue application. The pancreatic fistula rate in the fibrin glue arm of the study was 26% vs. 30% in the control group (p = not significant [NS]). The mean length of postoperative stay for all patients randomized was similar (fibrin glue = 12.2 days, control = 13.6 days) and the mean length of stay for patients in whom pancreatic fistula developed was also not different (fibrin glue = 18.9 days, control = 21.7 days). There were no differences with respect to total complications or specific complications such as postoperative bleeding, infection, or delayed gastric emptying. These data demonstrate that the topical application of fibrin glue sealant to the surface of the pancreatic anastomosis in this patient population undergoing high-risk pancreaticojejunal anastomosis did not reduce the incidence of pancreatic fistula or total complications after pancreaticodudodenectomy. There seems to be no benefit regarding the use of this substance in this setting.", "Biological adhesives have a lot of applications in surgical procedures. Here we present a prospective study with the aim of analyzing results of the application of Tissucol between the muscle layers and subcutaneous tissue after incisional hernia repair with polypropylene mesh and associated dermolipectomy. We assess clinical and technical parameters, local morbidity, and hospital stay. Fifty-six patients were divided into two groups. Patients with whom we used fibrin glue were older, with more obesity (P < 0.005) with associated diseases, and their incisional hernias were larger and more complicated to repair. Patients in the Tissucol group developed less local morbidity (hematomas or abscesses; P < 0.01), had a shorter mean hospital stay (P < 0.01), and required less wound care. The use of Tissucol improves the results of surgical repair of large abdominal incisional hernias repaired by mesh placement and dermolipectomy, and it decreases global morbidity and hospital stay are reduced.", "We performed a randomised, controlled trial involving 150 patients with a pre-operative level of haemoglobin of 13.0 g/dl or less, to compare the effect of either topical fibrin spray or intravenous tranexamic acid on blood loss after total knee replacement. A total of 50 patients in the topical fibrin spray group had 10 ml of the reconstituted product applied intra-operatively to the operation site. The 50 patients in the tranexamic acid group received 500 mg of tranexamic acid intravenously five minutes before deflation of the tourniquet and a repeat dose three hours later, and a control group of 50 patients received no pharmacological intervention. There was a significant reduction in the total calculated blood loss for those in the topical fibrin spray group (p = 0.016) and tranexamic acid group (p = 0.041) compared with the control group, with mean losses of 1190 ml (708 to 2067), 1225 ml (580 to 2027), and 1415 ml (801 to 2319), respectively. The reduction in blood loss in the topical fibrin spray group was not significantly different from that achieved in the tranexamic acid group (p = 0.72).", "We evaluated the safety and efficacy of the fibrin sealant Beriplast P (FSBP; Aventis-Behring) for hemostasis in anastomosis of polytetrafluoroethylene (PTFE) grafts to the femoral artery.\n In a single-blinded randomized prospective multicenter clinical trial, FSBP was compared with thrombin-soaked gelatin sponge (TSG) for efficacy in stopping bleeding from needle or suture holes in PTFE grafts after anastomosis to the femoral artery. Patients were randomized to FSBP application, which requires a 3-minute period of arterial clamping to enable the fibrin clot to adhere, or to TSG application, which requires pressure from gauze sponges, after completion of the femoral artery anastomosis. The primary end point was hemostasis, defined as absence of any detectable bleeding as judged by the operating surgeon, by 4 minutes after randomization. Secondary end points included actual time from randomization to hemostasis, time to beginning of wound closure, measured blood loss (weighed sponges), incidence of recurrent bleeding, stay in the intensive care unit, and hospital length of stay. Data were analyzed with the intention-to-treat method.\n Two hundred thirty-five subjects were enrolled at 26 medical centers; 34 were subsequently excluded from the study. Of the 201 randomized subjects, 100 received FSBP and 99 received TSG. Hemostasis was achieved by 4 minutes in 64 subjects (63%) in the FSBP group and 40 subjects (40%) in the TSG group (P =.0018). In the FSBP group, compared with the TSG group, time to hemostasis was shorter (median, 4.0 minutes; 95% confidence interval [CI], 3.8-4.18 minutes vs median, 5.6 minutes, 95% CI, 4.5-7.0; P =.008), blood loss was less (mean, 4.0 +/- 29.7 g vs mean, 15.6 +/- 28.4 g; P <.0001), and time to wound closure was shorter (median, 15 minutes; 95% CI, 10.47-18.67 minutes vs median, 22.8 minutes; 95% CI, 18.67-30.67; P =.005). There were no differences in recurrent bleeding or any other adverse events. There was no significant difference in ICU stay, but hospital length of stay was shorter in the FSBP group compared with the TSG group, and the difference approached significance (median, 6.5 days; 95% CI, 5.00-7.00 days vs median, 7.0 days; 95% CI,. 6.00-8.00 days; P =.0565).\n FSBP is more effective than TSG for achieving hemostasis of needle or suture hole bleeding from PTFE femoral artery grafts.", "A controlled study concerning the surgical use of a fibrin glue was conducted in 50 patients undergoing partial pulmonary excision. In 25 of these patients, chosen at random, hemostasis and aerostasis of the fissural, and/or intersegmentary dissection planes were achieved by electrocoagulation, in the other 25 by the application of fibrin glue. The statistical study did not show any significant difference between the two groups in terms of the surgical indication, the type of excision and the associated surgical procedures (pleurectomy and parietectomy). No significant statistical difference was observed concerning the quality of aerostasis, the post-operative drainage, the persistance of residual collection or faulty reexpansion after removal of the latter, and the necessity for repeated drainage. The same applied to the length of post-operative hospital stay. This study seems to demonstrate that the surgical application of fibrin glue on the fissural and/or intersegmentary dissection planes is feasible but, as compared to electrocoagulation, does not significantly improve the quality of the surgical results for partial pulmonary excision; however its use could reduce the duration of post-operative drainage.", "The Vivostat System is a medical device for the preparation of an autologous fibrin sealant from 120 mL of the patient's blood in the operating room. The system is fully automated and microprocessor controlled and is made up of three components: an automated processor unit, an automated applicator unit, and a disposable, single-patient-use unit, which includes a preparation set and a Spraypen applicator. The biochemical process is initiated by batroxobin, which acts upon the fibrinogen in the patient's plasma. The completion of the process depends entirely on endogenous thrombin in producing the sealant.\n Twenty-four volunteer patients undergoing elective primary coronary artery bypass grafting were randomized to either conventional hemostasis (control group) or the use of Vivostat fibrin sealant as an adjunct to conventional hemostasis. The patients were followed up at 1 month and 1 year.\n The preparation process was completed in 30 minutes. No safety issues associated with the use of the sealant were identified. From 120 mL of the patient's blood the yield of fibrin sealant was 4.5 mL (range, 3.9 to 4.8 mL). There was a favorable trend toward lower amounts of chest tube drainage in the Vivostat group. In the Vivostat group, 1 of 11 patients (9%) required a perioperative transfusion and in the control group 3 of 12 patients (25%) required a perioperative transfusion.\n It is possible to prepare autologous fibrin sealant with the Vivostat system in 30 minutes. No exogenous thrombin is required. The sealant has no known adverse effects and may prove to be a useful adjunct to hemostasis in cardiothoracic surgery.", "A phase-III trial that included fifty-three patients undergoing unilateral primary total knee arthroplasty with cement was conducted to investigate the hemostatic efficacy of fibrin sealant.\n Following cementing of the joint, 10 mL of fibrin sealant was sprayed onto the wound before tourniquet deflation and wound closure. No placebo was used in the control group. All patients received drains.\n Within twelve hours after the surgery, the amount of bloody drainage was 184.5 +/- 28.9 mL (mean and standard error) in the fibrin-sealant group (information available for twenty-three patients) and 408.3 +/- 54.6 mL in the control group (information available for twenty-three patients) (p = 0.002, after adjustment for variance in the time that the drainage was measured). On the first postoperative day, the hemoglobin level had decreased by 20.1 +/- 2.1 g/L in the fibrin-sealant group (information available for twenty-two patients) and by 27.3 +/- 2.1 g/L in the control group (information available for twenty-four patients). After adjustment for baseline values, the decrease in the hemoglobin level was 28.9% less in the fibrin-sealant group than in the control group (p = 0.005, 95% confidence limits = 10.2, 43.7). There were no seroconversions in the fibrin-sealant group.\n These results suggest that fibrin sealant can safely reduce bloody drainage following total knee arthroplasty while maintaining higher hemoglobin levels.", "Patients (n = 81) undergoing total hip replacement (THR) were randomized to receive either standard of care plus fibrin sealant (FS) (10 mL total) or standard of care alone to evaluate the efficacy of FS for reducing blood loss in THR. Considering the 81 intent-to-treat patients, adjusted perioperative blood loss was reduced significantly in the FS group, by 197 mL [95% CI: 45 mL, 319 mL] or 23.5% [95% CI: 5.4%, 38.1%] (p = 0.014). When protocol violators were eliminated, leaving 73 patients, the adjusted FS group perioperative bleeding was reduced by 221 mL [95% CI: 63 mL, 351 mL] or 27.1% [95% CI: 7.6%, 42.5%] (p = 0.0098).", "The efficacy of solvent-detergent-treated fibrin sealant (human [FSH]) for controlling anastomotic bleeding from expanded polytetrafluoroethylene (ePTFE) patch angioplasty during carotid endarterectomy was evaluated, and FSH was compared with thrombin-soaked gelatin sponge (Gelfoam; TSG).\n The study was of a randomized, open-label, single-site, single-treatment, parallel design that took place in a referral center with hospitalized patients. Forty-seven adult patients (33 men, 14 women) underwent elective carotid endarterectomy. Patients were randomized to receive either FSH (N = 24) or TSG (N = 23). FSH was obtained as an investigational new drug. FSH was applied as a liquid by means of a dual-syringe technique. Heparin anticoagulation, patch thickness, and suture type were standardized. Two different needle sizes were used (CV-6, PT-13: N = 21 [FSH: N = 10, TSG: N = 11]; CV-6, PT-9: N = 26 [FSH: N = 14, TSG: N = 13]). The FSH or TSG was applied to the ePTFE patch, and then blood flow was restored through the carotid artery. Degree of anticoagulation was assessed by anti-factor Xa activity. The time from restoration of carotid blood flow until achieving hemostasis was recorded. The blood loss from patch suture hole bleeding was measured. Completion intraoperative duplex ultrasound scanning was performed in all cases. Heparin was reversed with protamine sulfate. The primary end point was successful hemostasis within 15 minutes of restoration of carotid blood flow. The secondary end points were the amount of blood loss caused by suture line bleeding and the time to achieve hemostasis.\n There was no difference in the number of patients with complete hemostasis at 15 minutes (TSG, 13 of 23; FSH, 12 of 24; P =.77). The measured blood loss was 99.0 +/- 119.9 (SD) mL for TSG, and 105.0 +/- 107.9 mL for FSH (P =.86). The time to hemostasis was the same for both groups (TSG, 16.5 +/- 16.5 minutes; FSH, 16.6 +/- 14.2 minutes; P =.97). Within both treatment groups, the use of larger needles (PT-13) was associated with greater blood loss (FSH, 169.7 +/- 124.2 mL; TSG, 172.7 +/- 151.5 mL) than was the use of smaller needles (PT-9; FSH, 58.8 +/- 66.3 mL; TSG, 34.1 +/- 25.6 mL; P =.036, P =.001, respectively). There were no postoperative strokes or bleeding complications in either group. No abnormalities were shown in either group by means of completion carotid duplex ultrasound scanning.\n FSH was equivalent, but not superior to, TSG in achieving hemostasis during carotid endarterectomy performed with ePTFE patch angioplasty. Adhesion properties of FSH to ePTFE are possibly different than those to native tissue and warrant additional investigation.", "To compare the difference in efficacy of microcrystalline collagen powder (CL) and fibrin glue (FG) in elective hepatic resection, 62 patients (female 14, male 48) with ages ranging from 51 to 75 years were randomly allocated to receive either CL or FG as a topical agent during hepatectomy. There were no significant differences between the patients treated with CL (n = 31) and those treated with FG (n = 31) regarding sex, age, liver function, coagulation function, platelet counts, type of liver resection, and operative duration. A dry cut surface of the liver was obtained during surgery in 27 (87%) patients and 25 (81%) patients treated with CL and FG, respectively. Both CL and FG showed similar hemostatic effects. The CL and FG groups were not different in terms of postoperative rebleeding, bile leakage, or morbidity and mortality rates (6% vs. 6%, 6% vs. 6%, 45% vs. 39%, and 13% vs. 10%, respectively). Of the 52 patients with a dry cut surface of the liver during surgery, 3 patients in the CL group encountered rebleeding (n = 1) or bile leakage (n = 2) from the cut surface postoperatively, while no such complications were noted in the FG group. The results seem to favor FG for reliability in the postoperative period. The application of CL or FG may be better performed with consideration of the characteristics of each agent.", "Bleeding, biliary fistula and subphrenic abscess represent the major postoperative complications after liver surgery. Many different adjuvant methods have been developed for control of hemorrhage from the raw surface of liver, but the superiority of any single method remains to be proved. The use of a two-component fibrin adhesive for the control of solid organ bleeding seems to be promising. This study was to evaluate the efficacy of this fibrin adhesive for control of postoperative bleeding in liver surgery. Forty patients were randomized into two groups, similar in all demographic and clinical conditions. Fibrin adhesive was applied to the raw surface of liver resections at the end of operations for 20 patients. Nothing was applied for the control group. Postoperative bleeding was estimated by multiplying the drain amount by the free hemoglobin concentration, every day. Estimated postoperative bleeding was 8.12 +/- 5.65 gm for patients with fibrin adhesive, 15.57 +/- 14.43 gm for control group. Fibrin adhesive has been used in the treatment of injury to the liver and spleen. In this study, it proved to be useful in the control of postoperative bleeding in liver resection, and hopefully decreasing morbidity.", "Total knee arthroplasty is associated with major postoperative blood loss of approximately 800 to 1200 milliliters, and blood transfusion is frequently required. With the increased concern about the risks of blood transfusion, various methods of blood conservation in orthopaedic surgery have been studied. The most appropriate solution, however, is to reduce the loss of blood during and after an operation. The present prospective, controlled, randomized study was designed to evaluate the hemostatic efficacy of the use of fibrin tissue adhesive in patients managed with total knee arthroplasty.\n Fifty-eight patients who were scheduled to have a total knee arthroplasty were randomly divided into two groups: a control group, in which the standard means of hemostasis were applied, and a treatment group, in which the standard means to control local bleeding were applied and a fibrin tissue adhesive was sprayed on the internal aspects of the operative field before skin closure. All operations were performed in a bloodless field with use of a pneumatic tourniquet. All patients received low-molecular-weight heparin as thromboprophylaxis twelve hours before the operation and every twelve hours postoperatively. Blood loss during the operation was evaluated by measuring the volume in the suction apparatus and by estimating the amount of lost blood in the swabs at the end of the operation. The apparent postoperative lost blood was determined by measuring the volume in the suction-drain bottles. All blood transfusions were recorded.\n The mean apparent postoperative blood loss (and standard deviation) in the fibrin-tissue-adhesive group was 360+/-287.7 milliliters compared with 878+/-403.0 milliliters in the control group, with a mean difference of 518 milliliters (p<0.001). The decrease in the level of hemoglobin was 25+/-10 grams per liter in the treatment group compared with 37+/-12 grams per liter in the control group (p<0.001). Sixteen patients (55 percent) in the control group required a blood transfusion and eight (28 percent) required two units of blood, whereas only five (17 percent) of the patients in the fibrin-tissue-adhesive group required a blood transfusion and only one (3 percent) required two units (p = 0.004). The number of adverse events was comparable between the two groups. None of the adverse events were considered to be related to the use of fibrin tissue adhesive. One death, which was due to massive pulmonary embolism, was reported in the control group. No seroconversion was reported at three and six months after the operation.\n The use of fibrin tissue adhesive in total knee arthroplasty seems to be an effective and safe means with which to reduce blood loss and blood-transfusion requirements. Furthermore, the importance of these findings was enhanced by a significant reduction in blood loss, in the postoperative decrease in the level of hemoglobin, and in blood-transfusion requirements despite preoperative thromboprophylaxis with low-molecular-weight heparin.", "In the transvesical adenomectomy the author used human fibrin adhesive for stopping a bleeding in the prostatic lodge. Thus an essential reduction of the blood loss in the postoperative time was achieved. The difference between the patients who were treated with an adhesive and control patients is significant.", "Fibrinogen cryoprecipitate, thrombin solution and factor XIII concentrate were used for gluing in suprapubic transvesical prostatectomy. The fibrin glue was applied to an absorbable collagen velour placed in the prostatic bed. Postoperative blood loss was significantly smaller than in a control group. The gluing technique resulted in a sparing of the number of blood transfusions, a reduction in disturbances of wound healing and a shortening of postoperative hospital stay. Negative consequences of this gluing technique have not so far been observed.", "The propensity of fibrin glue to achieve ultimate control of the liver raw surface and its tolerance after hepatic resection, were evaluated by a prospective study.\n Seventy seven patients undergoing elective liver resection for benign lesions (n = 35) and malignant lesions (n = 42) including 7 with cirrhosis were studied. Randomization took place only at peritoneal closure and after completion of hemostasis and biliostasis.\n In the group with fibrin glue (n = 38), a single dose of 5 ml was applied to the liver cut surface. The appearance of the liver margin at abdominal closure was judged as dry in 34/35 (97%) patients with fibrin glue, versus 34/42 (81%) in those without (p = 0.016). Although postoperative morbidity and mortality were not different between the 2 groups, the mean total fluid drainage during the three postoperative days and bilirubin concentration were significantly lower in the group with fibrin glue; respectively 242 +/- 249 ml vs 505 +/- 666 ml and 24 +/- 21 mmoles/l vs 65 +/- 47 mmoles/l.\n Our results indicate that fibrin glue application to the hepatic stump after hepatic resection provides effective sealing with good systemic and local compatibility.", "Retention of pleural effusion after hepatectomy is an important complication that may affect the postoperative course. However, there are few reports on its pathogenesis or preventive measures. We evaluated the mechanism of the development of this complication and preventive measures against it. During the past 4-year period, hepatectomy was performed in 77 patients, of whom 64 underwent liver mobilization by transecting the hepatic ligaments. A fibrin sealant was sprayed on the cut surface of the hepatic ligaments in randomly selected 25 of the 64 patients to determine whether this application can prevent postoperative retention of pleural effusion. Post-operative pleural effusion was not observed in any patient treated by fibrin sealant spraying but was observed in 13 (30%) of the other 39 patients treated with this sealant (p < 0.05). In addition, none of the 23 patients in whom the liver was not mobilized during hepatectomy showed postoperative pleural effusion. These results suggest that severance of the hepatic ligaments is a major cause of pleural effusion, and application of a fibrin sealant to the undersurface of the diaphragm around the insertion of the liver ligaments is useful for preventing this complication.", "In contrast to the rare large-airway bronchopleural fistulas after lung resection, peripheral or alveolar air leaks (AAL) are very common, often prolong hospital stay, increase utilization of resources, and on occasion result in significant morbidity. Various adjuncts have been used in attempts to reduce AAL. One of these, the topical application of fibrin glue, has to date failed to demonstrate efficacy in small clinical trials. This study reexamines the role of fibrin glue in routine lobar and wedge pulmonary resections.\n Of 113 patients enrolled, 13 became ineligible because of intraoperative findings. The remaining 100 patients were randomly assigned to one of two groups at the conclusion of lung resection, regardless of the presence or absence of identifiable air leak. The control group received no additional intervention. The experimental group underwent application of 5 mL of fibrin glue delivered by a pressurized, aerosolized spraying mechanism. Postoperatively a blinded clinical observer recorded outcomes including the incidence and duration of AAL, prolonged AAL (PAAL), the volume of pleural drainage, the time to tube removal, and the postoperative length of stay (LOS), as well as any complications related to treatment.\n Both groups were comparable with regard to demographics, diagnoses, and procedures. Statistically significant reductions were found in the experimental group in the overall incidence of AAL (34% versus 68%, p = 0.001), mean duration of AAL (1.1 versus 3.1 days, p = 0.005), mean time to chest tube removal (3.5 versus 5.0 days, p = 0.02), and the incidence of PAAL (2% versus 16%, p = 0.015). There was no significant difference in the volume of chest tube drainage or LOS (4.6 days glue and 4.9 days control, p = 0.318). There were no complications related to the use of fibrin glue.\n Aerosolized fibrin glue appears to be safe and effective in reducing AAL. The overall incidence of AAL was reduced by 50% and PAAL occurred in only 1 treated patient (2% versus the usually reported 15%). Further studies with this and other methods are required to delineate routine versus selective use, to compare methods, and clarify cost benefit.", "We performed a prospective, randomized trial to assess the safety and efficacy of fibrin sealant in tubeless percutaneous nephrolithotomy.\n A total of 63 patients undergoing tubeless percutaneous nephrolithotomy were randomized to receive Tisseel vapor heated sealant at the end of the procedure. Fibrin sealant was instilled under direct vision in the nephrostomy tract at the end of the procedure. Patients younger than 14 years and those undergoing staged percutaneous nephrolithotomy or bilateral simultaneous percutaneous nephrolithotomy were excluded from study. Patients needing greater than 2 percutaneous tracts, those with significant bleeding or associated pyonephrosis and those with a residual stone burden were also excluded from study. The perioperative outcome in these patients (experimental group) was compared with the outcome in those undergoing tubeless percutaneous nephrolithotomy without fibrin sealant (control group).\n Fibrin sealant was instilled in 32 patients. There was no difference in the hematocrit decrease and blood transfusion requirement in the 2 groups. Patients in the experimental group experienced less postoperative pain and required less analgesia. They were discharged home 5 hours earlier than patients in the control group. However, this difference was not statistically significant. Complete stone clearance was achieved in 87.5% of patients in the experimental group and in 90.32% of controls.\n The instillation of Tisseel fibrin glue is safe for tubeless percutaneous nephrolithotomy. It is associated with less postoperative pain and a lower analgesic requirement. Additional prospective, randomized studies are required to better define its clinical role in the future." ]

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[ "Promoting breast and cervical cancer screening at the workplace: results from the Woman to Woman Study.", "Effectiveness of three community based strategies to promote screening for cervical cancer.", "Mass mailing campaigns to promote screening for cervical cancer: do they work, and do they continue to work?", "Improving uptake of cervical cancer screening in women with prolonged history of non-attendance for screening: a randomized trial of enhanced invitation methods.", "Increasing women's compliance with opportunistic cervical cancer screening: a randomized trial.", "Using nurses for preventive activities with computer assisted follow up: a randomised controlled trial.", "A randomized study of cancer screening in a family practice setting using a recall model.", "Por La Vida intervention model for cancer prevention in Latinas.", "Randomised controlled trial of the effect of evidence based information on women's willingness to participate in cervical cancer screening.", "A large population-based randomized controlled trial to increase attendance at screening for cervical cancer.", "Do personalised letters in Vietnamese increase cervical cancer screening among Vietnamese women?", "Effectiveness of a call/recall system in improving compliance with cervical cancer screening: a randomized controlled trial.", "Can health education increase uptake of cervical smear testing among Asian women?", "A randomized controlled trial of interventions to promote cervical cancer screening among Chinese women in North America.", "A randomised controlled trial of strategies to prompt attendance for a Pap smear.", "Does the offer of cervical screening with breast screening encourage older women to have a cervical smear test?", "How much does a reminder letter increase cervical screening among under-screened women in NSW?", "Computerized reminders to encourage cervical screening in family practice.", "Promoting participation in a population screening program for breast and cervical cancer: a randomized trial of different invitation strategies.", "The effect of adding Pap smear information to a mammography reminder system in an HMO: results of randomized controlled trial.", "Do tailored behavior change messages enhance the effectiveness of health risk appraisal? Results from a randomized trial.", "Prospective randomised controlled trial of methods of call and recall for cervical cytology screening.", "Effective lay health worker outreach and media-based education for promoting cervical cancer screening among Vietnamese American women.", "Effect of a cancer screening intervention conducted by lay health workers among inner-city women.", "Pap smear screening at an urban aboriginal health service: report of a practice audit and an evaluation of recruitment strategies.", "Cervical cytology screening: a comparison of two call systems.", "The impact of tailored interventions on a community health center population.", "Cervical screening in general practice.", "The safety net: a cost-effective approach to improving breast and cervical cancer screening.", "Promotion of cervical screening among nonattendees: a partial cost-effectiveness analysis.", "How reminders given to patients and physicians affected pap smear use in a health maintenance organization: results of a randomized controlled trial.", "Computer-generated physician and patient reminders. Tools to improve population adherence to selected preventive services.", "Media interventions to increase cervical screening uptake in South Africa: an evaluation study of effectiveness.", "Pap smear outreach: a randomized controlled trial in an HMO.", "Message framing and pap test utilization among women attending a community health clinic." ]

[ "This article reports findings from a peer-delivered intervention designed to increase use of breast and cervical cancer screening.\n Twenty-six worksites were randomly assigned to the intervention or comparison group. The 16-month intervention consisted of group discussions, outreach, and educational campaigns. Data were collected from a random sample of women employees stratified by age (baseline n = 2943; final n = 2747). Cross-sectional analyses were conducted to evaluate the impact of the intervention on screening behaviors.\n Relative to comparison worksites, the intervention group experienced greater increases in the percentage of women who reported a recent mammogram (7.2% vs 5.6%), clinical breast examination (5.8% vs 2.1%), and Papanicolaou (Pap) test (4.7% vs 1.9%). After worksite cluster and age strata were controlled for, the observed increase in Pap tests was significantly greater in the intervention group (odds ratio [OR] = 1.28; 95% confidence interval [CI] = 1.01, 1.62); however, differences in mammography screening rates (OR = 1.14; 95% CI = 0.90, 1.44) and clinical breast examination (OR = 1.19; 95% CI = 0.96, 1.49) were not statistically significant.\n Intervention activities produced a modest increase in cervical cancer screening, but they did not accelerate breast cancer screening rates above the observed secular trend.", "Evaluation of three potential methods for increasing Pap smear use: television media, television media combined with letter based recruitment, and television media combined with general practitioner based (GP based) recruitment.\n A trial of each intervention was carried out in three postal regions in New South Wales, Australia-a rural locality (containing about 1000 women), a country town (about 3000 women), and a major rural centre (about 10,000 women). Three control regions were selected to be demographically similar to the corresponding intervention regions.\n Outcome data on regional Pap smear rates were obtained from government health insurance claims for cervical screening, and from pathology service records. Expected Pap smear rates for the three months after the intervention were predicted from 45 pre-intervention months and were compared with observed rates for this period.\n Television media alone was associated with a significant increase in attendances for screening in one of the three regions where a trial was carried out: 13.3% in the rural centre. The media/letter based campaign was associated with a significant increase in attendances in two out of three regions: 52.7% in the rural locality, 43.2% in the rural centre. The media/GP based campaign was associated with significant increases in attendances in all three regions: 50.2% in the rural locality, 80.8% in the country town, 15.7% in the rural centre. All three interventions were associated with significant increases in the number of women attending for cervical screening above those observed in the control regions. Furthermore, these increases were not restricted to women at low risk. They were also found for older women (aged 50-69 years) and women who had not had a Pap smear within the past three years.", "Campaigns involving sending personally addressed letters to encourage women to have Pap smears increase Pap smear rates. The aim of this study was to assess whether this effect is maintained when campaigns are repeated regularly. In October 1992, a letter reminding women of the importance of screening was mailed to all women in three New South Wales postcode regions where a similar letter had been sent three years previously. The response was compared to the response in three regions receiving no earlier letter. The number of women attending for cervical screening during the three months after distribution of the letters was assessed from Health Insurance Commission claims for cervical cytology. These attendances were compared with expected attendances based on the attendance patterns over 28 pre-intervention quarters. Significant postintervention increases in attendance were observed in all three regions receiving an initial letter. However, in one region, the increase in attendances, around 1 per cent of eligible women, was not significantly greater than the increase in the control region (z = 0.15, P = 0.88). The second letter campaign had no measurable effect on attendances. No significant increase in screenings was observed in two of the towns. A significant increase was observed in one region, but this was not significantly greater than the increase in the control region (z = -0.05, P = 0.96). These results suggest that repeated direct-mail campaigns to promote screening for cervical cancer may be of no benefit. A one-off campaign may result in an increase in screenings in the short term.", "To compare the effectiveness and cost-effectiveness of three methods of inviting women with a long history of non-attendance to undergo cervical screening.\n Randomized controlled trial and cost-effectiveness analysis. In all, 1140 women were identified from routine NHS screening records as having no smear for at least 15 years and randomly allocated to receive a telephone call from a nurse, a letter from a well-known celebrity (Claire Rayner) or letter from the local NHS Cervical Screening Commissioner. Uptake of screening was measured using routine data and attributed to interventions if occurring within three months. Uptake was compared with a control group. Costs of carrying out the interventions were noted from the perspective of the NHS and cost-effectiveness, as cost per additional attender, calculated.\n Uptake following all interventions was low: telephone call (1.4, 95% confidence interval [CI] 0.38-3.6%); celebrity letter (1.8, 95% CI 0.57-4.0%); commissioner letter (4.6, 95% CI 2.5-7.7%); control group (1.8, 95% CI 0.57-4.0%). There were no significant differences between groups. Telephone intervention was not possible in a quarter of women whose numbers were unlisted. Telephone intervention was the most expensive and least effective of the interventions. The commissioner letter yielded an additional attender within three months at an incremental cost of 23.21 pounds compared with taking no action.\n Neither a telephone call from a nurse nor a letter from a celebrity to encourage attendance for cervical screening were effective or cost-effective in women with a prolonged history of non-participation in the screening programme. A letter from the local cervical screening programme commissioner resulted in a small, non-significant increase in uptake. The low cost and ease of implementation of this intervention supports further research into its use in routine practice.", "Our objective was to evaluate the efficacy and acceptability of two interventions designed to increase opportunistic cervical cancer screening. We designed a randomized trial of two interventions additional to usual care. We recruited 17 male general practitioners selected at random from the inner metropolitan region of Sydney, Australia. The patients were 202 women, between 20 and 65 years of age, eligible for a Pap smear. We allocated minimal and maximal interactional interventions to obtain consent for a Pap smear. Our main outcome measure was women's having a Pap smear during the consultation or within one month. We also measured acceptability of interventions to practitioners and women. These were our results: minimal: 55% of women had a Pap smear; maximal: 67% of women had a Pap smear; total when both approaches are combined: 61%. We conclude that brief advice is as effective as maximal persuasion in increasing women's compliance with opportunistic screening in routine consultations. Both interventions were acceptable to women. Practitioners preferred the minimal intervention. We demonstrate opportunistic screening is an effective and acceptable way to encourage women at risk to have a Pap smear.", "To assess whether an organised programme of prevention including the use of a health promotion nurse noticeably improved recording and follow up of cardiovascular risk factors and cervical smears in a general practice that had access to computerised cell and recall.\n Randomised controlled trial.\n General practice in inner London.\n All 3206 men and women aged 30-64 registered with the practice.\n The intervention group had their risk factors ascertained and followed up by the health promotion nurse and the general practitioner, whereas those in the control group were managed by the general practitioner alone.\n Recording and follow up of blood pressure and cervical smears after three years. Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations were also examined. MEASUREMENTS and\n When the trial was stopped after two years the measurements of blood pressure in the preceding five years were 93% (1511/1620) v 73% (1160/1586) (95% confidence interval for difference 17.5 to 22.7%) for intervention and control groups respectively. For patients with hypertension the figures were 97% (104/107) v 69% (80/116) (18.2 to 38.2%). For women the proportion who had had a cervical smear in the preceding three years were 76% (606/799) v 49% (392/806) (22.5 to 31.9%). Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations was also higher in the intervention group compared with the control group.\n An organised programme, which includes a nurse with specific responsibility for adult prevention, is likely to make an important contribution to recording of risk factors and follow up of those patients with known risks.", "A randomized controlled study that evaluated a recall system and patient education material by mail in 178 asymptomatic female family practice patients aged 50 to 69 years showed no effect on the proportion of patients who had cancer screening tests (P = .20) and a significant adverse effect on the mean number of tests performed (P = .05) after 4 months. In a subgroup of previous compliers (those who had one or more tests 12 months before the study), however, there was a lower proportion of patients receiving one or more tests (P = .019) with a lower mean number of tests (P = .007) than previous compliers in the control group. Recall strategies for cancer screening tests need to be more extensively studied in the United States before they are routinely adopted in family practice.", "Our goal was to describe the development and implementation of an intervention on cancer prevention for Latinas in San Diego, Calif. Thirty-six lay community workers (\"consejeras\") were recruited and trained to conduct educational group sessions. Each consejera recruited approximately 14 peers from the community to participate in the program (total number = 512). Half of the consejeras were randomly assigned to a control group, in which they participated in an equally engaging program entitled \"Community Living Skills.\" Implementation of the intervention was assessed by qualitative and quantitative methods. Preintervention and postintervention self-report information was obtained from project participants on access to health care services, cancer knowledge, preventive measures, and previous cancer-screening examinations. Base-line data suggest that lack of knowledge, costs of cancer-screening tests, and the lack of a regular health care provider are the major obstacles against obtaining cancer-screening tests. Predisposing factors, such as fear and embarrassment, also constitute barriers to getting regular cervical cancer screening. Preliminary analysis indicates that the Por La Vida intervention increases use of cancer-screening tests in comparison to a community living skills control group. Universal access to health care would remove some of the major financial barriers to cancer screening. The Por La Vida program attempts to overcome the substantial barriers by reaching out to low-income Latinas and by providing information regarding the availability, acceptability, and preventive nature of cancer-screening tests.", "To assess whether providing women with additional information on the pros and cons of screening, compared with information currently offered by the NHS, affects their intention to attend for screening.\n Randomised controlled trial. Participants were randomly assigned to receive either the control, (based on an NHS Cervical Screening Programme leaflet currently used), or the intervention leaflet (containing additional information on risks and uncertainties).\n Three general practices in Birmingham.\n 300 women aged 20 to 64 attending the practices during a one month period.\n Intention to attend for screening. Main results: 283 women (94.3%) completed the study. Fewer women in the intervention (79%) than the control group (88%) expressed intention to have screening after reading the information leaflet (difference between groups 9.2%, 95% confidence intervals (CI) 3.2% to 21.7%). The crude odds ratio (OR) and 95% CI was 0.50 (0.26 to 0.97). After adjusting for other factors, the trend persisted (OR 0.60, 95% CI 0.28 to 1.29). Having a previous Pap smear was the only significant predictor of intention to have screening (adjusted OR 2.54, 95% CI 1.03 to 6.21). Subgroup analysis showed no intervention effect in intended uptake between women at higher and lower risk of cervical cancer (p=0.59).\n Providing women with evidence based information on the risks, uncertainties, and the benefits of screening, is likely to deter some, but not differentially those at higher risk.", "Although cervical cancer is one of the potentially most preventable malignancies, it is still fairly common. In settings with established screening programs, increased compliance is important for future reduction in cervical cancer incidence, but it is presently unclear how this can be effectively achieved.\n We conducted a randomized controlled trial including all 12,240 women invited to organized screening in Sweden. To increase compliance, three successive interventions were tested: (a) modified invitation versus the standard invitation letter, (b) reminder letter to nonattenders after the first intervention versus no reminder letter, and (c) phone reminder to nonattenders after the reminder letter versus no phone reminder. We analyzed the proportion of women attending screening after each intervention and the cumulative proportion after the interventions as well as the cumulative proportions of cytologic abnormalities.\n The modified invitation did not increase attendance compared with the standard invitation letter [difference 1.3% 95% confidence interval (CI) -0.3 to 2.9]. In contrast, a reminder letter increased the proportion of women attending with 9.2% (95% CI 7.9-10.5) compared with women who did not receive a reminder letter, and a phone reminder increased the proportion of women attending with 31.4% (95% CI 26.9-35.9). Combinations of modified invitation, written reminder, and phone reminder almost doubled attendance within 12 months, and the number of detected cytologic abnormalities was more than tripled.\n Simple reminders by mail and phone can drastically increase women's participation in Papanicolaou smear screening and increase the number of detected precursor lesions and thereby save lives.", "In Australia, Vietnamese women are at greater risk of cervical cancer than other Australian women. To increase their participation in cervical screening, the Vietnamese community was exposed to a media campaign about the advantages of cervical smear screening which was delivered in Vietnamese through Vietnamese newspapers and radio. In addition, 689 Vietnamese (18-67 years) were selected from the electoral roll. They were randomly assigned to either receive a personal letter written in Vietnamese promoting cervical screening, or not. We report on the effect of the letter on smear rates. Being randomised to be sent such a letter was not associated with any increase in screening (relative rate of appropriate screening in the intervention versus the control group was 0.85, 95% CI 0.55-1.3). It is important to carefully evaluate untested health promotion interventions.", "To determine the effectiveness of a simple call/recall system in improving compliance with cervical cancer screening among women not screened in the previous 3 years.\n Prospective randomized controlled study.\n Two family medicine clinics (1 urban, 1 rural) affiliated with Memorial University of Newfoundland, St. John's.\n A sample of women aged 18-69 years who were listed as patients of the clinics but who had not had a Papanicolaou test (Pap test) within the 3 years before the start of the study. Of 9071 women listed as patients 1360 (15.0%) had not undergone screening in the previous 3 years. A random sample of 650 were selected, 209 of whom were excluded because they had had a hysterectomy, had had a recent Pap test, had moved or had records containing clerical errors. This left 441 women for the study.\n The 221 women in the intervention group were sent a letter asking them to seek a Pap test and a reminder letter 4 weeks later. The 220 in the control group were sent no letters.\n Number of women who had a Pap test within 2 months and 6 months after the first letter was sent.\n Within 2 months, more women in the intervention group than in the control group had been screened (2.8% [5/178] and 1.9% (4/208] respectively). There was also a difference between the overall proportions at 6 months (10.7% [19/178] and 6.3% [13/208] respectively). None of the differences was statistically significant.\n A letter of invitation is not sufficient to encourage women who have never or have infrequently undergone a Pap test to come in for cervical cancer screening. The effectiveness of added recruitment methods such as opportunistic screening by physicians, follow-up by telephone and the offer of a specific appointment should be evaluated.", "To determine the effects of three different methods of providing health education on the uptake of cervical smear testing among Asian women, and to evaluate the acceptability of different health education materials.\n Prospective cohort study over one year of effects of written materials by post, personal visit to give written materials, and personal visit to show a video on the uptake of smear testing. Techniques included a personally administered questionnaire.\n Leicester, a city with a large Asian population.\n 737 randomly selected Asian women aged 18 to 52 who were not recorded on the central cytology laboratory's computer as ever having had a cervical smear test. 159 declined to participate or were not contactable.\n Women were randomised into four groups: visited and shown a video (263), visited and shown a leaflet and fact sheet (219), posted a leaflet and fact sheet (131), not contacted at all (124).\n Cervical smear test recorded on computer within four months after intervention.\n 57 (37%, 26% of group) of the women visited and given leaflets and 80 (47%, 30% of group) shown the video attended for cervical smears. Only six (5%) of those who were not contacted and 14 (11%) of those sent leaflets had a smear test during the study.\n Health education interventions increased the uptake of cervical cytology among Asian women in Leicester who had never been tested. Personal visits were most effective irrespective of the health education materials used, but there was some evidence that home viewed videos may be particularly effective in one of the most hard to reach groups: Urdu speaking, Pakistani Moslems. Written translated materials sent by post were ineffective.", "North American Chinese women have lower levels of Papanicolaou (Pap) testing than other population subgroups. We conducted a randomized controlled trial to evaluate the effectiveness of two alternative cervical cancer screening interventions for Chinese women living in North America.\n Four hundred and eighty-two Pap testing underutilizers were identified from community-based surveys of Chinese women conducted in Seattle, Washington, and Vancouver, British Columbia. These women were randomly assigned to one of two experimental arms or control status. Several Chinese-language materials were used in both experimental arms: an education-entertainment video, a motivational pamphlet, an educational brochure, and a fact sheet. Women in the first experimental group (outreach worker intervention) received the materials, as well as tailored counseling and logistic assistance, during home visits by trilingual, bicultural outreach workers. Those in the second experimental group (direct mail intervention) received the materials by mail. The control group received usual care. Follow-up surveys were completed 6 months after randomization to ascertain participants' Pap testing behavior. All statistical tests were two-sided.\n A total of 402 women responded to the follow-up survey (83% response rate). Of these women, 50 (39%) of the 129 women in the outreach group, 35 (25%) of the 139 women in the direct mail group, and 20 (15%) of the 134 women in the control group reported Pap testing in the interval between randomization and follow-up data collection (P<.001 for outreach worker versus control, P =.03 for direct mail versus control, and P =.02 for outreach worker versus direct mail). Intervention effects were greater in Vancouver than in Seattle.\n Culturally and linguistically appropriate interventions may improve Pap testing levels among Chinese women in North America.", "To assess the comparative efficacy, by randomised controlled trial, of three interventions designed to encourage \"at risk\" women to have a Pap smear: an educational pamphlet; letters inviting attendance at a women's health clinic; and letters from physicians.\n Subjects at risk for cervical cancer who had not been adequately screened were identified by a random community survey and randomly allocated to one of the intervention groups or a control group. Six months after intervention implementation, a follow up survey assessed subsequent screening attendance. Self report was validated by comparison with a national screening data base.\n A significantly greater proportion of women (36.9%) within the group receiving a physician letter reported screening at follow up than in any other group (P = 0.012). The variables most strongly predicting screening attendance were: age, perceived frequency of screening required, use of oral contraceptives, and allocation to receive the physician letter intervention.\n The relative efficacy of the GP letter in prompting screening attendance shows that this strategy is worthy of further investigation. There remains a need to examine the barriers to screening for older women, and to develop tailored strategies for this population.", "The aim was to determine what effect the offer of a cervical smear test when attending for breast screening has on the uptake of cervical and breast screening.\n The study involved randomisation to compare uptake in those women invited for cervical screening in advance with their breast screening invitation (group 1) with those invited for breast screening only and then offered a smear test upon arrival for breast screening (group 2). The main outcome measure was improvement in the uptake of cervical screening among older women without detriment to the breast screening service.\n The study took place at the Northern Hospital in North Manchester.\n Participants were 2131 women aged 50-64 years invited for breast screening at the Northern Hospital in the summer of 1990.\n Overall, 54% of the women who were eligible attended for breast screening, 52% attended from group 1 and 55% from group 2. Of those attending for breast screening, 957 were eligible for cervical screening and 193 (20%) had a smear test. There was a difference in the proportion tested from each group (p < 0.001), 28% had a smear test from group 1 and 13% from group 2. Forty five percent of the 193 had not had a cervical smear for at least five years.\n The cervical screening facility did attract some women who were overdue for a smear test and who might not normally have attended for cervical screening, and there was no evidence to suggest that it had a detrimental effect on the breast screening uptake. An advanced cervical screening invitation seemed preferable to an invitation upon arrival at the breast screening unit.", "To evaluate a direct mail-out campaign to increase Pap screening rates in women who have not had a test in 48 months.\n Ninety thousand under-screened women were randomised to be mailed a 48-month reminder letter to have a Pap test (n=60,000), or not to be mailed a letter (n=30,000). Differences in Pap test rates were assessed by Kaplan-Meier survival analysis, by chi2 tests of significance between Pap test rates in letter versus no-letter groups, and by proportional hazards regression modelling of predictors of a Pap test with letter versus no-letter as the main study variable. T-tests were conducted on mean time to Pap test to assess whether time to Pap test was significantly different between the intervention and control groups.\n After 90 days following each mail-out, Pap test rates in the letter group were significantly higher than in the non-letter group, by approximately two percentage points. After controlling for potential confounders, the hazard ratio of a Pap test within 90 days of a mail-out in the letter group was 1.5 compared with 1.0 in the no-letter group. Hazard ratios of having a Pap test within 90 days decreased significantly with time since last Pap test (p<0.0001); were significantly higher than 1.0 for most non-metropolitan areas of NSW compared with metropolitan areas; and increased significantly with age (p<0.0001). Pap test hazard ratios were not associated with socio-economic status of area of residence, but the hazard ratio was significantly higher than 1.0 if the reminder letter was sent after the Christmas/New Year break. No significant differences in mean time to Pap test were found between the letter and no-letter groups.\n Being sent a reminder letter is associated with higher Pap testing rates in under-screened women.", "In a randomized trial three ways of increasing rates of cervical screening were compared for women attending a family medicine center. Working from computerized medical records, 1,587 women aged 18 to 35 years who were overdue for a screening test were included in the study. In a control group, no formal method was used to encourage patients to attend for screening, and 13.7 percent obtained a test within the trial year. In one intervention group the physician was issued a message identifying those women visiting the center for a routine appointment who were due for screening; 16.1 percent were screened. Sending a letter to patients in a second group yielded a 25.9 percent compliance rate. In a third group the practice nurse called patients on the telephone to advise them to obtain the test, and 20.0 percent complied. Reminders issued to the physician provide a low-cost, opportunistic approach to reach women who happen to visit the practice, but this approach should be supplemented by telephoning or sending a letter to those women who do not attend regularly.", "Attendance level has been identified as a major determinant of cost-effectiveness of organized screening programs. We tested the effectiveness of 4 different invitation systems in the context of an organized population screening program for cervical and breast cancer.\n Women eligible for invitation--8385 for cervical and 8069 for breast cancer screening--listed in the rosters of 43 and 105 general practitioners (GP), respectively, who had accepted to collaborate in the program, were randomized to 4 invitation groups: Group A--letter signed by the GP, with a prefixed appointment; Group B--open-ended invitation, signed by the GP, prompting women to contact the screening center to arrange an appointment; Group C--letter (same as for group A), signed by the program coordinator, with a prefixed appointment; Group D--extended letter (highlighting the benefits of early cancer detection) signed by the GP, with a prefixed appointment. Assignment to the interventions was based on a randomized block design (block=GP).\n Assuming Group A as the reference, the overall compliance with cervical cancer screening was reduced by 39% in Group B (RR=0.61; 95% CI, 0.56-0.68) and by 14% in Group C (RR=0.86; 95% CI, 0.78-0.93); no difference was observed for Group D (RR=1.03; 95% CI, 0.95-1.1). The response pattern was similar for breast screening (Group B: RR=0.71; 95% CI, 0.65-0.76; Group C: RR=0.87; 95% CI, 0.81-0.94; Group D: RR=1.01; 95% CI, 0.94-1.08).\n Personal invitation letters signed by the woman's GP, with preallocated appointments, induce a significant increase in compliance with screening. Efficiency can be ensured through the adoption of overbooking, provided that attendance levels are regularly monitored.", "While reminders can promote cancer screening in primary care, little is known about the potential interaction between multiple reminders.\n We conducted a randomized controlled trial to compare the effect of combined Pap smear plus mammogram reminders and mammogram-only reminders among 2471 women 40 years of age or older enrolled in a health maintenance organization serving a predominantly Medicaid-eligible population. Reminders included both a mailed letter for the woman and a medical record prompt.\n Intervention assignment was unassociated with differences in rates of visitation to family medicine or internal medicine or completion of mammography during the study year. Compared to women assigned to mammogram-only reminder treatment, those assigned to the combined Pap smear plus mammogram reminder intervention were more likely to visit a gynecologist (34% compared to 29%, adjusted odds ratio = 1.33, 95% confidence interval 1.08-1.63) and to complete a Pap smear (30% compared to 23%, adjusted odds ratio = 1.39, 95% confidence interval 1.07-1.89).\n In the study setting, the addition of Pap smear to mammography reminders has a procedure-specific effect, increasing gynecology visits and Pap smear use while neither increasing nor decreasing other primary care visits or mammography. We find no evidence of reinforcement or competition between these reminders.", "Health risk appraisal (HRA) remains one of the most widely used health promotion tools despite only equivocal evidence for its effectiveness. Theories of behavior change predict conventional HRA's ineffectiveness because risk information alone is seldom sufficient to change complex behaviors. In this study, a randomized trial compared the effects of feedback from an enhanced HRA with a typical HRA and a control group among adult patients from eight family medicine practices. The enhanced HRA assessed behavior-specific psychosocial factors and provided patients with computer-generated, individually-tailored behavior change information in addition to typical HRA risk feedback. Changes in seven behaviors were assessed at a 6 month follow-up. Overall, patients receiving enhanced HRA feedback were 18% more likely to change at least one risk behavior than were patients receiving typical HRA feedback or no feedback (OR = 1.18, 95% CI = 1.00, 1.39). The enhanced HRA feedback appeared to promote changes in cholesterol screening, dietary fat consumption and physical activity, but not in smoking, seat belt use, mammography and Pap smears. We conclude that the addition of theory-based, individually-tailored behavior change information may improve the effectiveness of HRA.", "To discover whether systematic methods of call and recall are more effective than a non-systematic method and to see which of the two systematic methods was more effective.\n Prospective randomised controlled trial over a year.\n One group general practice.\n 416 Women over 35 eligible for a smear test who had never had a cervical smear test or in whom a smear test was overdue (previous test more than five years before).\n One group received written invitations to have a smear taken. The second group had their notes tagged so that the doctor would remind them (when they attended for another reason) to have a smear test. No special intervention was made in the third group.\n Performance of a cervical smear test during the year of the study.\n 32% (45/140) of the screened group, 27% (39/142) of the tagged group, and 15% (20/134) of the control group had a smear test during the year. The percentage of women having a smear test in the screened group was not significantly different from that in the tagged group, but the percentages in the two groups were significantly different from that in the control group. Whether a woman had had a previous smear test significantly affected the uptake of the invitation to have a smear test independently of the method of invitation.\n The systematic methods of call and recall were more effective than a non-systematic method. There was no significant difference between the two systematic methods (sending letters or tagging the notes) at one year.", "We sought to promote cervical cancer screening among Vietnamese American women in Santa Clara County, Calif.\n In 2001-2004, we recruited and randomized 1005 Vietnamese American women into 2 groups: lay health worker outreach plus media-based education (combined intervention) or media-based education only. Lay health workers met with the combined intervention group twice over 3 to 4 months to promote Papanicolaou (Pap) testing. We used questionnaires to measure changes in awareness, knowledge, and Pap testing.\n Testing increased among women in both the combined intervention (65.8% to 81.8%; P<.001) and media-only (70.1% to 75.5%; P<.001) groups, but significantly more in the combined intervention group (P=.001). Among women never previously screened, significantly more women in the combined intervention group (46.0%) than in the media-only group (27.1%) obtained tests (P<.001). Significantly more women in the combined intervention group obtained their first Pap test or obtained one after an interval of more than 1 year (became up-to-date; 45.7% to 67.3%, respectively; P<.001) than did those in the media-only group (50.9% to 55.7%, respectively; P=.035).\n Combined intervention motivated more Vietnamese American women to obtain their first Pap tests and to become up-to-date than did media education alone.", "We conducted a randomized controlled trial to determine if an in-home educational intervention conducted by lay health workers (LHWs) could increase adherence among low-income, inner-city, African-American women to breast and cervical cancer screening schedules.\n We recruited 321 African-American women from diverse inner-city sources. After baseline interviews, they were randomly assigned to either the intervention (n = 163) or the control (n = 158) group. Those in the intervention group were visited in their homes up to three times by LHWs who provided a culturally sensitive educational program that emphasized the need for screening.\n Ninety-three (93) women in the intervention group and 102 in the control group completed the postintervention interview. For Pap smears, the increase in screening was similar in both groups. For clinical breast exams (CBEs), however, there was a modest increase in the intervention group. The improvement was greatest for mammography, for which there was a 10% to 12% increase. Among women who were not on recommended schedules at baseline, the improvement was substantial and greater in the intervention group.\n LHWs' intervention appeared to improve the rate at which inner-city women obtained CBEs and mammograms, but had no effect on Pap smears. A high attrition rate weakened our ability to make conclusive statements about the exact impact of the intervention.", "A culturally appropriate women's health service was established at an Aboriginal community-controlled health service in Darwin in 1994. An initial file audit found that 48% of included women had ever been screened with a Pap smear and 37% of women were considered to have been adequately screened. The enhancement of opportunistic screening by file tagging had a modest effect on screening coverage over a 12-month period for women who attended the health service. The proportion of these women who were adequately screened increased from 43% to 48% and of those ever screened increased from 54% to 62%. A randomised trial of recruitment interventions including personal approach, letter and control groups was subsequently performed for women for whom Pap smears were overdue or not recorded. The impact of both interventions on the number of Pap smears performed was low, with 7% of women in the personal approach group, 2% of women in the letter group and no women in the control group having Pap smears during the three-month follow-up period. Low rates of abnormalities were observed for women having Pap smears over a two-year period. The minimal effect of a formal reminder system and letters at this urban Aboriginal health service has resulted in a re-orientation of activities towards strengthening opportunistic screening and the continued promotion of Pap smears in a range of clinic and community settings. It is important to place Pap smear screening in the context of other social, economic and health priorities for Aboriginal women and health workers.", "nan", "We conducted a 4-year randomized study in a community health center that serves primarily low income Blacks in Durham, North Carolina. Patients (1318 at baseline) were assigned randomly to one of three study groups: provider prompting intervention alone, provider prompting and tailored print materials or the previous group and tailored telephone counseling. The purpose of the study was to determine whether increasingly intensive, tailored print and telephone interventions also were increasingly effective in promoting adherence to mammograms, Pap tests and overall cancer screening compliance. Thus, the combination of tailored print interventions (print and telephone) should have been more effective than the provider prompting intervention alone, or the print intervention and prompting combination. This is one of the few studies to examine a measure of overall cancer screening compliance and to assess the benefit of combinations of tailored interventions in promoting adherence to cancer screening. Patients gave extremely high ratings to the interventions. At the bivariate level, we found a significant effect of the most intensive group (provider prompting intervention, tailored print communications and tailored telephone counseling) on Pap test compliance (P = 0.05) and borderline significance at the multivariate level (P = 0.06) as well on overall screening compliance (P = 0.06). There was not a significant effect on mammography, probably because a majority of the patients were receiving regular mammograms. We also found some important subgroup differences. For example, a larger proportion of women reported Pap tests in the tailored print and counseling group when they believed the materials were 'meant for me.' These results show that a combination of tailored interventions may have potential for reaching the women who have too often been labeled the 'hard to reach.'", "This study examined the effect of three interventions for encouraging women to have a Pap smear in a general practice: tagging the medical record to remind the doctor to offer a Pap smear, sending an invitation to make an appointment for a Pap smear, and sending an invitation with an appointment to attend for a Pap smear at a special screening clinic staffed by women. The study took place in a university general practice at Lockridge, near Perth. A computerised practice age-sex register provided 2139 women in the age range 36 to 69 inclusive. Of these, 757 were eligible for inclusion in the study and were allocated randomly to one of three intervention groups or a control group. In total, 177 women had a Pap smear during the study. Significantly more Pap smears were taken for the appointment-letter and letter-only groups than the control group (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.34 to 3.57, and OR 1.67, CI 1.01 to 2.77 respectively), but there was no significant difference between the tagged-notes and the control groups. Women who attended the screening clinic rated the experience positively. Attendance, however, was inadequate for the clinic's viability in a private practice.", "The purposes of the study were (1). to assess the cost-effectiveness of three interventions to deliver breast and cervical cancer screening to women unscreened for >or=3 years and (2). to determine the relation of an invasive cervical cancer diagnosis to the interval since the last true screening test.\n In a randomized trial, women were randomly assigned to (1). usual care, (2). letter plus follow-up letter, (3). letter plus follow-up phone call, (4). phone call plus follow-up phone call. Screening within 12 weeks was the outcome. A 5-year retrospective review of cervical cancer cases and screening histories was done.\n The 8% of women not screened for >or=5 years had 62% of the invasive cervical cancer cases. Mammography outreach led to screening in 10%, 24%, 51%, and 50% of controls, letter/letter, letter/phone, and phone/phone interventions groups, respectively. Cervical cancer screening outreach led to screening in 17%, 22%, 54%, and 50% of the respective groups. Letter reminders alone produced fewer tests at substantially higher costs than did personalized telephone notification.\n For cervical cancer, only 1 person in 12 was not screened in the preceding 5 years, but these accounted for nearly two thirds of invasive cancers. Aggressive outreach to the rarely screened is an important part of screening programs. Letter reminder, followed by a telephone appointment call, was the most cost-effective approach to screening rarely screened women. Lack of accurate information on prior hysterectomy adds substantial unnecessary costs to a screening reminder program.", "Measures to increase attendance rate in cervical screening programmes have been suggested, but few have been evaluated in terms of value for money. The aim of this study was to describe the cost-effectiveness of a resource-intensive intervention to promote attendance at cervical screening among women with no registered cervical smear during the last 5 years. Among all 56 644 women (28-65 years) in Kalmar County, January 2004, a total of 6565 women had no registered cervical smear during the last 5 years. From this population, 400 women were randomly selected to a study group and another 400 women to a control group. The intervention was composed of a variety of efforts intended to promote attendance at cervical screening. We included, for example, all costs for identifying the women, sending out invitation letters, making phone calls and helping to make arrangements. Data on registered cervical smears at follow-up were collected from a data register within 1 year. In the study group, 118 women had a registered cervical smear compared with 74 in the control group (P=0.000). In the study group, the cost per cervical smear taken was 66.87 euro compared with 16.63 euro in the ordinary screening programme. The incremental cost per additional registered cervical smear was calculated at 151.36 euro in an area with high coverage, efforts to promote attendance at cervical screening were related to high costs per extra cervical smear gained and is not considered as reasonable from a cost-effectiveness perspective.", "Despite its effectiveness as a method of controlling cervical carcinoma, the use of Pap smear testing remains incomplete, and its promotion in the primary care setting provides an important opportunity for intervention.\n The authors conducted a randomized controlled trial that involved three sites of a health maintenance organization (HMO) serving an urban minority population. Their aim was to evaluate the impact of reminders given to patients and physicians on site visitation by patients and Pap smear use. Eligible women (n=5801) were randomly assigned to 1 of 4 intervention combinations (in which reminders were given to either the patient or the physician, to both, or to neither). If they were ineligible for patient reminder intervention, patients were randomized only to physician reminder intervention (the presence or absence of it). The letter of reminder mailed to the patient invited women due for Pap smears to visit the HMO site, and the reminder for physicians was a medical record notice that a Pap smear was due. Logistic and survival analyses were used to investigate the correlation of intervention status with visitation, interval of time to a visit, and Pap smear use.\n In the primary intent-to-treat analysis, there was no significant effect of either patient or physician reminder interventions on rates of visitation or Pap smear completion. The secondary efficacy analyses demonstrated no overall effect of either patient or physician reminders, but effects among subgroups of women at individual HMO sites were noted. At Site 3, there was an apparent increase in time to the next visit among the subgroup of women with a chronic illness (16 weeks with intervention vs. 9 weeks without). With the physician reminder, the odds that a Pap smear would be given during the study year were increased among women without a previous Pap smear at Site 1 (adjusted odds ratio=1.39) and those with a chronic illness at Site 2 (adjusted odds ratio=3.38).\n Reminders given to patients and physicians had a limited impact on visitation by patients to the HMO sites or Pap smear completion. Although some subgroups of women may benefit, the authors also observed a possibly unfavorable impact among other subgroups. These results emphasize the importance of identifying more effective interventions, targeting them to women most likely to benefit, and not overlooking the possibility that preventive intervention will have an unanticipated adverse effect.", "Despite an emerging consensus on appropriate preventive services, a minority of patients receive them. A study was undertaken to assess the impact of computer-generated reminders to adult patients, their physicians, or both patients and physicians on adherence to five recommended preventive services: cholesterol measurements, fecal occult blood testing, mammography, Papanicolaou smears, and tetanus immunization. During the academic year 1988-1989, all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were randomized by practice group into one of four study groups: control, physician reminders, patient reminders, and both physician and patient reminders. Adherence was defined in community-oriented terms: the percentage of patients within each group who had received the preventive service in the recommended interval. During the study period, adherence to four of the five preventive services increased significantly, with the largest increases in the physician and patient reminder group: cholesterol measurements increased from 19.5% to 38.1%, fecal occult blood testing 9.3% to 27.0%, mammography 11.4% to 27.1%, and tetanus immunization 23.4% to 35.4% (for each increase, P less than .0001, McNemar's chi-square test). In general, increases were greater in blacks and in patients with any form of insurance coverage. Computer-based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care settings.", "Successful cervical cancer prevention depends on reaching, screening and treating women with pre-invasive disease. We aimed to evaluate the effectiveness of two media interventions-a photo-comic and a radio-drama-in increasing cervical screening uptake. A randomized controlled trial compared a photo-comic on cervical cancer screening with a placebo comic. One month after the comics were distributed a radio-drama paralleling the photo-comic was broadcast on the community radio station and a retrospective evaluation was carried out. The trial was set in Khayelitsha, a peri-urban squatter community near Cape Town, South Africa. A random sample consisted of 658 women between the ages of 35 and 65 years, from a stratified sample of census areas. The main outcome measure was self-reported cervical screening uptake 6 months after distribution of the comics. Seven percent (18 of 269) of women who received the intervention photo-comic reported cervical screening during the 6 months follow-up, compared with 6% (25 of 389) of controls (P = 0.89). Women who recalled hearing the radio-drama were more likely to report attending screening (nine of 53, 17%) than those who did not (19 of 429, 4%; P < 0.001). We conclude that the photo-comic was ineffective in increasing cervical screening uptake in this population. The radio-drama may have had more impact, but only a minority of women recalled being exposed to it. Future research must concentrate not only on achieving high level of exposure to health messages, but also on investigating the links between exposure and action.", "nan", "In a randomized experiment, women (N = 441) watched either a loss- or gain-framed video emphasizing the prevention or detection functions of the Pap test to test the hypothesis that loss- and gain-framed messages differentially influence health behaviors depending on the risk involved in performing the behavior. As predicted, loss-framed messages emphasizing the costs of not detecting cervical cancer early (a risky behavior) and gain-framed messages emphasizing the benefits of preventing cervical cancer (a less risky behavior) were most persuasive in motivating women to obtain a Pap test." ]

[ "9103739", "17350966", "6470293", "10784079", "3143750", "11473908", "18563473", "17076751", "21035616", "15028546" ]

[ "Treating children with early-onset conduct problems: a comparison of child and parent training interventions.", "Parenting intervention in Sure Start services for children at risk of developing conduct disorder: pragmatic randomised controlled trial.", "Randomized trial of two parent-training programs for families with conduct-disordered children.", "Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment.", "Self-administered videotape therapy for families with conduct-problem children: comparison with two cost-effective treatments and a control group.", "Multicentre controlled trial of parenting groups for childhood antisocial behaviour in clinical practice.", "Treatment of oppositional defiant and conduct problems in young Norwegian children : results of a randomized controlled trial.", "Randomised controlled trial of a parenting intervention in the voluntary sector for reducing child conduct problems: outcomes and mechanisms of change.", "A randomized controlled effectiveness trial of parent management training with varying degrees of therapist support.", "Treating children with early-onset conduct problems: intervention outcomes for parent, child, and teacher training." ]

[ "Families of 97 children with early-onset conduct problems, 4 to 8 years old, were randomly assigned to 1 of 4 conditions: a parent training treatment group (PT), a child training group (CT), a combined child and parent training group (CT + PT), or a waiting-list control group (CON). Posttreatment assessments indicated that all 3 treatment conditions had resulted in significant improvements in comparison with controls. Comparisons of the 3 treatment conditions indicated that CT and CT + PT children showed significant improvements in problem solving as well as conflict management skills, as measured by observations of their interactions with a best friend; differences among treatment conditions on these measures consistently favored the CT condition over the PT condition. As for parent and child behavior at home, PT and CT + PT parents and children had significantly more positive interactions, compared with CT parents and children. One-year follow-up assessments indicated that all the significant changes noted immediately posttreatment had been maintained over time. Moreover, child conduct problems at home had significantly lessened over time. Analyses of the clinical significance of the results suggested that the combined CT + PT condition produced the most significant improvements in child behavior at 1-year follow-up.", "To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder.\n Pragmatic randomised controlled trial using a block design with allocation by area.\n Eleven Sure Start areas in north and mid-Wales.\n 153 parents from socially disadvantaged areas, with children aged 36-59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory. Participants were randomised on a 2:1 basis, 104 to intervention and 49 to remaining on the wait listing (control). Twenty (13%) were lost to follow-up six months later, 18 from the intervention group.\n The Webster-Stratton Incredible Years basic parenting programme, a 12 week group based intervention.\n Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home. Parents' self reported parenting competence, stress, and depression. Standardised and well validated instruments were used throughout.\n At follow-up, most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group. The intention to treat analysis for the primary outcome measure, the Eyberg child behaviour inventory, showed a mean difference between groups of 4.4 points (95% confidence interval 2.0 to 6.9, P<0.001) on the problem scale with an effect size of 0.63, and a mean difference of 25.1 (14.9 to 35.2, P<0.001) on the intensity scale with an effect size of 0.89.\n This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff. It has influenced policy within Wales and provides lessons for England where, to date, Sure Start programmes have not been effective.\n ISRCTN46984318.", "nan", "Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive, hyperactive, impulsive, and inattentive behavior. These \"disruptive\" children were randomly assigned to four treatment conditions lasting the kindergarten school year: no treatment, parent training only, full-day treatment classroom only, and the combination of parent training with the classroom treatment. Results showed that parent training produced no significant treatment effects, probably owing largely to poor attendance. The classroom treatment produced improvement in multiple domains: parent ratings of adaptive behavior, teacher ratings of attention, aggression, self-control, and social skills, as well as direct observations of externalizing behavior in the classroom. Neither treatment improved academic achievement skills or parent ratings of home behavior problems, nor were effects evident on any lab measures of attention, impulse control, or mother-child interactions. It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening, it may not be a useful approach to treating the home and community behavioral problems of such children. The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children. Even so, most treatment effects were specific to the school environment and did not affect achievement skills. These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions.", "nan", "To see whether a behaviourally based group parenting programme, delivered in regular clinical practice, is an effective treatment for antisocial behaviour in children.\n Controlled trial with permuted block design with allocation by date of referral.\n Four local child and adolescent mental health services.\n 141 children aged 3-8 years referred with antisocial behaviour and allocated to parenting groups (90) or waiting list control (51).\n Webster-Stratton basic videotape programme administered to parents of six to eight children over 13-16 weeks. This programme emphasises engagement with parental emotions, rehearsal of behavioural strategies, and parental understanding of its scientific rationale.\n Semistructured parent interview and questionnaires about antisocial behaviour in children administered 5-7 months after entering trial; direct observation of parent-child interaction.\n Referred children were highly antisocial (above the 97th centile on interview measure). Children in the intervention group showed a large reduction in antisocial behaviour; those in the waiting list group did not change (effect size between groups 1.06 SD (95% confidence interval 0.71 to 1.41), P<0.001). Parents in the intervention group increased the proportion of praise to ineffective commands they gave their children threefold, while control parents reduced it by a third (effect size between groups 0.76 (0.16 to 1.36), P=0.018). If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16%.\n Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions. Follow up is needed to see if the children's poor prognosis is improved and criminality prevented.", "The efficacy of the Incredible Years parent training and child therapy programs was examined in a randomized controlled study including 127 Norwegian children aged 4-8 years. Children diagnosed with oppositional defiant disorder (ODD) or conduct disorder (CD) were randomized to parent training (PT), parent training combined with child therapy (PT + CT), or a waiting-list control condition (WLC). Assessments were carried out at baseline, posttreatment and at a one-year follow-up using standardized measures and a semi-structured interview. Both active treatment conditions reduced child conduct problems posttreatment as opposed to the WLC, while differences between the two treatment conditions were small and nonsignificant. About two thirds of the treated children functioned within normal variation after treatment, and the same proportion no longer received an ODD diagnosis at the one-year follow-up. Parental use of positive strategies increased after treatment, and the use of harsh and inconsistent discipline decreased as did mother experience of stress. The outcome of this study emphasizes the importance of offering parent training to young children with severe conduct problems exhibited at home. The findings and usefulness of the Incredible Years program in the present Norwegian replication study further support and extend positive outcomes of previous controlled trials conducted primarily in Anglo-Saxon countries.", "To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children.\n Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems, aged 2-9, primarily low-income families, randomised to treatment vs. 6-month wait-list group. Retention was 93% at 6 months, 90% at 18 months. Interventions--Webster-Stratton Incredible Years video-based 14-week group programme, teaches cognitive-behavioural principles for managing behaviour, using a collaborative, practical, problem-solving approach. Primary outcomes--child problem behaviour by parent-report (Eyberg) and home-based direct observation; secondary outcomes--observed positive and negative parenting; parent-reported parenting skill, confidence and depression.\n Post-treatment improvements were found in child problem behaviour, by parent-report (effect size (ES) .48, p = .05) and direct observation (ES .78, p = .02); child independent play (ES .77, p = .003); observed negative (ES .74, p = .003) and positive (ES .38, p = .04) parenting; parent-reported confidence (ES .40, p = .03) and skill (ES .65, p =.01), using ANCOVA to control for baseline scores. Maternal depression did not change. Consumer satisfaction was high. At 18-month follow-up, although no randomised comparison was possible, changes appeared to maintain, with no significant change toward baseline level on any measure. Change in observed positive parenting appeared to mediate change in child problem behaviour (p < .025).\n Findings suggest that a group-based cognitive-behavioural parenting programme, delivered by well-trained and supervised staff, can be effective in a community voluntary-sector setting, for reducing conduct problems and enhancing parenting skills. Change in parenting skill appears to be a key mechanism for change in child behaviour. Findings have implications for feasibility of translating evidence-based programmes, even for clinically-referred conduct problems, into less specialised community settings, likely to have lower costs and be more accessible for families.", "This study examined the effectiveness of a Swedish parent management training (PMT) intervention for parents of children aged 3 to 10 within the context of regular social service. Self-referred parents of 159 children (aged 3 to 10) with conduct problems were randomly assigned to either 11 practitioner-assisted group sessions (PMT-P), or a single instructional workshop followed by self-administration of the training material (PMT-S), or a waitlist control group. Intent-to-treat analyses showed that both PMT-P and PMT-S improved parent competence and reduced child conduct problems compared to the waitlist at posttest. Both training conditions showed further significant improvements at the 6-month follow-up. In direct comparison, PMT-P was superior to PMT-S on measures of child conduct problems at both posttest and follow-up. Improvement in child conduct was mediated by improvement in parent competencies and homework fidelity. The findings in this study have implications for large-scale dissemination of parent management training through different means of delivery.\n Copyright © 2010. Published by Elsevier Ltd.", "Families of 159, 4- to 8-year-old children with oppositional defiant disorder (ODD) were randomly assigned to parent training (PT); parent plus teacher training (PT + TT); child training (CT); child plus teacher training (CT + TT); parent, child, plus teacher training (PT + CT + TT); or a waiting list control. Reports and independent observations were collected at home and school. Following the 6-month intervention, all treatments resulted in significantly fewer conduct problems with mothers, teachers, and peers compared to controls. Children's negative behavior with fathers was lower in the 3 PT conditions than in control. Children showed more prosocial skills with peers in the CT conditions than in control. All PT conditions resulted in less negative and more positive parenting for mothers and less negative parenting for fathers than in control. Mothers and teachers were also less negative than controls when children received CT. Adding TT to PT or CT improved treatment outcome in terms of teacher behavior management in the classroom and in reports of behavior problems." ]

[ "19281585", "19389793", "17138770" ]

[ "Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial.", "Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial.", "Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial." ]

[ "To evaluate the effect of low-dose mifepristone on leiomyoma-related symptoms, uterine and leiomyoma in women with symptomatic leiomyomata.\n In a double-blind placebo-controlled trial, 40 patients with symptomatic leiomyoma and normal endometrial histology were randomised to receive 10 mg mifepristone (group 1) or placebo (group 2) daily for three months. Leiomyoma-related symptoms, uterine, leiomyoma and largest leiomyoma volumes were assessed at baseline and every month for three months. Endometrial biopsy was repeated at the end of therapy.\n Significant change was noticed between the two groups for mean menstrual blood loss (MBL) by first month. Menstrual blood loss declined by 94.8% in group 1 at three months and 84.2% patients attained amenorrhoea in this group. In group 1 complete relief of dysmenorrhoea occurred in significant number of women (80%) but only 33% patients got rid of pelvic pain. There was no change in these symptoms in group 1 Backache, urinary complaints and dyspareunia were not relieved in either group. Uterine, leiomyoma and largest leiomyoma volume declined by 26-32% in group 1 as compared to none in group 2, and this difference was statistically significant only by the end of the third month of therapy. Mean haemoglobin increased from 9.5 to 11.2 g/dL in group 1. In group 1, at the end of therapy, 63.1% of patients had endometrial hyperplasia without atypia.\n Ten milligrams mifepristone for three months is effective in reducing MBL, increasing haemoglobin and reducing uterine and leiomyoma volume with side-effect of endometrial hyperplasia.", "Uterine leiomyomas are widely prevalent and frequently cause menorrhagia. The major therapeutic option today is hysterectomy. Medical options are of highest interest.\n A total of 30 women with uterine leiomyomas scheduled for surgical intervention were randomized to receive either 50 mg mifepristone or placebo every other day during 3 months prior to surgery. Uterine blood flow and leiomyoma volume were evaluated once a month until surgery. Endometrial biopsies were obtained prior to and at end of treatment. Relevant biochemistry, symptoms and bleeding were recorded. Primary outcome was reduction in uterine leiomyoma size.\n There was a significant percentual decrease (P = 0.021) in the total leiomyoma volume in the mifepristone-treated group, -28 (-48, -8) % (mean +/- 0, 95 confidence interval), compared with the control group values 6 (-13, 25) %. Mifepristone treatment significantly reduced the bleeding days (P = 0.001) and increased serum haemoglobin values (P = 0.046). Serum cortisol levels remained unchanged, while a mild increase in serum androgens was noted. Endometrial biopsies showed no premalignant changes or changes in mitotic indices.\n Mifepristone may offer an effective treatment option for women with uterine leiomyoma and the associated pronounced uterovaginal bleeding. Clinical Trials identifier: www.clinicaltrials.gov: NCT00579475.", "To assess the effect of low-dose mifepristone on quality of life, pain, bleeding, and uterine size among women with symptomatic leiomyomata.\n Forty-two women with symptomatic uterine leiomyomata and uterine volume of 160 mL or more were randomized to mifepristone, 5 mg daily, or placebo for 26 weeks. Quality of life (Uterine Fibroid Symptoms Quality of Life Questionnaire and Medical Outcomes Study 36-Item Short Form survey) and uterine and leiomyoma size (ultrasonography) were assessed at baseline, and at 1 month, 3 months, and 6 months of treatment. Bleeding (daily logs and pictorial charts) and pain (McGill Pain Questionnaire) were assessed monthly. Endometrial pathology was assessed at baseline and 6 months.\n Forty-two women were randomized; 37 women completed all 6 months. Women randomized to mifepristone showed an improvement in leiomyoma-specific quality of life. Forty-one percent became amenorrheic, rates of anemia improved, and adjusted uterine size was reduced by 47%. Compared with the placebo group, improvements in these outcomes in the treatment group were significantly greater (P<.05 to .001). There were no significant differences in adverse effects between the groups. No endometrial hyperplasia was noted in any participant.\n Low-dose mifepristone improves leiomyoma-specific quality of life and reduces leiomyoma size among women with symptomatic leiomyomata.\n ClinicalTrials.gov www.clinicaltrials.gov NCT00133705\n I." ]

[ "11080399", "11967670", "18418653" ]

[ "Hand-assisted laparoscopic surgery vs standard laparoscopic surgery for colorectal disease: a prospective randomized trial. HALS Study Group.", "Prospective randomized trial comparing conventional laparoscopic colectomy with hand-assisted laparoscopic colectomy: applicability, immediate clinical outcome, inflammatory response, and cost.", "Hand-assisted laparoscopic vs. laparoscopic colorectal surgery: a multicenter, prospective, randomized trial." ]

[ "We compare the use of the HandPort(TM)device in hand-assisted laparoscopic surgery (HALS) to standard laparoscopic surgery (SLS) in the treatment of colorectal disease.\n A prospective, randomized, multicenter study was conducted with the participation of 10 advanced laparoscopic surgeons. Forty patients with indications for elective resection of benign colorectal disease or incurable malignant disease were randomized to one of the two treatment arms (22 HALS, 18 SLS). Main outcome measures included operative time, blood loss, HandPort(TM) performance, postoperative pain, time to oral intake, return of bowel function, length of stay, morbidity, and functional recovery.\n The patients in each group were similar with regard to age, sex, weight, diagnosis, coexisting medical disease, and preoperative functional status. Operative time was comparable for hand-assisted laparoscopy (152 +/- 66 min) and standard laparoscopy (141 +/- 54 min) (p = 0.58). Incision length for specimen extraction/bowel anastomosis was similar (HALS 7.4 cm vs SLS 7.0 cm). Three of 22 HALS cases (14%) were converted, as compared with four of 18 (22%) in the laparoscopy group (p = 0.68). Return of bowel function occurred by the 3rd postoperative day for the majority of patients in both groups (HALS 77%, SLS 78%). There was no difference in length of stay (HALS 7.0 days [range, 2-12] vs SLS 6.0 days [range, 2-10], p = 0.25). Severity of postoperative pain and rate of functional recovery were equivalent. One major complication occurred in each group. There were three wound infections in the laparoscopy group. No patient required reoperation, and there were no deaths.\n Hand-assisted laparoscopic surgery is safe and effective for benign and noncurative colorectal resection. As compared to standard laparoscopic surgery, hand-assisted laparoscopy retains the benefits of minimally invasive surgery and may allow the surgeon to perform complex operations more easily.", "Hand-assisted laparoscopic surgery (HALS) represents a useful alternative to conventional laparoscopic surgery (LS). Its potential advantages--(a quicker, safer procedure and less need to convert to open surgery) are due to the recovery of tactile feedback. However, HALS requires the performance of a mini-laparotomy when surgery commences, and the wound is stretched and compressed throughout the procedure. In addition, it is associated with a more intense manipulation of the intraabdominal viscera. All of these factors increase the surgical trauma, it is not known whether HALS maintains the minimally invasive characteristics of conventional LS. Therefore, we set out to study the applicability, immediate clinical outcome, inflammatory response, and cost of HALS compared with conventional LS using colectomy as a model.\n We performed a prospective randomized trial comparing laparoscopic-assisted colectomy with HAL colectomy. The aims of the study were to assess (a) perioperative features, including time, advantages, and conversion; (b) the patient's immediate clinical response, including recovery of bowel sounds, refeeding time, postoperative pain, local and general morbidity, and hospital stay; (c) the effect on the inflammatory response, using interleukin-6 (ILG) and C-reactive protein (CRP) measurements; (d) oncological issues, including intraoperative cytology and features of the specimen; and (d) the relative costs of the two procedures.\n A total of 54 patients were enrolled in the study, 27 laparoscopic and 27 HALS. The operative times were similar, but HALS was associated with a far lower conversion rate--7% vs 23%. Immediate clinical outcomes, oncological features, and costs were similar for the two procedures, but HALS was associated with a significantly greater increase in IL6 and CRP than the conventional laparoscopic procedure.\n This comparative study shows that HALS simplifies difficult intraoperative situations, reducing the need for conversion. Although it is a more aggressive procedure, HALS preserves the features of a minimally invasive approach, maintains all of the oncological features of conventional laparoscopic surgery, and does not increase the cost. HALS should therefore be considered as a useful adjunct when difficult situations arise during conventional laparoscopic colectomy.", "This study was designed to compare short-term outcomes after hand-assisted laparoscopic vs. straight laparoscopic colorectal surgery.\n Eleven surgeons at five centers participated in a prospective, randomized trial of patients undergoing elective laparoscopic sigmoid/left colectomy and total colectomy. The study was powered to detect a 30-minute reduction in operative time between hand-assisted laparoscopic and straight laparoscopic groups.\n There were 47 hand-assisted patients (33 sigmoid/left colectomy, 14 total colectomy) and 48 straight laparoscopic patients (33 sigmoid/left colectomy, 15 total colectomy). There were no differences in the patient age, sex, body mass index, previous surgery, diagnosis, and procedures performed between the hand-assisted and straight laparoscopic groups. Resident participation in the procedures was similar for all groups. The mean operative time (in minutes) was significantly less in the hand-assisted laparoscopic group for both the sigmoid colectomy (175 +/- 58 vs. 208 +/- 55; P = 0.021) and total colectomy groups (time to colectomy completion, 127 +/- 31 vs. 184 +/- 72; P = 0.015). There were no apparent differences in the time to return of bowel function, tolerance of diet, length of stay, postoperative pain scores, or narcotic usage between the hand-assisted laparoscopic and straight laparoscopic groups. There was one (2 percent) conversion in the hand-assisted laparoscopic group and six (12.5 percent) in the straight laparoscopic group (P = 0.11). Complications were similar in both groups (hand-assisted, 21 percent vs. straight laparoscopic, 19 percent; P = 0.68).\n In this prospective, randomized study, hand-assisted laparoscopic colorectal surgery resulted in significantly shorter operative times while maintaining similar clinical outcomes as straight laparoscopic techniques for patients undergoing left-sided colectomy and total abdominal colectomy." ]

[ "10362181" ]

[ "The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes." ]

[ "The purpose of this study was to assess safety and efficacy of enhanced external counterpulsation (EECP).\n Case series have shown that EECP can improve exercise tolerance, symptoms and myocardial perfusion in stable angina pectoris.\n A multicenter, prospective, randomized, blinded, controlled trial was conducted in seven university hospitals in 139 outpatients with angina, documented coronary artery disease (CAD) and positive exercise treadmill test. Patients were given 35 h of active counterpulsation (active CP) or inactive counterpulsation (inactive CP) over a four- to seven-week period. Outcome measures were exercise duration and time to > or =1-mm ST-segment depression, average daily anginal attack count and nitroglycerin usage.\n Exercise duration increased in both groups, but the between-group difference was not significant (p > 0.3). Time to > or =1-mm ST-segment depression increased significantly from baseline in active CP compared with inactive CP (p = 0.01). More active-CP patients saw a decrease and fewer experienced an increase in angina episodes as compared with inactive-CP patients (p < 0.05). Nitroglycerin usage decreased in active CP but did not change in the inactive-CP group. The between-group difference was not significant (p > 0.7).\n Enhanced external counterpulsation reduces angina and extends time to exercise-induced ischemia in patients with symptomatic CAD. Treatment was relatively well tolerated and free of limiting side effects in most patients." ]

[ "12780967", "11029326", "9698957" ]

[ "Multicenter, randomized, controlled study of porcine surfactant in severe respiratory syncytial virus-induced respiratory failure.", "Exogenous surfactant supplementation in infants with respiratory syncytial virus bronchiolitis.", "Porcine-derived surfactant treatment of severe bronchiolitis." ]

[ "OBJECTIVE: Recently, natural exogenous surfactant replacement has been used in experimental models and clinical trials for the treatment of severe respiratory syncytial virus (RSV) disease. The present study was aimed at verifying this hypothesis and confirming the results of our previous pilot study by assessing the effect of surfactant treatment in mechanically ventilated infants with severe RSV-induced respiratory failure. DESIGN: Multicenter, randomized, controlled study. SETTING: Six pediatric intensive care units staffed by full-time intensive care physicians. PATIENTS: A total of 40 infants (20 treated and 20 controls) with RSV-induced respiratory failure requiring conventional mechanical ventilation (CMV) were randomly assigned to either exogenous surfactant (treated group) or conventional treatment (control group) over a 1-yr period. INTERVENTIONS: Fifty milligrams per kilogram of body weight of porcine-derived natural surfactant (Curosurf) was administered. The drug was instilled by means of a syringe attached to a small suction catheter inserted into the endotracheal tube down to its tip, momentarily disconnecting the patient from CMV. Main Outcome Measures: The assessment consisted of the following outcome variables: duration of CMV, length of intensive care unit stay, gas exchange, respiratory mechanics, re-treatment need, complications, and mortality. RESULTS: The two groups were similar with regard to demographics, Pediatric Risk of Mortality scores, and baseline Pao(2)/Fio(2), Paco(2), and ventilator settings. A marked increase in Pao(2)/Fio(2) and decrease in Paco(2) were observed in the treated group after surfactant administration. Hemodynamic parameters remained unchanged throughout the study period. Peak inspiratory pressure and static compliance were similar at baseline in the two groups. A decrease in peak inspiratory pressure and increase in static compliance were observed in the treated group after surfactant administration. Among surfactant-treated patients, 15 received the treatment within 24 hrs of admission, whereas the remainder (five patients) were treated later. Among children who were treated later, three needed an additional dose of surfactant. None of the children treated within 24 hrs needed an additional dose. Duration of CMV and length of stay in the intensive care unit were significantly shorter in the treated group (4.6 +/- 0.8 and 6.4 +/- 0.9 days, respectively) compared with the control group (5.8 +/- 0.7 and 8.2 +/- 1.1 days, respectively) (p <.0001). No relevant complications were observed, and all the infants survived. CONCLUSIONS: Consistent with our previous study and others, this study shows that surfactant therapy improves gas exchange and respiratory mechanics and shortens CMV and intensive care unit stay in infants with severe RSV-induced respiratory failure.", "Infants with respiratory syncytial virus (RSV) bronchiolitis are deficient in surfactant, both in quantity and ability to reduce surface tension. New evidence suggests surfactant has a role in maintaining the patency of conducting airways, which has implications for RSV bronchiolitis. A randomized, controlled pilot study was undertaken to assess the effects of exogenous surfactant supplementation to RSV-positive infants on pulmonary mechanics, indices of gas exchange, and the phospholipid composition of bronchoalveolar lavage fluid (BALF). Nineteen ventilated infants (median corrected age 4 wk) received either two doses of surfactant (Survanta, 100 mg/kg) within 24 and 48 h of mechanical ventilation (n = 9), or air placebo (n = 10). Static lung compliance and resistance of infants in the placebo but not in the surfactant-treated group became progressively worse over the first 30 h following enrollment. Although no significant acute changes in gas exchange parameters were seen following surfactant, infants in the surfactant group showed a more rapid improvement in oxygenation and ventilation indices over the first 60 h of ventilation. Surfactant status was assessed from the concentration ratio in BALF of the disaturated phospholipid species dipalmitoylphosphatidylcholine to that of the monounsaturated species palmitoyloleoylphosphatidylcholine. This ratio correlated with both lung compliance (positively) and resistance (negatively), and over time increased in the treated group and declined in placebo infants. The data from this pilot study suggest that functional surfactant has a role in maintaining small airway patency as well as lung compliance in infants infected with RSV and an outcome study is now warranted.", "It is hypothesized that surfactant treatment helps to improve severe bronchiolitis by restoring surfactant system activity. This study aims to assess the effect of surfactant on gas exchange, peak inspiratory pressure and duration of mechanical ventilation and intensive care unit (ICU) stay in children with severe bronchiolitis.\n Twenty children with bronchiolitis requiring mechanical ventilation were randomly assigned to one of two groups (10 patients each). Group A was treated with continuous positive pressure ventilation (CPPV) plus surfactant. Group B was treated with CPPV only. Porcine-derived surfactant, 50 mg/kg body weight, was instilled into the trachea. Arterial tension of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, arterial tension of carbon dioxide (PaCO2), and peak inspiratory pressure (PIP) were assessed. Heart rate and non-invasive arterial blood pressure were monitored. The duration of CPPV and the length of ICU stay were also recorded. Finally, the incidence of complications and the survival rate were assessed.\n In group A, the PaO2/FiO2 ratio significantly improved from 1 h and a reduction in PaCO2 was noted from 12 h. A reduction of PIP was observed from 3 h. The duration of CPPV and the length of ICU stay were reduced in group A. No complications were reported in either group and all children survived.\n Surfactant treatment of severe bronchiolitis appeared to improve gas exchange, reduce PIP and shorten CPPV and ICU stay. However, these initial results must be confirmed by a larger and more rigorously controlled study." ]

[ "21051731", "19028741", "16085942" ]

[ "Internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole: a pragmatic randomized controlled trial.", "Value of internal limiting membrane peeling in surgery for idiopathic macular hole stage 2 and 3: a randomised clinical trial.", "Idiopathic macular hole surgery in Chinese patients: a randomised study to compare indocyanine green-assisted internal limiting membrane peeling with no internal limiting membrane peeling." ]

[ "To determine whether internal limiting membrane (ILM) peeling is effective and cost effective compared with no peeling in patients with idiopathic stage 2 or 3 full-thickness maculay hole (FTMH).\n This was a pragmatic multicenter randomized controlled trial. Eligible participants from nine centers were randomized to ILM peeling or no peeling (1:1 ratio) in addition to phacovitrectomy, including detachment and removal of the posterior hyaloid and gas tamponade. The primary outcome was distance visual acuity (VA) at 6 months after surgery. Secondary outcomes included hole closure, distance VA at other time points, near VA, contrast sensitivity, reading speed, reoperations, complications, resource use, and participant-reported health status, visual function, and costs.\n Of 141 participants randomized in nine centers, 127 (90%) completed the 6-month follow-up. Nonstatistically significant differences in distance visual acuity at 6 months were found between groups (mean difference, 4.8; 95% confidence interval [CI], -0.3 to 9.8; P = 0.063). There was a significantly higher rate of hole closure in the ILM-peel group (56 [84%] vs. 31 [48%]) at 1 month (odds ratio [OR], 6.23; 95% CI, 2.64-14.73; P < 0.001) with fewer reoperations (8 [12%] vs. 31 [48%]) performed by 6 months (OR, 0.14; 95% CI, 0.05-0.34; P < 0.001). Peeling the ILM is likely to be cost effective.\n There was no evidence of a difference in distance VA after the ILM peeling and no-ILM peeling techniques. An important benefit in favor of no ILM peeling was ruled out. Given the higher anatomic closure and lower reoperation rates in the ILM-peel group, ILM peeling seems to be the treatment of choice for idiopathic stage 2 to 3 FTMH. (Clinical Trials.gov number, NCT00286507.).", "To determine the effect of internal limiting membrane (ILM) peeling on anatomical and functional success rates in stage 2 and 3 idiopathic macular hole surgery (MHS).\n Randomised clinical trial of stage 2 and 3 idiopathic macular hole without visible epiretinal fibrosis and with less than 1 year's duration of symptoms. Eyes were randomised to (1) vitrectomy alone without retinal surface manipulation, (2) vitrectomy plus 0.05% isotonic Indocyanine Green (ICG)-assisted ILM peeling or (3) vitrectomy plus 0.15% Trypan Blue (TB)-assisted ILM peeling. Main outcomes were hole closure after 3 and 12 months and best-corrected visual acuity after 12 months.\n 78 eyes were enrolled. Primary closure rates were significantly higher with ILM peeling than without peeling for both stage 2 holes (ICG peeling 100%, non-peeling 55%, p = 0.014) and for stage 3 holes (ICG peeling 91%, TB peeling 89%, non-peeling 36%, p<0.001). Visual outcomes in eyes with primary hole closure were not significantly different between the groups.\n Dye-assisted ILM peeling was associated with significantly higher closure rates than non-peeling in both stage 2 and 3 MHS. Intraoperative ILM staining with 0.05% isotonic ICG was not associated with a significantly different visual outcome than non-peeling or TB peeling in eyes with primary hole closure. Trial registration number: NCT00302328.", "To compare the anatomical and visual outcomes of primary idiopathic macular hole surgery using indocyanine green-assisted internal limiting membrane peeling versus no internal limiting membrane peeling.\n Prospective randomised controlled clinical trial.\n University teaching hospital, Hong Kong.\n Fifty-one eyes of 49 Chinese patients with primary idiopathic macular hole were studied.\n Patients were randomised to undergo pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling (26 eyes) or surgery without internal limiting membrane peeling (25 eyes). Perfluorocarbon gas was used in all cases as internal tamponade.\n Primary macular hole closure rate and best-corrected visual acuity.\n The mean follow-up duration was 12 months (range, 6-23 months). Respectively to the indocyanine green-assisted internal limiting membrane peeling group and non-internal limiting membrane peeling group, the primary anatomical closure rate was 92.3% and 32.0% (P<0.001), whereas improvement in best-corrected visual acuity was 3.7 and 1.5 lines (P=0.002). More eyes in the first group (84.6%) had improvement of 2 or more lines of best-corrected visual acuity after surgery than in the second group (32.0%) [P<0.001]. Multivariate logistic regression showed indocyanine green-assisted internal limiting membrane peeling was the only significant predictor for primary closure of the macular hole (adjusted odds ratio=30.8).\n Indocyanine green-assisted internal limiting membrane peeling in idiopathic macular hole surgery results in significantly better anatomical and visual outcomes compared with non-internal limiting membrane peeling in Chinese patients." ]

[ "9390662", "11790236", "10891977", "17471547", "12529796", "15984021", "15804248", "10802796", "11113239", "12578937", "15159476", "14694498", "12707981", "20395096" ]

[ "A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies.", "Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study.", "Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial.", "Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six-month, double-blind, randomized, placebo-controlled trial.", "Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study.", "CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy.", "Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study.", "Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study.", "A placebo-controlled crossover trial of creatine in mitochondrial diseases.", "Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy.", "Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy.", "Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1.", "Beneficial effects of creatine supplementation in dystrophic patients.", "Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized, placebo-controlled 31P MRS study." ]

[ "Fatigue in patients with mitochondrial cytopathies is associated with decreased basal and postactivity muscle phosphocreatine (PCr). Creatine monohydrate supplementation has been shown to increase muscle PCr and high-intensity power output in healthy subjects. We studied the effects of creatine monohydrate administration (5 g PO b.i.d. x 14 days --> 2 g PO b.i.d. x 7 days) in 7 mitochondrial cytopathy patients using a randomized, crossover design. Measurements included: activities of daily living (visual analog scale); ischemic isometric handgrip strength (1 min); basal and postischemic exercise lactate; evoked and voluntary contraction strength of the dorsiflexors; nonischemic, isometric, dorsiflexion torque (NIDFT, 2 min); and aerobic cycle ergometry with pre- and post-lactate measurements. Creatine treatment resulted in significantly (P < 0.05) increased handgrip strength, NIDFT, and postexercise lactate, with no changes in the other measured variables. We concluded that creatine monohydrate increased the strength of high-intensity anaerobic and aerobic type activities in patients with mitochondrial cytopathies but had no apparent effects upon lower intensity aerobic activities.", "In a recent study, we showed that administration of low-dose creatine (Cr) (60 mg/kg daily) improved work capacity in patients with McArdle disease.\n To assess the efficacy of high-dose Cr therapy in McArdle disease.\n Randomized, double-blind, placebo-controlled crossover study.\n Nineteen patients with McArdle disease.\n Treatment with Cr, 150 mg/kg daily. Each treatment phase with Cr or placebo lasted 5 weeks.\n The patient's daily rating of symptoms of exercise intolerance. At the end of each treatment phase, serum creatine and serum creatine kinase levels, phosphorus 31 magnetic resonance spectroscopy, and surface electromyograms were assessed.\n Clinical end points revealed increases in the intensity of exercise-induced pain in working muscles (mean treatment-induced difference [d], 0.30 in log(score); 95% confidence interval [CI], 0.05-0.55; P =.02), the limitation of daily activities (d, 0.59; 95% CI, 0.22-0.97;P =.005), and body mass index (d, 0.33 kg/m2, 95% CI, 0.10-0.56 kg/m2; P =.008) with Cr use. Surface electromyograms revealed a smaller increase in the electromyographic amplitude over time during muscle contraction with Cr use (d, -13.52%/min; 95% CI, -23.71%/min to -3.34%/min; P =.01). There were no significant changes in phosphorus 31 magnetic resonance spectroscopy variables.\n Administration of high-dose Cr worsened the main clinical symptoms of exercise intolerance in McArdle disease. These neurologic adverse effects represent a major dose-limiting factor in Cr therapy for McArdle disease. Taken together with results of a previous study, the indication for symptomatic therapy with Cr needs to be clarified. An effective Cr dosage without adverse effects may be between 60 and 150 mg/kg daily.", "To determine whether treatment with creatine can improve exercise intolerance in myophosphorylase deficiency (McArdle disease).\n Double-blind, placebo-controlled crossover study with oral creatine monohydrate supplementation.\n Nine patients with biochemically and genetically proven McArdle disease were treated.\n Five days of daily high-dose creatine intake (150 mg/kg body weight) were followed by daily low-dose creatine intake (60 mg/kg). Each treatment phase with creatine or placebo lasted 5 weeks.\n The effect of treatment was estimated at the end of each treatment phase by recording clinical scores, ergometer exercise test results, phosphorus 31 nuclear magnetic resonance spectroscopy, and surface electromyography.\n Of 9 patients, 5 reported improvement of muscle complaints with creatine. Force-time integrals (P =.03) and depletion of phosphocreatine (P =.04) increased significantly during ischemic exercise with creatine. Phosphocreatine depletion also increased significantly during aerobic exercise (P =.006). The decrease of median frequency in surface electromyograms during contraction was significantly larger (P =.03) with creatine.\n This is the first controlled study indicating that creatine supplementation improves skeletal muscle function in McArdle disease.", "To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable.\n In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids.\n A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine.\n Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive.", "We assessed safety and efficacy of creatine monohydrate (Cr) in myotonic dystrophy (DM1) in a double-blind, cross-over trial. Thirty-four patients with defined DM1 were randomized to receive Cr and placebo for eight weeks (10.6 g day 1-10, 5.3 g day 11-56) in one of 2 treatment sequences. There was no significant improvement using manual and quantitative muscle strength, daily-life activities, and patients' own global assessment comparing verum with placebo administration. Cr supplementation was well tolerated without clinically relevant side effects, but did not result in significant improvement of muscle strength or daily-life activities.", "We tested the efficacy and safety of glutamine (0.6 gm/kg/day) and creatine (5 gm/day) in 50 ambulant boys with Duchenne muscular dystrophy in a 6-month, double-blind, placebo-controlled clinical trial. Drug efficacy was tested by measuring muscle strength manually (34 muscle groups) and quantitatively (10 muscle groups). Timed functional tests, functional parameters, and pulmonary function tests were secondary outcome measures. Although there was no statistically significant effect of either therapy based on manual and quantitative measurements of muscle strength, a disease-modifying effect of creatine in older Duchenne muscular dystrophy and creatine and glutamine in younger Duchenne muscular dystrophy cannot be excluded. Creatine and glutamine were well tolerated.", "The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.", "The authors assessed the safety and efficacy of creatine monohydrate (Cr) in various types of muscular dystrophies in a double-blind, crossover trial. Thirty-six patients (12 patients with facioscapulohumeral dystrophy, 10 patients with Becker dystrophy, 8 patients with Duchenne dystrophy, and 6 patients with sarcoglycan-deficient limb girdle muscular dystrophy) were randomized to receive Cr or placebo for 8 weeks. There was mild but significant improvement in muscle strength and daily-life activities by Medical Research Council scales and the Neuromuscular Symptom Score. Cr was well tolerated throughout the study period.", "To test the efficacy and safety of creatine (Cr) monohydrate in mitochondrial diseases, 16 patients with chronic progressive external ophthalmoplegia or mitochondrial myopathy were randomized in a crossover design to receive double-blind placebo or 20 g Cr/day for 4 weeks. Cr was well tolerated, but there were no significant effects with regard to exercise performance, eye movements, or activities of daily life. The power of this pilot study was limited and future multicenter trials are needed.", "The efficacy and safety of creatine monohydrate (Cr) in patients with myotonic dystrophy type 2/proximal myotonic myopathy were studied in a small placebo-controlled double-blind trial. Twenty patients received either Cr or placebo for 3 months. After 3 months, there were no significant differences of muscle strength as assessed by hand-held dynamometry, testing of maximum grip strength, Medical Research Council scoring, and the Neuromuscular Symptom Score between the two groups. Some measures indicated trends toward mild improvement with Cr. Myalgia improved in two patients.", "To determine whether creatine monohydrate (CrM) supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD).\n Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and gamma-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N-telopeptides).\n During the CrM treatment phase, there was an increase in handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a loss of global muscle strength (p = 0.056) only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p < 0.05), and CrM treatment was associated with a reduction in N-telopeptides (p < 0.05).\n Four months of CrM supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.", "Creatine monohydrate (CrM) supplementation may increase strength in some types of muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1) did not find a significant treatment effect, but measurements of muscle phosphocreatine (PCr) were not performed. We completed a randomized, double-blind, cross-over trial using 34 genetically confirmed adult DM1 patients without significant cognitive impairment. Participants received CrM (5 g, approximately 0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out. Spirometry, manual muscle testing, quantitative isometric strength testing of handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion endurance, functional tasks, activity of daily living scales, body composition (total, bone, and fat-free mass), serum creatine kinase activity, serum creatinine concentration and clearance, and liver function tests were completed before and after each intervention, and muscle PCr/beta-adenosine triphosphate (ATP) ratios of the forearm flexor muscles were completed at the end of each phase. CrM supplementation did not increase any of the outcome measurements except for plasma creatinine concentration (but not creatinine clearance). Thus, CrM supplementation at 5 g daily does not have any effects on muscle strength, body composition, or activities of daily living in patients with DM1, perhaps because of a failure of the supplementation to increase muscle PCr/beta-ATP content.", "The effect of creatine (Cr) supplementation on muscle function and body composition of 12 boys with Duchenne muscular dystrophy and three with Becker dystrophy was evaluated by a randomized double-blind cross-over study (3 g Cr or maltodextrin daily for 3 months, with wash-out period of 2 months). After placebo, no change was observed in maximal voluntary contraction (MVC) and resistance to fatigue, whereas total joint stiffness (TJS) was increased by approximately 25% (P < 0.05). The patients receiving Cr did not show any change in TJS, improved MVC by 15% (P = 0.02), and almost doubled their resistance to fatigue (P < 0.001). In patients still independent of a wheelchair (n = 5), bone mineral density increased by 3% (P < 0.05), and urinary excretion of collagen type I cross-linking N-telopeptide declined to about one third (P < 0.001) after Cr. No adverse effect was observed. Thus, Cr may provide some symptomatic benefit in these patients.", "Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy ((31)P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9-5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5-4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.\n Copyright 2010 Elsevier Inc. All rights reserved." ]

[ "10830460" ]

[ "Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome." ]

[ "Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO2) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO2 when entering the study. There were no significant differences between the groups in a/A PO2 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice." ]

[ "7849868", "7792546" ]

[ "Controlled two year follow up of rehabilitation for disorders in the neck and shoulders.", "The role of the psychologist in multidisciplinary treatments for chronic neck and shoulder pain: a controlled cost-effectiveness study." ]

[ "To evaluate the effects of an early, active, and multidisciplinary rehabilitation programme for neck and shoulder disorders.\n Primary health care and industrial health care of a nonrandomised, controlled, cohort was followed up over two years in a geographically defined area. The cohort consisted of working people who consulted a physician about disorders of the neck or shoulders from 1 August 1988 to 31 October 1989. Criteria for acceptance; not chronic symptoms, patients had sick leave of no more than four weeks. Disorders were not caused by trauma, infections, malignancy, rheumatic diseases, abuse, or pregnancy. 107 people qualified for the study, 87% were followed up for two years. They were divided into two groups. One group obtained active, multidisciplinary rehabilitation for eight weeks that comprised physical training, information, education, social interaction, and work place visits. Controls were given traditional treatment; physiotherapy, medication, rest, and sick leave. The main outcome measures were: average number of days of sick leave for the two years after rehabilitation, subjective pain on a visual analogue scale, and ratings on seven subscales of the sickness impact profile.\n At 12 and 24 months of follow up effects of the active rehabilitation programme did not differ from traditional treatment in any of the outcome measures. New work task (P < 0.05) or changed work place (P < 0.001) during the follow up period were associated with decreased sick leave, independent of treatment.\n Active, multidisciplinary rehabilitation of neck and shoulder disorders was not more effective than traditional treatment. Changed work conditions were associated with decreased sick leave, independent of type of treatment provided.", "This study was designed to determine a cost-effective use of psychologist resources in multimodal cognitive-behavioural treatments (MMCBT) for chronic neck/shoulder pain. A randomised controlled trial was conducted with 66 patients divided in two groups. The first group (A) was treated following the approach of MMCBT with the clinical psychologist only functioning as a \"coach\" to the other health professionals. In this group, the psychologist had on average 5 hours of input per patients. The second group (B) was treated with the same inpatient MMCBT but with the behavioural component administered by the clinical psychologist directly to the patients. In this second group the psychologist had on average 17 hours of input per patient in the entire intervention. The outcome variables included physical, emotional and social factors, and sick-leave. Both groups showed significant improvements over time. The improvements were evident only in sub-groups, specifically in women. The only significant difference between the groups was in \"perceived helplessness\" favouring the \"psychologist contact\" setting. It is concluded that in terms of input of clinical psychology, the treatment setting with the \"coaching\" technique proved to be the most cost-effective use of the psychologist in the two treatment settings investigated." ]

[ "400290", "2184787", "828099", "1971493", "1560482", "1296947", "11791989", "11939303", "1940217", "5301383", "5308697", "3517181", "9713544", "9692167", "9481098" ]

[ "[Follow-up survey on the long-term effects of DEC medicated salt in the control of filariasis bancrofti (author's transl)].", "Eradication of bancroftian filariasis by diethylcarbamazine-medicated common salt on Little Kinmen (Liehyu district), Kinmen (Quemoy) Islands, Republic of China.", "Field trial on control of bancroftian filariasis using common salt medicated with diethylcarbamazine.", "Filariasis eradication on Kinmen Proper, Kinmen (Quemoy) Islands, Republic of China.", "Mass treatment of filariasis using DEC-medicated salt.", "Efficacy of diethylcarbamazine medicated salt in interrupting Brugia malayi transmission in hill tribe settlements in Kerala State.", "A community-based trial for the control of lymphatic filariasis and iodine deficiency using salt fortified with diethylcarbamazine and iodine.", "Efficacy of mass single-dose diethylcarbamazine and DEC-fortified salt against bancroftian filariasis in Papua New Guinea six months after treatment.", "Long term effect of diethylcarbamazine medicated common salt on bancroftian filariasis.", "Control of Bancroftian filariasis by cooking salt medicated with diethylcarbamazine.", "The effect of salt medicated with diethylcarbamazine in bancroftian filariasis.", "Control of bancroftian filariasis by salt medicated with diethylcarbamazine citrate.", "The efficacy, tolerability and safety of diethylcarbamazine-fortified salt in the treatment of the microfilaraemias of brugian filariasis: an open, hospital-based study.", "Long-term effect of mass diethylcarbamazine chemotherapy on bancroftian filariasis, results at four years after start of treatment.", "Efficacy of diethylcarbamazine-medicated salt for microfilaraemia of Brugia malayi." ]

[ "nan", "Since bancroftian filariasis constituted a major public health problem on Little Kinmen (Liehyu District), Kinmen (Quemoy) Islands, a control programme was conducted on this island from 1970 to 1982. A pre-control survey recorded a microfilarial rate (mfr) of 9.6%, a night blood microfilarial density (mfd) of 14.4/20 microliters blood, and a clinical rate of 26.2%. Culex quinquefasciatus was found to be the only vector of the parasitosis on the island, with an infection rate (Ir) with all filarial larval stages of 9.1% and a larval density (Ld) of 6.2. Diethylcarbamazine (DEC)-medicated salt (0.33% w/w) was administered to the whole population on Little Kinmen. Each person was estimated to take 12.7 g salt with 42 mg DEC daily for six months (July-December 1974). All accepted the programme, and no adverse side-effect was noted. During the control, the mfr and mfd were reduced to 0.3% and 1.9/20 microliters blood. The Ir and Ld were reduced to 0.8% and 1.3. Eight post-control surveys (1975-1982) revealed only two of 459 pre-control carriers positive and the remaining population of 7125 inhabitants negative. The two carriers were cured with a course of 5 g DEC. All family members of these carriers and their neighbours' families were given DEC-medicated salt for four months to clear the only remaining source of filarial transmission. In addition to a reduction in the prevalence of filariasis in humans and in mosquitoes to zero, the clinical manifestations disappeared in 52.4% of the pre-control carriers and improved in 19.0%. There was no change in 19.8 and 8.7% had new manifestations.", "nan", "A control program for bancroftian filariasis was conducted on Kinmen Proper from 1970 to 1982. The combined method of mass chemotherapy with diethylcarbamazine (DEC) for microfilarial carriers and larvicide with sumithion for mosquitoes was used on the island for 3 years (1974-76). The microfilarial rate and microfilarial density decreased from 8.4% and 14.6/20 microns in 1970-73 to 0.7% and 5.3/20 microns in 1976. The infection rate, infective rate, and larval density of Culex quinquefasciatus, the only mosquito vector of the parasite, decreased from 10.3%, 6.4%, and 6.4 in 1970-73 to 0.3%, 0.2%, and 1.3, in 1976, respectively. For final elimination of the infection, DEC medicated salt (0.33%, w/w) was then administered to the whole population for 6 months (March-September 1977). All accepted the program and no adverse side-effects were noted. Six annual follow-up surveys (1977-82) revealed only 3 out of 3853 previous carriers to be positive. These carriers were cured with a course of 5 g DEC. All family members of the 3 carriers and of the 12 neighbouring families were also given DEC medicated salt for 4 months in order to clear the only remaining source of filarial transmission. In conclusion, administration of DEC medicated salt is simple, rapid, safe, inexpensive, efficient, and practical for filariasis control or eradication.", "Diethylcarbamazine (DEC)-medicated salt was used to control bancroftian filariasis in 20 endemic counties and cities of Fujian Province in China. The population was 5,189,126 and the microfilaria (mf) rates were between 1.56 and 11.81%. The total dose of DEC was 6-10.5 g per person over a period of 2-4 months. Six to 9 months after treatment the mf rate was reduced to 0-0.57% with a mean of 0.07% (621/823,796). In 184 villages sampled one year post treatment the mf rate was 0.22% (371/171,067) and in 29 villages 2-4 years after treatment the mf rate was 0.05% (31/56,459). In a region of endemic Malayan filariasis, with a population of 67,778 and mf rate of 3.82-4.36%, treatment with DEC-medicated salt to a dosage of 3.2 g DEC per person was administered for 2 months. Six months after treatment the mean mf rate was reduced from 4.08 to 0.26% (10/3841). Filariasis in all the villages controlled with DEC-medicated salt reached the basic criteria of elimination (mf rate below 1%).", "A filariasis survey carried out about eight years after achieving zero microfilaria (mf) rates following administration of diethylcarbamazine (DEC) medicated salt in the Kani hill tribe settlements in Quilon and Thiruvananthapuram districts of Kerala State revealed that there was no reappearance of Brugia malayi infection in the experimental areas. Mf rates were maintained at zero level in the experimental villages, while in the control villages, 2.9 per cent mf positives were observed. Mansonia (Mansonioides) uniformis dissected did not reveal filarial infection. It is concluded that DEC medicated salt regime in the experimental areas of Kani hill tribe settlements has been successful in effectively interrupting B. malayi transmission. Pilot studies in other B. malayi endemic areas of India using DEC medicated salt regime with the objective of eliminating B. malayi transmission are advocated, since the parasite has a restricted distribution in India and is already showing a declining trend.", "To evaluate the effectiveness of salt fortified with diethylcarbamazine (DEC) and iodine for elimination of Bancroftian filariasis and iodine deficiency, all consenting residents of Miton, Haiti (n = 1,932) were given salt fortified with 0.25% diethylcarbamazine and 25 ppm of iodine for one year. Wuchereria bancrofti microfilaria prevalence and intensity, antigenemia, and urinary iodine were measured before and one year after salt distribution began. To measure the effect of DEC-fortified salt on adult worm motility, 15 microfilaria-positive men were examined by ultrasound of the scrotal area. Entomologic surveys were conducted to determine the proportion of W. bancrofti-infected Culex quinquefasciatus. After one year of treatment, the prevalence and intensity of microfilaremia were both reduced by more than 95%, while antigenemia levels were reduced by 60%. The motility of adult worms, as detected by ultrasound, was decreased, but not significantly, by DEC-fortified salt. The proportion of vector mosquitoes carrying infective stage larvae decreased significantly from 2.3% in the nine months before the intervention to 0.2% in the last three-month follow-up period. Iodine deficiency, which had been moderate to severe, was eliminated after one year of iodized salt consumption. The DEC-fortified salt was well accepted by the community and reduced microfilaremia and transmission to low levels in the absence of reported side effects. Based on these results, salt cofortified with DEC and iodine should be considered as a concurrent intervention for lymphatic filariasis and iodine deficiency elimination programs.", "The efficacy of two diethylcarbamazine (DEC) treatment strategies to control bancroftian filariasis, diethylcarbamazine-fortified salt (DEC-FS) and a single DEC dose on mass administration, was evaluated in two communities in Papua New Guinea with pretreatment antigen prevalence of 55% and 71%. In the first community 0.2% w/w diethylcarbamazine-fortified salt was distributed monthly to accepting households at no cost for 12 months. In the second community a single DEC dose based on body size but designed to give about 6 mg/kg was administered to eligible acceptors. Despite wide variation in antigen prevalence among study villages there were marked reductions in prevalences under both treatment strategies. Among individuals antigenaemic on day 0, DEC-FS and a single DEC dose gave filaria antigen clearance rates of 43% and 13%, respectively. In the salt-treated community the incidence of antigenaemia after 6 months in acceptors from households that received 5 kg or more of DEC-FS was 14% whereas in those receiving less than 5 kg salt was 4%. The incidence rates in the second community in those that received < 2.5 and > or = 2.5 tablets were 16% and 8%, respectively. The two treatment strategies were simple to manage and appropriate for developing countries and were widely accepted. DEC-FS was more efficacious than single-dose DEC tablets but a single administration of DEC tablets is easier to administer.", "nan", "In small-scale pilot trials, filarial infection can usually be reduced to low levels by oral administration of diethylcarbamazine to all the persons concerned; but in mass campaigns it is often difficult to persuade large numbers of people to swallow the tablets. In order to overcome this difficulty the authors propose that the compound be incorporated into cooking salt, as has been done with chloroquine to control malaria. There are many reasons why this method of medication should be more effective against filariasis than it has often been against malaria.Laboratory trials showed that cooking the compound in food did not make it toxic for rats or diminish its antifilarial activity. A pilot trial was carried out at Recife, Brazil, in which 1000 adults received salt containing 0.4% diethylcarbamazine (corresponding to a daily intake of 100 mg/day) for 40 days, and then salt containing 0.1% compound for a year. This medication was simple to administer; it was quite acceptable to the subjects; it caused no untoward effects; and it removed almost all the microfilariae from the blood. Administration of medicated salt (0.3%) for 18 days to another group of 1300 adults was well tolerated and produced a considerable reduction of the microfilarial load; but this short period was insufficient to remove all the microfilariae.The authors recommend that this method of administering diethylcarbamazine to large numbers of people should be investigated further to see if it could be used for mass campaigns to control filariasis.", "The paper describes a trial conducted in Tanzania of the effect on bancroftian microfilaraemia of common salt medicated with diethylcarbamazine at a 0.1% (w/w) concentration, when given to a closed population of 600-700 with a known salt intake.After good observer agreement in microfilarial counting had been demonstrated, quantitative blood surveys were performed monthly on known carriers. Paired pretreatment microfilarial counts from the same patients at an interval of 4 months suggested a natural fluctuation in microfilarial densities and emphasized the need for parallel concurrent controls during treatment.During the trial the mean microfilarial densities fell steadily, being reduced by 73% at 3 months and 90% after 6 months. Tolerance to the drug-salt mixture was extremely good.Problems of planning, salt preparation and assessment of results are discussed and the importance of correct experimental design in future trials is stressed. The authors suggest that a trial of salt containing 0.2% (w/w) diethylcarbamazine may achieve optimum results. They point out that, while the use of diethylcarbamazine-medicated salt may prove useful in reducing transmission in closed communities or in endemic areas with no alternative source of salt, its extension to national populations as a sole means of bancroftian filariasis control would be of problematical value.", "nan", "Cooking salt fortified with diethylcarbamazine (DEC) has been successfully used to control lymphatic filariasis in several parts of the world. The kinetics and efficacy of DEC-fortified salt in clearing microfilaraemias of Brugia malayi and the salt's tolerability and safety are examined in this study. Twenty individuals with B. malayi microfilaraemias (pre-treatment levels of 108-6358 microfilariae/ml; median = 309/ml) consumed DEC-fortified salt (0.2%, w/w) with their food for 1 year, initially in hospital (for 1 week) and later at home. The mean daily intake of DEC was 21.4 mg (range = 9.0-39.4 mg). Even on the first day of consuming the salt, there was a decrease in the microfilarial levels of 14 patients and a sharp increase in six patients. Microfilarial levels tended to fluctuate thereafter but there was a progressive, general decline. At the end of the study year, eight patients were amicrofilaraemic and microfilarial clearance was > 95% in 58% of the patients. Eight patients did not develop any adverse reactions. Lymph-node tenderness and enlargement were seen in eight patients (40%), and dilated, inflamed lymphatic channels standing out as cords ('string sign') were seen in another five patients. These reactions were transient and did not require any specific treatment. The DEC-fortified salt was well accepted by the study population. The DEC content of fortified salt and the duration of its use for the control of brugian filariasis need to be re-examined. Health education should include messages that mild, self-limiting, adverse reactions are likely to occur even with the use of such salt.", "The long-term effect of 4 strategies for control of bancroftian filariasis using mass diethylcarbamazine (DEC) chemotherapy was assessed and compared in 4 endemic communities in Tanzania over a period of 4 years. The strategies were the standard 12 d treatment (strategy I), semi-annual single dose treatment (strategy II), monthly low dose treatment (strategy III), and DEC-medicated salt treatment (strategy IV). Treatment was given only during the first year. All strategies resulted in considerable reductions in microfilaraemia, with maximum effects occurring 1-2 years after start of treatment. At 2 years, the greatest reductions were seen for strategies III and IV, followed by strategy II and finally strategy I. The overall performance of the 4 strategies evaluated over the 4 years period followed the same sequence. Between the 2 years and 4 years follow-up surveys, a significant increase in microfilarial (mf) burden occurred in all 4 communities, but the mf geometric mean intensities (GMI) remained low. Thus, in individuals who were microfilaraemic before treatment, the rates of microfilaraemia were 66%, 44%, 34% and 43%, and the mf GMIs were 6.8%, 3.3%, 0.5% and 0.7%, of pre-treatment level, 4 years after start of treatment with strategies I, II, III and IV, respectively. Most individuals who developed microfilaraemia between the 2 years and 4 years follow-up surveys had been microfilaraemic before the start of treatment. Hence, the rate of development of microfilaraemia was much higher (18 times on average in the 4 communities) among those who were microfilaraemic before treatment than among those who were amicrofilaraemic. The long-lasting effect of treatment adds a promising potential to the use of mass DEC chemotherapy for the control of bancroftian filariasis.", "Pilot studies in India and abroad have demonstrated the benefit of cooking salt fortified with diethylcarbamazine citrate (DEC) for the control of lymphatic filariasis. In India, DEC-medicated salt has been introduced on a commercial basis in the Cherthala region of Kerala, which is endemic for Brugia malayi (B. malayi). We studied the efficacy of DEC-medicated salt in the clearance of microfilaraemia of B. malayi.\n Eighteen cases of microfilaraemia (11 men; 7 women) were selected; 14 in the experimental group (i.e. treated with 0.2% w/w DEC-medicated salt) and the rest as the control group who were given a placebo. The consumption of salt and the status of parasitaemia were monitored till all the microfilaria carriers became negative.\n There was a significant reduction in the density of microfilariae (intensity) among the treated individuals over a period of time. The duration required for the clearance of microfilariae ranged from 9 to 30 [mean (SD) 19.4 (1.7)] weeks. All microfilaraemics except one reported side-effects which were mild-to-moderate and persisted for a maximum period of one month.\n DEC-medicated salt effectively clears microfilariae within 30 weeks in parasitaemic individuals. No 'endemic normals' reported any side-effects, though these were common among the microfilaria carriers." ]

[ "15082480", "15228184", "14719195", "15146409" ]

[ "Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.", "Rapid alleviation of signs and symptoms of rheumatoid arthritis with intravenous or subcutaneous administration of adalimumab in combination with methotrexate.", "Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis).", "Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial." ]

[ "To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed.\n In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was > or =20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI).\n After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p< or =0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p< or =0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p< or =0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p< or =0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (-0.29, -0.39, -0.38, -0.49 v -0.07; p< or =0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p< or =0.05).\n Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.", "This randomized, placebo-controlled, double-blind, Phase 1 study assessed the magnitude, onset, and duration of response with intravenous (i.v.) and subcutaneous (s.c.) adalimumab (Humira, Abbott Laboratories) combined with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite previous MTX therapy.\n Fifty-four patients were randomized to two injections of i.v. or s.c. adalimumab (1 mg/kg) or placebo while continuing on MTX (mean dose, 15.7 mg/week). Dosing intervals were determined by the European League Against Rheumatism (EULAR) response criteria, and were allowed to range from 1 to 3 months. Efficacy was mainly assessed using the EULAR response criteria and the American College of Rheumatology (ACR) response criteria.\n Moderate EULAR response was achieved at least once within 29 days after the first injection in 83% and 61% of patients receiving i.v. and s.c. adalimumab respectively, compared with 44% for placebo [probability (p) < or = 0.05 for i.v. adalimumab versus placebo]. A 20% improvement in disease activity according to the ACR criteria (ACR20 response) was achieved by 72% and 67% of patients receiving i.v. and s.c. adalimumab respectively, compared with 28% for placebo (p < or = 0.01 and p < or = 0.05, respectively, versus placebo). By Day 15 after the first and second injections, statistically significant moderate EULAR and ACR20 response rates were achieved with either i.v. or s.c. adalimumab compared with placebo (p < or = 0.05). The mean times to second injection for i.v. adalimumab, s.c. adalimumab, and placebo were 42.2 days (range: 27-84 days), 38.3 days (range: 26-85 days), and 28.4 days (range: 26-32 days), respectively (minimum time allowed by the protocol between the first and second injections was 4 weeks). Adalimumab in combination with MTX was well tolerated, with no patients being withdrawn because of adverse events.\n Either i.v. or s.c. adalimumab added to MTX significantly improved the signs and symptoms of RA compared with MTX alone. Subcutaneously administered adalimumab appeared to provide a response that was as great, as rapid, and as enduring as that with i.v. adalimumab.", "This study, known as STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis), evaluated the safety and efficacy of adalimumab (Humira), a fully human monoclonal tumor necrosis factor-alpha (TNF-a) antibody, when given with standard antirheumatic therapy in patients with active rheumatoid arthritis (RA) not adequately responding to such therapies. Standard antirheumatic therapy included traditional disease modifying antirheumatic drugs (DMARD), low dose corticosteroids, nonsteroidal antiinflammatory drugs (NSAID), and/or analgesics.\n In this 24-week, double-blind, placebo-controlled study, 636 patients with RA were randomly assigned to receive adalimumab 40 mg subcutaneously (sc) every other week (n = 318) or placebo (n = 318) while continuing standard antirheumatic therapy. The frequencies of adverse events, serious adverse events, severe or life-threatening adverse events, adverse events leading to withdrawal, infection, or serious infection were the primary endpoints. Secondary endpoints were determined by American College of Rheumatology (ACR) response criteria.\n During the study, the majority of patients received concomitant traditional DMARD (83.5%) and/or corticosteroids, NSAID, and/or analgesics (97.3%). Overall, 56.0% of patients continued treatment with one, 23.6% with 2, and 3.9% with > or = 3 traditional DMARD. At 24 weeks, there were no statistically significant differences between the adalimumab and placebo groups in their respective rates of adverse events (86.5% vs 82.7%), serious adverse events (5.3% vs 6.9%), severe or life-threatening adverse events (11.9% vs 15.4%), or those leading to withdrawal (2.8% vs 2.2%). There were also no statistically significant differences in the rates of infections (52.2% vs 49.4%) or serious infections (1.3% vs 1.9%) between the groups. The incidence and types of adverse events did not vary between adalimumab- and placebo-treated patients by the number of concomitant traditional DMARD (0, 1, or 2). Adalimumab-treated patients compared with placebo-treated patients achieved statistically superior ACR20 (52.8% vs 34.9%), ACR50 (28.9% vs 11.3%), and ACR70 (14.8% vs 3.5%) response rates at Week 24 (p < or = 0.001).\n This study demonstrated that addition of adalimumab 40 mg given sc every other week to concomitant standard antirheumatic therapy is well tolerated and provides significant improvements in signs and symptoms of RA. The data indicate that adalimumab is a safe and effective therapeutic option in patients with active RA who have an inadequate response to standard antirheumatic therapy, including one or more traditional DMARD, corticosteroids, NSAID, and analgesics.", "Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX).\n In this multicenter, 52-week, double-blind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX. The primary efficacy end points were radiographic progression at week 52 (total Sharp score by a modified method [TSS]), clinical response at week 24 (improvements of at least 20% in the American College of Rheumatology core criteria [ACR20]), and physical function at week 52 (disability index of the Health Assessment Questionnaire [HAQ]).\n At week 52, there was statistically significantly less radiographic progression, as measured by the change in TSS, in the patients receiving adalimumab either 40 mg every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P < or = 0.001 for each comparison). In addition, there were statistically significant changes in the components of the TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus 30% of patients in the placebo group (P < or = 0.001 for each comparison). At week 52, ACR20 responses were achieved by 59% and 55% of patients taking adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of patients taking placebo (P < or = 0.001 for each comparison). At week 52, physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P < or = 0.001 for each comparison). A total of 467 patients (75.4%) completed 52 weeks of treatment. Adalimumab was generally well tolerated. Discontinuations occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated patients. The rate of adverse events (both serious and nonserious) was comparable in the adalimumab and placebo groups, although the proportion of patients reporting serious infections was higher in patients receiving adalimumab (3.8%) than in those receiving placebo (0.5%) (P < or = 0.02), and was highest in the patients receiving 40 mg every other week.\n In this 52-week trial, adalimumab was more effective than placebo at inhibiting the progression of structural joint damage, reducing the signs and symptoms, and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX." ]

[ "9636863", "9203426", "18505387", "15172774" ]

[ "Combination therapy with fluconazole and flucytosine for cryptococcal meningitis in Ugandan patients with AIDS.", "Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.", "High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial.", "Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial." ]

[ "We performed a randomized trial in which combination therapy with fluconazole and short-term flucytosine was compared with fluconazole monotherapy in 58 patients with AIDS-associated cryptococcal meningitis (CM). Thirty of these patients were randomized to receive combination therapy with fluconazole, 200 mg once a day for 2 months, and flucytosine, 150 mg/(kg.d) for the first 2 weeks, and 28 were randomized to receive monotherapy with fluconazole at the same dose for 2 months. Patients in both groups who survived for 2 months received fluconazole as maintenance therapy at a dose of 200 mg three times per week for 4 months. The combination therapy prevented death within 2 weeks and significantly increased the survival rate among these patients (32%) at 6 months over that among patients receiving monotherapy (12%) (P = .022). The combination therapy also resulted in a significant decrease in the severity of headache after 1 month of treatment, compared with monotherapy (P = .005). No serious adverse reactions were observed in patients receiving either regimen. These data indicate that treatment with fluconazole and short-term flucytosine is a cost-effective and safe regimen that improves the quality of life for patients with AIDS-associated CM in developing countries where human immunodeficiency virus is endemic.", "Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization.\n In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks.\n At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P=0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization.\n For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.", "The standard therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis of amphotericin B (AmB; 0.7 mg/kg per day) plus flucytosine frequently takes >2 weeks to sterilize the cerebral spinal fluid, and acute mortality remains high. A dosage range for AmB of 0.7-1 mg/kg per day is noted in current guidelines, but there are no data comparing 0.7 mg/kg per day with 1 mg/kg per day.\n Sixty-four HIV-seropositive, antiretroviral therapy-naive patients in Cape Town, South Africa, who experienced their first episode of cryptococcal meningitis during the period May 2005-June 2006 were randomized to receive either (1) AmB, 0.7 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 1; 30 patients); or (2) AmB, 1 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 2; 34 patients). Regimens were given for 2 weeks, followed by treatment with oral fluconazole. The primary outcome measure was early fungicidal activity, as determined by results of serial, quantitative cerebral spinal fluid cryptococcal cultures. Secondary outcome measures were safety and mortality. The median duration of follow-up was 1 year.\n Early fungicidal activity was significantly greater for group 2 than for group 1 (mean +/- SD, -0.56 +/- 0.24 vs. -0.45 +/- 0.16 log cfu/mL of cerebral spinal fluid per day; P = .02). The incidence of renal impairment did not significantly differ between the 2 groups. Anemia was associated with female sex and, less strongly, with membership in group 2. Renal impairment and anemia reversed after the regimen was switched to fluconazole. Two- and 10-week mortality rates were 6% and 24%, respectively, with no difference between groups.\n AmB, 1 mg/kg per day, plus flucytosine is more rapidly fungicidal than is standard-dose AmB plus flucytosine. Because of its size, this study provides limited data on any difference in toxicity between the regimens, but toxicities were manageable and reversible.\n ISRCTN68133435 (http://www.controlled-trials.com).", "It frequently takes more than 2 weeks for drug treatments for cryptococcal meningitis to sterilise cerebrospinal fluid (CSF). In-vitro and animal studies lend support to the use of combinations of amphotericin B, flucytosine, and fluconazole for treatment of cryptococcosis. We compared the fungicidal activity of combinations of these drugs for initial treatment of patients with cryptococcal meningitis.\n 64 patients with a first episode of HIV-associated cryptococcal meningitis were randomised to initial treatment with: amphotericin B (0.7 mg/kg daily); amphotericin B plus flucytosine (100 mg/kg daily); amphotericin B plus fluconazole (400 mg daily); or triple therapy with amphotericin B, flucytosine, and fluconazole. Our primary endpoint was fungicidal activity, measured by the rate of reduction in CSF cryptococcal colony-forming units (CFU) from serial quantitative CSF cultures on days 3, 7, and 14 of treatment.\n Baseline CSF CFU counts were an important prognostic factor. Clearance of cryptococci from the CSF was exponential and was significantly faster with amphotericin B plus flucytosine than with amphotericin B alone (p=0.0006), amphotericin B plus fluconazole ( p=0.02), or triple therapy (p=0.02).\n At these doses, amphotericin B plus flucytosine is the most rapidly fungicidal regimen. Quantification of CSF cultures provides a powerful new means to accurately assess the fungicidal activity of new treatment regimens for cryptococcal meningitis." ]

[ "15164191", "8723378", "9295178", "10617168", "8560135", "3057399", "3545461", "17274039" ]

[ "Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic acid compared with slow-release levodopa/benserazid.", "L-DOPA/carbidopa for nocturnal movement disorders in uremia.", "Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa.", "Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial.", "L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial.", "Treatment of restless legs syndrome and periodic movements during sleep with L-dopa: a double-blind, controlled study.", "Restless legs syndrome treatment with dopaminergic drugs.", "Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial." ]

[ "We aimed to compare the efficacy of valproic acid (VPA) on paresthesias and sleep in RLS to that of levodopa (LD). Twenty patients with idiopathic restless legs syndrome (RLS) were treated with 600 mg slow-release VPA and 200 mg slow-release LD+50mg benserazid in a randomized, placebo-controlled, cross-over, double-blind setting with polysomography (PSG) at the end of each 3-week treatment periods. There was no major difference between the efficacy of valproic acid or LD. Periodic leg movements in sleep (PLMS) and PLM arousal index (PLMAI) significantly decreased with LD (p < or= 0.005). However, LD, but not VPA, significantly increased arousals not associated with PLMS (p = 0.002). Decrease of intensity and duration of RLS symptoms were more pronounced with VPA (p < or= 0.022) than with LD (NS). We conclude that slow-release VPA provides a treatment alternative for RLS.", "Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) are sleep disorders that are common and distressing to uremic patients. There are few data regarding effective treatment in this population. Five chronic hemodialysis patients completed a double-blind, placebo-controlled, crossover study using a single bedtime dose of controlled release L-DOPA/carbidopa (100/25 mg) for treatment of RLS and sleep disruption. Leg movements per hour of sleep and percentage of sleep time accompanied by leg movements were decreased with treatment (101.0 +/- 29.1 events/hour on placebo vs. 61.0 +/- 28.3 events per hour on drug, p = 0.006; and 15.1 +/- 4.9% of sleep time with leg movements on placebo vs. 8.6 +/- 4.0% on drug, p = 0.014). In addition, arousals associated with leg movements (mean 209 +/- 49 events on placebo, mean 108 +/- 46 events on drug) and the leg movement arousal index (mean 59 +/- 23 events/hour on placebo, mean 23 +/- 9 events/hour on drug) were decreased by active medication (p = 0.03 and 0.04, respectively). Patients, however, continued to have very disrupted sleep and we could not document consistent subjective or objective improvement in overall sleep except for an increase in slow-wave sleep (SWS) from 9.0% to 22.8% (p = 0.01). The patterns of movements during sleep were not uniform in different patients, and the movements, although often periodic, were much longer than defined for PLMS. Because of this, finding suitable objective parameters to analyze was problematic. Measuring the percentage of sleep time during which there were leg movements was probably the most efficient and reproducible means of quantitating this disorder. Thus, although controlled-release L-DOPA/carbidopa at a dose of 100/25 mg given once nightly reduced leg movements and increased SWS, sleep continued to be disrupted. Whether higher doses or more frequent dosing is effective requires further investigation.", "A double-blind randomized crossover study of 0.125 mg Pergolide (Lilly) at bedtime versus 250mg L-Dopa + Carbidopa (Roche) was conducted in 16-day phases in 11 patients with idiopathic restless legs syndrome. Two patients reported a partial and 9 patients a complete relieve of motor restlessness while receiving Pergolide. Only 1 patient experienced an improvement of restlessness after L-Dopa. The patients showed polysomnographically a mean decrease in NMS cluster disturbed time by 45% from control on L-Dopa (p < 0.025) and by 79% from control on Pergolide (p < 0.001). In addition, Pergolide increased the total sleep time compared to L-Dopa (p < 0.05). In conclusion, the dopamine agonist Pergolide is superior to L-Dopa in the treatment of RLS and NMS.", "To investigate the efficacy and safety of levodopa plus benserazide in the treatment of restless legs syndrome (RLS), in terms of the frequency of periodic limb movements (PLMs), objective and subjective criteria of sleep, onset of action, and withdrawal effects.\n A randomized, double-blind, placebo-controlled, multicenter, crossover trial, with two 4-week treatment periods.\n Outpatient units of three specialist centers in Germany.\n Eligible patients had to fulfill the diagnostic criteria of the International RLS Study Group and have sleep disturbances and PLMs during sleep shown on polysomnography at screening. Thirty-five patients were recruited, of whom 32 (13 men, 19 women) completed the study.\n Patients received a single dose of standard-release levodopa/benserazide 100/25 mg or placebo at bedtime each night for 4 weeks, before crossing over to receive the alternative treatment for a further 4 weeks; the dose could be doubled if required. The average dosages were 159 +/- 31 mg of levodopa and 1.56 +/- 0.29 capsules of placebo.\n Levodopa/benserazide significantly reduced the number of PLMs per hour (p<0.0001), increased the time in bed without limb movements (p<0.0001), and improved subjective quality of sleep (p=0.0004). The onset of action was rapid after the first dose, and full efficacy was achieved within the first few days of therapy; these improvements disappeared immediately when treatment was discontinued. Levodopa/benserazide treatment was well tolerated and safe.\n Levodopa/benserazide is effective and safe in the treatment of RLS. Objective and subjective measures of sleep improved rapidly after the first dose. RLS symptoms recurred immediately after treatment was discontinued.", "We report the effects of a single bedtime dose of L-dopa 100-200 mg on sleep quality, frequency of periodic leg movements (PLM) and daily living in patients with idiopathic and uremic restless legs syndrome (RLS). Seventeen patients with idiopathic and 11 with uremic (on continuous hemodialysis) RLS were evaluated comparatively by polysomnography, actigraphy and subjective ratings in a randomized, controlled and double-blind crossover trial with L-dopa and placebo for 4 weeks each. Neurophysiologic assessments showed significant reduction of the number of periodic leg movements (p = 0.003) and the PLM-index (p = 0.005) most pronounced during the first 4 hours of bedtime after L-dopa (p = 0.001). Subjective evaluation confirmed improvement of sleep quality (p = 0.002) and showed significantly higher quality of life during daytime (p = 0.030) while the patients received L-dopa therapy. We conclude that L-dopa 100-200 mg proved to be effective in idiopathic RLS and for the first time under controlled conditions in uremic RLS without any severe side effects.", "Six patients with restless legs syndrome (RLS) and periodic movements during sleep (PMS) received placebo or L-dopa in a double-blind study. We recorded patients for 36 consecutive hours in the sleep laboratory during a baseline investigation and at the end of each treatment period. Daily evening questionnaires and a suggested immobilization test (SIT) performed at bedtime on each recording night documented the effect of L-dopa in RLS. A nocturnal EMG recording of the anterior tibialis muscles revealed the effect of L-dopa on PMS. L-Dopa proved effective in treating both RLS and PMS. Although not present in every patient, leg movements recorded during the SIT exhibited a clear periodicity. These observations support the hypothesis that RLS and PMS are two manifestations of the same central sensorimotor disorder.", "Sixteen patients with symptoms of restless legs syndrome and resulting insomnia are included in this study. They were nine women and seven men with a mean age of 50.8 years and with a mean duration of symptoms of 6.3 years. The purpose of the study is to determine the drugs that are useful for the treatment of restless legs syndrome. In 13 patients L-Dopa plus benserazide, in two patients bromocriptine, and in the remaining one patient piribedil were used orally at night approximately 1 h before bedtime. Compared with placebo these dopaminergic drugs decreased the times of waking up and staying awake periods at a statistically significant level (p changed between 0.025 and 0.01, t test). In this susceptibility of CNS there is dysfunction of the dopamine system triggered by sleep, and resting and dopaminergic potentiation by drugs affect the symptoms.", "We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline." ]

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[ "Calcium and low-dose aspirin prophylaxis in women at high risk of pregnancy-induced hypertension.", "Effect of low-dose aspirin on vascular refractoriness in angiotensin-sensitive primigravid women.", "Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications.", "Low-dose aspirin and hypertension in pregnancy.", "A prospective randomized placebo-controlled trial of low-dose aspirin for prevention of intra-uterine growth retardation.", "A randomized controlled trial of low-dose aspirin in women at risk from pre-eclampsia.", "A randomised trial of low dose aspirin for primiparae in pregnancy. The Jamaica Low Dose Aspirin Study Group.", "ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA (Estudo Colaborativo para Prevenção da Pré-eclampsia com Aspirina) Collaborative Group.", "The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies.", "Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.", "A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow.", "Low-dose aspirin improves fetal weight in umbilical placental insufficiency.", "Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial.", "Low-dose aspirin therapy to prevent preeclampsia.", "Low dose aspirin in prevention of pregnancy-induced hypertension in primigravidae at the Muhimbili Medical Center, Dar es Salaam.", "Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.", "Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14-16 weeks pregnancy: randomized controlled clinical trial.", "Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.", "Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches.", "A randomized placebo-controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non-pregnant women, in normal pregnancy, and in gestational hypertension.", "Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn.", "Prevention of fetal growth retardation with low-dose aspirin: findings of the EPREDA trial.", "Trial of prophylactic administration of TXA2 synthetase inhibitor, ozagrel hydrochloride, for preeclampsia.", "Administration time-dependent effects of aspirin in women at differing risk for preeclampsia.", "Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension.", "Time-dependent effects of low-dose aspirin administration on blood pressure in pregnant women.", "Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo-controlled, double-blind trial.", "Low-dose aspirin in primigravidae with positive roll-over test.", "Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial.", "Prevention of pregnancy-induced hypertension in twins by early administration of low-dose aspirin: a preliminary report.", "A study of use of low dose aspirin in prevention of pregnancy induced hypertension.", "Aspirin (100 mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 1).", "A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia.", "Prevention of pre-eclampsia by early antiplatelet therapy." ]

[ "The objectives of the study were to confirm the validity of using oscillometric measurement of MAP in the left lateral position to identify those at high risk for developing pregnancy-induced hypertension (PIH), and to assess and compare the efficacy of prophylaxis with low-dose aspirin or calcium supplementation in high-risk patients.\n A prospective study in pregnancy; 500 normotensive, primigravid Chinese women were recruited in the second trimester of pregnancy on the basis of 80 mm Hg > or = MAP < 106 mm Hg in the antenatal clinic. They were then screened by Dinamap in a research setting, measuring MAP in the left lateral position after rest and using a cutoff value of 60 mm Hg for inclusion in the randomized study. Randomization was divided into three groups: control, low-dose aspirin, and calcium supplementation. After delivery, patients were classified as either having remained normotensive or having developed PIH, with or without proteinuria.\n The incidence of both proteinuric and nonproteinuric PIH was significantly lower in patients screened out as low risk than in those selected as high risk using a critical value of 60 mm Hg for left lateral MAP (p < 0.05). The incidence of proteinuric PIH was significantly lower in patients given low-dose aspirin than in the control group (p < 0.05). However, the confidence intervals for the effect were wide, comparable with aspirin having no effect or leading to a 16-fold reduction in the risk of preeclampsia. For those given calcium supplementation, the reduction was not significant. There was no significant difference in the incidence of nonproteinuric PIH between the control group and the two groups receiving prophylaxis.\n Oscillometric measurement of second-trimester left lateral MAP is a valid predictor of proteinuric PIH. Low-dose aspirin may offer a degree of protection from proteinuric PIH in these high-risk women. Calcium supplementation was not shown to significantly reduce the incidence of PIH.", "The hypothesis that an enhanced vasopressor response to angiotensin II in pregnancy may be corrected by suppressing production of platelet thromboxane A2 with low-dose aspirin was tested in a randomized, placebo-controlled, double-blind trial. We studied 36 normotensive primigravid women with an elevated blood pressure response to intravenously infused angiotensin II at 28 weeks' gestation; 18 women received 60 mg of aspirin daily and the same number received matched placebo until 34 weeks' gestation, when angiotensin-sensitivity was again determined. In women taking aspirin, values of thrombin-induced platelet malondialdehyde production were approximately 10% of those determined in the placebo group, indicating marked suppression of thromboxane A2 synthesis. In the aspirin group vascular refractoriness to angiotensin II was restored in 14 of 17 treated women, by comparison with 5 of 15 women in the placebo group who had remained normotensive. These results support the hypothesis that prostacyclin/thromboxane imbalance is an important pathophysiologic factor in the development of the enhanced angiotensin-sensitivity associated with pregnancy-induced hypertensive disorders.", "To determine whether prophylactic, low dose controlled-release aspirin improves outcome for pregnant women and their babies in Barbados.\n Randomised placebo-controlled trial.\n The Queen Elizabeth Hospital, Barbados.\n All women attending antenatal clinics between 12 and 32 weeks of gestation were eligible, if without specific contraindications to aspirin and unlikely to deliver immediately.\n Randomisation was computer-generated in the antenatal clinic; 1822 women were allocated to receive 75 mg controlled-release aspirin and 1825 matching placebo.\n Proteinuric pre-eclampsia, other pregnancy-induced hypertension, pregnancy duration, birthweight, stillbirths and neonatal deaths, major neonatal events.\n All but three women from each group were followed up successfully. Forty-four percent were primigravid, and 8% had previous obstetric complications. There were no significant differences between the allocated treatment groups in the incidence of proteinuric pre-eclampsia (40 [2.2%] of those allocated aspirin, compared with 46 [2.5%] allocated placebo), of preterm delivery (255 [14.0%] vs 270 [14.8%]), of birthweight < 1500 g (32 [1.7%] vs 33 [1.8%]) or of stillbirth and neonatal death (44 [2.4%] vs 38 [2.1%]). Aspirin was not associated with excess risk of maternal or fetal bleeding.\n The results of this study in Barbados do not support the routine use of low dose aspirin for prevention of pre-eclampsia or its complications, confirming results of previous large trials in other settings.", "nan", "To evaluate the effects of low-dose aspirin on placental circulation and on the prevention of intrauterine growth retardation (IUGR).\n We conducted a prospective randomized, double blind, controlled clinical trial in 84 pregnant women (mainly nulliparous women) at high risk of IUGR. From the 28th-30th week of gestation onward, low dose aspirin (75 mg daily, study group, n = 40) or placebo (control group, n = 44) was given consecutively for 6 to 8 weeks. Pulse-wave umbilical artery Doppler velocimetry was measured before and after drug use.\n The mean value of systolic/diastolic ratio of umbilical artery flow velocity waveforms in the study group was significantly lower than that in the control group after drug use, but there was no difference between the two groups before drug use. The incidences of IRGR and preeclampsia in the study group (7.5% and 10.0% respectively) were significantly lower than those in the control group (27.3% of both). No adverse effects of low dose aspirin on both mother and fetus were observed.\n Low dose aspirin administration (75 mg daily) beginning at the early stage of third trimester may improve the fetoplacental circulation, and thus prevent IUGR and/or preeclampsia effectively.", "To determine whether low-dose aspirin reduces the incidence of pre-eclampsia, reduces perinatal mortality and improves birth weights in pregnant women considered at high risk of developing pre-eclampsia.\n Two-hundred fifty subjects were recruited from the antenatal clinics at Harare Central Hospital with either a previous history of pregnancy-induced hypertension or pre-existing chronic hypertension and were randomized to receive either 75 mg of aspirin (ASA) or placebo (PLA).\n Two-hundred thirty subjects (ASA, n = 113; PLA, n = 117) completed the trial. The odds of developing pre-eclampsia for those on aspirin was 0.72 times those on placebo (95% CI, 0.34-1.52). The mean birth weight was 2774 g for those on aspirin and 2694 g for those on placebo (P = 0.80). No difference was noted in the perinatal deaths (OR = 0.38; 95% CI, 0.10-1.20).\n Prophylactic use of aspirin was not associated with a significant effect on the major pregnancy outcomes assessed in this study.", "To investigate whether low dose aspirin medication given to primiparous women provides benefit in preventing pre-eclampsia or intrauterine growth retardation.\n Randomised double-blind controlled trial of low dose aspirin and placebo in pregnancy.\n Residents of the parishes of Kingston and St Andrew, Jamaica; 6275 primiparae enrolled between 12 and 32 weeks of gestation.\n Hypertensive disorders of pregnancy (including pre-eclampsia and eclampsia), preterm delivery, and low birthweight. In addition, to assess whether enrollment early, rather than late had more beneficial effect. Possible adverse effects on the woman and her infant were monitored.\n Of enrolled primiparae, 97% were followed throughout pregnancy. There were no differences between those on aspirin and those on placebo in the development of hypertensive disorders (e.g. for a rise in diastolic pressure of 25 mmHg the odds ratio [OR] was 1.02 [95% CI 0.86-1.21]; for proteinuric pre-eclampsia OR 1.15 [95% CI 0.92-1.44]; eclampsia OR 0.82 [95% CI 0.44-1.53]); except for oedema which was significantly less prevalent in those on aspirin (OR 0.85 [95% CI 0.75-0.96]). Women on aspirin were no significantly less likely to deliver preterm (OR 0.93 [95% CI 0.79-1.09]) or have a larger fetus (mean birthweight difference 18 g [95% CI -9 to 45]). They were, however, significantly more likely to suffer from bleeding disorders antenatally, intrapartum and postpartum; for postpartum haemorrhage OR 1.40 (95% CI 1.13-1.73).\n This trial shows that low dose aspirin has no consistent beneficial effect in primiparae.", "To determine the effectiveness of low dose aspirin in women at high risk of adverse outcomes associated with pre-eclampsia.\n A collaborative randomised trial comparing the effects of low dose aspirin (60 mg) with placebo on pre-eclampsia and other materno-fetal complications associated with hypertension.\n Twelve teaching maternity hospitals and 182 obstetricians' offices in Brazil.\n One thousand and nine women considered to be at high risk for the development of pre-eclampsia, or its complications, entered the study between 12 and 32 weeks of gestation. They were randomly allocated to receive aspirin (498 women) or placebo (511 women) until delivery, and follow up was obtained for 96%.\n There were no significant differences between the treatment groups in the incidence of proteinuric pre-eclampsia (6.7% aspirin-allocated compared with 6.0% placebo-allocated women), of preterm delivery (22.3% compared with 26.1%), of intrauterine growth retardation (8.5% compared with 10.1%), or of stillbirth and neonatal death (7.3% compared with 6.0%), nor were there significant differences in the incidence of proteinuric pre-eclampsia in any subgroup of women studied, including those who had systolic blood pressures of 120 mmHg or above at entry (8.5% compared with 7.3%) or those who were chronically hypertensive (10.0% compared with 7.1%). Aspirin was not associated with a significant excess of maternal or fetal bleeding.\n The results of this study do not support the routine prophylactic administration of low dose aspirin in pregnancy to any category of high risk women (even those who have chronic hypertension or who are considered to be especially liable to early onset pre-eclampsia).", "We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for pre-eclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A2 to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pregnancy-induced hypertension and pre-eclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin.", "Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.", "To evaluate color Doppler imaging of the uterine arteries as a screening test in nulliparous women, and to examine the role of low-dose aspirin therapy in pregnancies with abnormal uteroplacental resistance.\n At the routine 18-week fetal morphology ultrasound scan, 955 nulliparous women underwent color Doppler imaging of the uterine arteries. Abnormal uteroplacental vascular resistance was defined with respect to both the systolic-diastolic ratio of the flow velocity waveform and the presence of an ipsilateral early diastolic notch. Those with abnormal uterine artery waveforms were asked to participate in a randomized controlled trial of aspirin therapy. Pregnancy outcomes were compared in women with normal or abnormal flow velocity waveforms, as well as in the two arms of the intervention study.\n Of 186 women with abnormal uteroplacental resistance according to criteria defined previously, 102 agreed to randomization to either low-dose aspirin (100 mg/day) or placebo for the remainder of the pregnancy. Abnormal uterine artery flow velocity waveforms were associated with statistically significant increases in preeclampsia (11 versus 4%), birth weight below the tenth percentile (28 versus 11%), and adverse pregnancy outcome (45 versus 28%). Prophylactic aspirin therapy did not result in a significant reduction in pregnancy complications.\n Abnormal uteroplacental resistance at 18 weeks' gestation was associated with a significant increase in adverse pregnancy outcome. Low-dose aspirin did not reduce pregnancy complications in women with uteroplacental insufficiency.", "nan", "We identified 19 women who had persistently positive test results for antiphospholipid antibodies who were considered to be at low risk because they had none of the associated signs or symptoms of the antiphospholipid antibody syndrome. They had had no (10/19, 53%) or just one prior spontaneous abortion and did not have a history of thrombosis or thrombocytopenia. Many (8/19, 42%) had had a prior uncomplicated pregnancy ending in a live birth. These women were randomly assigned to receive low-dose aspirin (81 mg daily) or usual care. There were few obstetric complications recorded in either treatment group. One woman in the aspirin group had a fetal death, and one in the usual care group had a low-birth-weight infant. The frequency of complications was so low that > 600 such women would need to be entered into a randomized trial to evaluate whether low-dose aspirin would be beneficial treatment during a pregnancy. We concluded that treatment of pregnant women with antiphospholipid antibodies who are otherwise at low risk cannot be justified on the basis of the available evidence.", "Our aim was to test the hypothesis that acetylsalicylate (aspirin) treatment reduces the incidence or severity of pregnancy-associated hypertension.\n Patients were nulliparous, healthy, and with a singleton gestation at between 20 and 22 weeks' gestation. A sample size of 600 patients was calculated on the basis of p < or = 0.05 and 90% power of observation. A 2-week placebo-controlled \"run-in\" was used to select compliant patients. Randomization occurred at 24 weeks, with 60 mg of aspirin or placebo treatment from randomization to delivery.\n Follow-up was maintained on 99% of the patients. The randomized patients had a 94% pill compliance index. At randomization, serum thromboxane medians were similar in both groups. Thromboxane B2 levels in the aspirin group decreased significantly from baseline at 29 to 31 weeks, 34 to 36 weeks, and at delivery as compared with an overall increase in the placebo group. Preeclampsia developed in five of 302 women (1.7%) who received aspirin versus 17 of 302 (5.6%) who received the placebo (p = 0.009). Preeclampsia was severe in one aspirin and in six placebo recipients (p = 0.06).\n Daily ingestion of 60 mg of aspirin beginning at 24 weeks' gestation significantly reduced the occurrence of preeclampsia.", "There is evidence that aspirin in low doses favourably influences the course and outcome of pregnancy in women at risk of developing pregnancy-induced hypertension. We conducted a double blind prospective randomized study to investigate the effect of low dose aspirin in preventing pregnancy-induced hypertension. Two hundred and one primigravidae from twenty weeks of pregnancy and above were screened using the roll-over test. Of the 127 women with an increase in blood pressure during the roll-over test, 126 women entered the study and were treated with a daily dose of either aspirin (80 mg) or placebo up to 10 days before the expected date of delivery. Samples of urine were collected for detection of aspirin. The incidence of pregnancy-induced hypertension in the aspirin treated group was significantly lower than in the placebo treated group; 3.17% versus 15.9% with a p value of 0.02. It is concluded that low daily doses of aspirin taken from twenty weeks of pregnancy significantly reduce the incidence of pregnancy-induced hypertension, possibly through the correction of an imbalance in levels of thromboxane and prostacyclin.", "Whether low-dose aspirin prevents preeclampsia is unclear. It is not recommended as prophylaxis in women at low risk for preeclampsia but may reduce the incidence of the disease in women at high risk.\n We conducted a double-blind, randomized, placebo-controlled trial in four groups of pregnant women at high risk for preeclampsia, including 471 women with pregestational insulin-treated diabetes mellitus, 774 women with chronic hypertension, 688 women with multifetal gestations, and 606 women who had had preeclampsia during a previous pregnancy. The women were enrolled between gestational weeks 13 and 26 and received either 60 mg of aspirin or placebo daily.\n Outcome data were obtained on all but 36 of the 2539 women who entered the study. The incidence of preeclampsia was similar in the 1254 women in the aspirin group and the 1249 women in the placebo group (aspirin, 18 percent; placebo, 20 percent; P=0.23). The incidences in the aspirin and placebo groups for each of the four high-risk categories were also similar: for women with pregestational diabetes mellitus, the incidence was 18 percent in the aspirin group and 22 percent in the placebo group (P=0.38); for women with chronic hypertension, 26 percent and 25 percent (P= 0.66); for those with multifetal gestations, 12 percent and 16 percent (P=0.10); and for those with preeclampsia during a previous pregnancy, 17 percent and 19 percent (P=0.47). In addition, the incidences of perinatal death, preterm birth, and infants small for gestational age were similar in the aspirin and placebo groups.\n In our study, low-dose aspirin did not reduce the incidence of preeclampsia significantly or improve perinatal outcomes in pregnant women at high risk for preeclampsia.", "To assess the effectiveness of low-dose aspirin in the prevention of preeclampsia and intrauterine growth restriction (IUGR) in high-risk pregnant women with abnormal findings at uterine artery Doppler velocimetry performed at 14-16 weeks.\n Randomized controlled clinical trial.\n Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Egypt.\n The trial enrolled 139 women at risk of preeclampsia or IUGR, with abnormal uterine artery Doppler findings that included the presence of unilateral or bilateral diastolic notch, high resistance index (RI), or high pulsatility index (PI) at 14-16 weeks of gestation. The women were randomly allocated into two groups, one receiving aspirin since admission to hospital (n=74) and the other serving as control (n=65). All women were followed up until delivery to assess maternal and perinatal outcomes. T-test was used for comparison of quantitative variables, and categorical variables were compared by chi2 test. OUTCOME CRITERIA: Development of mild or severe preeclampsia, time of onset of preeclampsia, preterm delivery, and the development of IUGR.\n Preeclampsia developed in 35% of women receiving aspirin and 62% of women in the control group (P=0.003), with severe preeclampsia developing in 8% and 23% of women (P=0.215), respectively. Preeclampsia before 37 weeks of gestation was recorded in only 4% of women receiving aspirin as opposed to 83% of controls (P<0.001). In the group of women receiving aspirin, 19% of newborns suffered from IUGR as opposed to 32%of newborns in the control group (P=0.106). There was no significant difference between the two groups in the rate of preterm delivery (P=0.080), mode of delivery (P=0.971), Apgar score <5 after one minute (P=0.273) and after 5 minutes (P=0.941), maternal or neonatal bleeding (P=0.948), and neonatal birth weight (P=0.399).\n Low-dose aspirin administered as early as 14-16 weeks of gestation to pregnant women at high risk of preeclampsia with abnormal uterine Doppler findings may reduce or modify the course of severe preeclampsia. Its effects on the prevention of IUGR need further evaluation.", "Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known.\n We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity.\n Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01).\n Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae.", "To evaluate the efficacy of low-dose acetylsalicylic acid in the prevention of pregnancy-induced hypertension and intrauterine growth retardation in high-risk pregnancies as determined by transvaginal Doppler ultrasound study of the uterine arteries at 12 to 14 weeks of gestation.\n Randomised, double blind and placebo-controlled trial.\n The Department of Obstetrics and Gynaecology, Tampere University Hospital, Finland.\n One hundred and twenty pregnant women considered to be at high risk of pre-eclampsia or intrauterine growth retardation were screened by transvaginal Doppler ultrasound at 12 to 14 weeks of gestation.\n Ninety pregnant women with bilateral notches in the uterine arteries were randomised to receive acetylsalicyclic acid 0.5mg/kg/day (n = 45) or placebo (n = 45) from 12 to 14 weeks of gestation.\n Hypertensive disorders of pregnancy and intrauterine growth retardation.\n Forty-three women on acetylsalicyclic acid and 43 on placebo were successfully followed up. The use of acetylsalicyclic acid was associated with a statistically significant reduction in the incidence of pregnancy-induced hypertension (11.6% vs 37.2%, RR = 0.31, 95% CI 0.13-0.78) and pre-eclampsia (4.7% vs 23.3%, RR = 0.2, 95% Cl 0.05-0.86). The incidence of hypertension before 37 weeks of pregnancy was also significantly reduced (2.3% vs 20.9%, RR = 0.22, 95% CI 0.05-0.97). The reduction in the incidence of intrauterine growth retardation (2.3% vs 7%) was not statistically significant. Acetylsalicyclic acid was not associated with excess risk of maternal or fetal bleeding.\n In women rated in Doppler velocimetry waveform analysis to be at high risk of pre-eclampsia, low-dose acetylsalicyclic acid reduces the incidence of pregnancy-induced hypertension and especially proteinuric pre-eclampsia.", "To investigate the effect of 60 mg aspirin daily on platelet reactivity and prostaglandin production in various groups of patients. Similar regimens, which are thought to act through inhibition of platelet thromboxane production, are currently undergoing clinical assessment for the prevention of pre-eclampsia and intrauterine growth retardation.\n A prospective randomized placebo controlled study.\n University Hospital, Nottingham.\n 12 non-pregnant female volunteers, 18 normal primigravidae before 16 weeks gestation and 16 pregnant women admitted with gestational hypertension (GH) at a mean gestation of 38 weeks.\n In the non-pregnant women blood samples were taken before and after a 10-day course of 60 mg aspirin daily. The primigravidae had blood samples taken at 16 weeks and then they were randomized to receive either 60 mg aspirin daily or a matched placebo. Further blood samples were obtained at 28, 32 and 36 weeks.\n Changes in platelet reactivity and release reaction, and serum thromboxane production, were estimated in whole blood.\n 60 mg aspirin daily significantly inhibited cyclo-oxygenase dependent platelet aggregation, release reaction and serum thromboxane production in non-pregnant and pregnant women, and in women with GH (P less than 0.01). When adrenaline was used as the aggregating agent, the cyclo-oxygenase pathway was recruited in the increased reactivity seen in the third trimester of normal pregnancy, and was sensitive to inhibition by low dose aspirin.\n Low dose aspirin would appear to be an appropriate agent for the inhibition of platelet reactivity associated with hypertensive pregnancy.", "To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants.\n Placebo controlled prospective study.\n Departments of Obstetrics and Gynaecology, University of Helsinki, University of Oulu and Central Hospital of Middle Finland, Finland.\n Two hundred and eight pregnant women with pre-existing hypertension or a history of severe preeclampsia in their previous pregnancy. Prostanoids were studied in a subgroup of 18 women.\n The women were randomised to receive ASA (50 mg/day, n = 103) or placebo (n = 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre-existing hypertension or the appearance of hypertension in previously normotensive women, the appearance of proteinuria and fetal growth were the main end points, but some other clinical characteristics were also recorded. Urinary excretion of PGI2 and TxA2 metabolites by mothers and infants and their production in umbilical arteries in vitro were also studied.\n Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal anencephaly (ASA group). In addition, seven women discontinued the treatment due to urticaria (two women in ASA group), increased activity of aspartate amino transferase in serum (one woman in both groups), or increased bleeding time (one woman in ASA group, two women in placebo group), and one woman in the placebo group was lost from follow-up. Thus the end points could be assessed in 97 women taking ASA and 100 women taking placebo. ASA did not diminish the rate of the rise of blood pressure without (12 vs 14, respectively) or with proteinuria (9 vs 11), but fetal haemodynamic disturbances as assessed by Doppler equipment (1/44 vs 6/45 women studied, P = 0.05) and need for treatment in neonatal intensive care unit (10 vs 21, P = 0.04) were more rare in ASA group. ASA tended to increase the birthweight of the newborn (3348 +/- 707 g vs 3170 +/- 665 g, mean +/- SD, P = 0.07), but two perinatal deaths occurred in ASA group. ASA prolonged the bleeding time of the mother (435 s, 210-998 s (geometric mean, range) vs 349 s, 210-690 s, P = 0.02), but caused no extra blood loss during delivery, nor affected neonatal hemostasis. In a subgroup of mothers (ASA, n = 10; placebo, n = 8), ASA inhibited more than 90% of platelet TxA2-production, and caused a 65 to 80% decrease in the urinary excretion of TxA2 metabolites, but no decrease in the urinary excretion of PGI2 metabolites.\n ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neonatal care. It inhibited strongly maternal thromboxane A2 but not PGI2 production and thus shifted the balance between PGI2/TxA2 to the dominance of the vasodilatory, anti-aggregatory side.", "The efficacy of low-dose aspirin in preventing fetal growth retardation was tested in a randomised, placebo-controlled, double-blind trial. A secondary aim was to find out whether dipyridamole improves the efficacy of aspirin. 323 women at 15-18 weeks' amenorrhoea were selected at twenty-five participating centres on the basis of fetal growth retardation and/or fetal death or abruptio placentae in at least one previous pregnancy. They were randomly allocated to groups receiving placebo, 150 mg/day aspirin, or 150 mg/day aspirin plus 225 mg/day dipyridamole, for the remainder of the pregnancy. In the first phase of the trial all actively treated patients (n = 156) were compared with the placebo group (n = 73). Mean birthweight was significantly higher in the treated than in the placebo group (2751 [SD 670] vs 2526 [848] g; difference 225 g [95% CI 129-321 g], p = 0.029) and the frequency of fetal growth retardation in the placebo group was twice that in the treated group (19 [26%] vs 20 [13%]; p less than 0.02). The frequencies of stillbirth (4 [5%] vs 2 [1%]) and abruptio placentae (6 [8%] vs 7 [5%]) were also higher in the placebo than in the treated group. The benefits of aspirin treatment were greater in patients with two or more previous poor outcomes than in those with only one. In the second analysis, of aspirin only (n = 127) vs aspirin plus dipyridamole (n = 119), no significant differences were found. There was no excess of maternal or neonatal side-effects in the aspirin-treated patients.", "In an attempt to investigate the prophylactic effect of a thromboxane A2 (TXA2) synthetase inhibitor on pregnant women with a high risk of preeclampsia, the following clinical study was undertaken.\n Forty pregnant women were randomly allocated to control or treatment groups. Ozagrel Hydrochloride (400 mg/day, orally) and placebo were started at 20 weeks of gestation and continued until delivery.\n Seventeen of 20 (85%) women in the control group developed preeclampsia, whereas 9 of 20 (45%) in the treatment group developed preeclampsia. Ozagrel Hydrochloride significantly (p < 0.01) reduced the occurrence of preeclampsia, and the incidence of both hypertension (p < 0.05) and proteinuria (p < 0.01) was significantly less in the treatment group compared with the control group. One month after administration, the mean plasma concentration of TXB2, a metabolite of TXA2, was significantly decreased (p < 0.01) to 62.4 +/- 13.6%, whereas that of 6-keto prostaglandin F1 alpha, a metabolite of PGI2, was significantly increased (p < 0.01) to 206.7 +/- 52.8%. There were no maternal or fetal side effects observed.\n It seems likely that Ozagrel Hydrochloride could be used for the prevention of preeclampsia in high-risk pregnant women.", "This study extends previous results on the effects of low-dose aspirin on blood pressure in pregnant women at differing risk of developing hypertension in pregnancy and who received aspirin at different times according to their rest-activity cycle. A double-blind, randomized, placebo-controlled trial was conducted in 240 pregnant women randomly assigned to 1 of 6 groups according to treatment (placebo or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure and heart rate for each subject were automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 to 8 weeks after delivery). Subjects were further divided for comparative purposes according to the results of the tolerance-hyperbaric test for early identification of those with a higher risk for developing hypertensive complications in pregnancy. Results indicated that there was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was, however, highly statistically significant at time 2 and, to a greater extent, at time 3 (mean reductions of 14.2 and 9.6 mm Hg in 24-hour means for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). Effects of aspirin on blood pressure were significantly larger for women with a positive test at the time of recruitment (P<0.001). Differences in blood pressure among pregnant women receiving aspirin at different times in the circadian cycle disappeared at puerperium (P>0.212). There was no effect of aspirin or placebo on heart rate. This study corroborates the statistically significant, time-dependent effect of low-dose aspirin on blood pressure in pregnant women with differing risk of developing hypertensive complications in pregnancy. Although the mechanism involved in the administration-time-dependent responsiveness of blood pressure to aspirin still remains uncertain, the use of doses of aspirin <80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks' gestation, and the lack of circadian timing for aspirin administration could all explain the lack of positive results in previous clinical trials.", "There is evidence that aspirin in low doses favorably influences the course of pregnancy-induced hypertension, but the mechanism, although assumed to involve suppression of the production of thromboxane by platelets, has not been established. We performed a randomized study of the effect of the long-term daily administration of 60 mg of aspirin (n = 17) or placebo (n = 16) on platelet thromboxane A2 and vascular prostacyclin in women at risk for pregnancy-induced hypertension. Low doses of aspirin were associated with a longer pregnancy and increased weight of newborns. Serum levels of thromboxane B2, a stable product of thromboxane A2, were almost completely (greater than 90 percent) inhibited by low doses of aspirin. The urinary excretion of immunoreactive thromboxane B2 was significantly reduced without changes in the level of 6-keto-prostaglandin F1 alpha, a product of prostacyclin. Mass spectrometric analysis showed that aspirin reduced the excretion of the 2,3-dinor-thromboxane B2 metabolite--mainly of platelet origin--by 81 percent and of thromboxane B2, probably chiefly of renal origin, by 59 percent. The urinary excretion of 6-keto-prostaglandin F1 alpha and of its metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha was not affected. Low doses of aspirin only partially (63 percent) reduced neonatal serum thromboxane B2. No hemorrhagic complications were observed in the newborns. Thus, in women at risk for pregnancy-induced hypertension, low doses of aspirin selectively suppressed maternal platelet thromboxane B2 while sparing vascular prostacyclin, but only partially suppressed neonatal platelet thromboxane B2, allowing hemostatic competence in the fetus and newborn.", "This study investigated the effects of low-dose acetylsalicylic acid (aspirin) on blood pressure in pregnant women who were at risk of developing gestational hypertension or preeclampsia and who received aspirin at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 100 pregnant women. Blood pressure for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery. Women were randomly assigned to one of six groups according to treatment (placebo, 50 subjects or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Results indicated that there was (1) no effect on blood pressure from placebo at any time (P>.212) and (2) a highly statistically significant (P<.001) time-dependent effect on blood pressure from aspirin. There was no effect of aspirin on blood pressure at time 1 (compared with placebo), but the blood pressure reduction was highly statistically significant after time 2 and, to a greater extent, after time 3 (mean reduction of 12 and 8 mm Hg in 24 hours for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). These time-dependent effects of aspirin on blood pressure should be taken into account for the optimization of long-term aspirin administration at low doses for prevention of preeclampsia. In any meta-analysis of aspirin effects, inquiries about the time when the subjects took the drug are indicated and may account for discrepancies in the literature.", "This study was conducted to evaluate uteroplacental and fetal hemodynamics in fetuses exposed to low-dose aspirin (100 mg/d).\n Randomized, placebo-controlled, double-blind trial.\n The study protocol included singleton pregnancies of less than 20 gestational weeks at risk for pre-eclampsia or fetal growth restriction. Exclusion criteria were diabetes mellitus, pre-existing proteinuric hypertension or fetal malformations. Forty-three pregnant women were randomly allocated to daily treatment with 100 mg aspirin (n = 22) or placebo (n = 21).\n Pulsed Doppler measurements of the uterine artery, fetal middle cerebral artery, fetal aorta, ductus arteriosus and atrioventricular valves were performed longitudinally at 14 day intervals starting from 18 gestational weeks until delivery. Results were expressed as group medians (aspirin vs. placebo) and were analyzed by Mann-Whitney U-test.\n There was no difference in uterine, umbilical, aortic, middle cerebral and ductus arteriosus blood flow between the aspirin group and controls. Median ductal peak flow velocities increased with gestational age in both groups, but differences between groups did not reach significance. In the third trimester of pregnancy, ductal peak velocities > 140 cm/s were occasionally observed in both groups. However, end diastolic velocities > 35 cm/s or atrioventricular valve regurgitation never occurred.\n Daily administration of low-dose aspirin during the second and third trimesters of pregnancy does not alter uteroplacental or fetoplacental hemodynamics and does not cause moderate or severe constriction of the ductus arteriosus.", "In a prospective, randomized, double-blind study for the prevention of pregnancy-induced hypertension and preeclampsia, 41 primigravidae with positive roll-over test (28th-32nd week of pregnancy) received 80 mg aspirin/day or placebo until the end of the 37th week. In the patients treated with acetylsalicylic acid (n = 22), 3 cases of proteinuria occurred, but no hypertensive pregnancy complication. In the placebo group (n = 19), 10 patients developed pregnancy-induced hypertension (6 of them preeclampsia). Group-specific differences concerning the occurrence of hypertension were statistically highly significant (p = 0.0004). No relevant differences were observed with regard to pregnancy duration, birth weight and umbilical artery pH value. The placebo group included 1 intrauterine death. No increased tendency to maternal or fetal bleeding was noticed.", "The purpose of this study was to investigate the hypothesis that maternal administration of 100mg aspirin each day will improve birth-weight and other measures of neonatal size when given as a treatment to pregnancies complicated by fetal growth restriction and umbilical-placental insufficiency. A randomized, double-blind, placebo controlled study design was employed; 51 pregnant women were enrolled. The entry criteria were a fetal abdominal circumference < 10th per centile together with an umbilical artery Doppler systolic/diastolic ratio > 95th per centile between 28 and 36 weeks' gestation. Compliance was assessed by serial measurement of maternal serum thromboxane B2 levels. The mean gestational age at enrolment was 32 weeks and at delivery was 36 weeks. There were no differences between the 2 groups in gestational age at birth; birth-weight or birth-weight ratio; circumferences of the head, chest or abdomen; skin fold thicknesses; or neonatal morbidity. Low dose aspirin therapy did not alter Doppler systolic/diastolic ratios. After 14 days therapy, mean thromboxane B2 levels fell more than 80% from baseline values; 10.5% of women did not demonstrate biochemical confirmation of aspirin ingestion, despite verbal confirmation of compliance. We conclude that low dose aspirin therapy is not of benefit in the treatment of pregnancies complicated by fetal growth restriction and umbilical-placental insufficiency between 28 and 36 weeks' gestation.", "Effectiveness of early administered low-dose aspirin in prevention of pregnancy-induced hypertension (PIH) and fetal growth retardation in twin pregnancies was investigated in a randomized placebo controlled, double-blind trial in 47 twin pregnancies.\n Twenty-four women received 100 mg of aspirin daily from mean gestational age of 17.7 wk, and 23 women ingested placebo from a mean gestational age of 18 wk until delivery. The placebo and aspirin group were similar in age, weight gain, zygosity, gravidity, parity, and obstetrical antecedents. Treatment lasted for a mean period of 16.8 wk and 18.3 wk in the placebo and aspirin groups, respectively. The mean gestational age at birth was 35.0 wk and 36.4 wk in the placebo and aspirin groups, respectively.\n PIH was noted in six women (26%) in the placebo group, but in only one woman (4%) in the aspirin treated patients (P < .05). The mean combined fetal weights of both twins, and the mean weight of the second twin at delivery were significantly higher in the aspirin treated mothers than in the placebo treated gravidas (mean difference of 781 g, P < .02 and mean difference of 488 g, P < .005, respectively). Intrauterine growth retardation (< 10th percentile) concerned 11 (24%) and six (13%) fetuses in the placebo and aspirin groups, respectively. No adverse effects of treatment to either the mothers or the infants were noted.\n Low-dose aspirin reduces the incidence of PIH and has a beneficial effect on fetal growth in twin pregnancies. Additional clinical trials are needed in order to define and select subgroups of twins where aspirin treatment is recommended.", "Forty-six nulliparous women in third trimester of pregnancy with a raised blood pressure of 30 mm Hg (systolic) or/and 15 mm Hg (diastolic) or both, over baseline values were treated with 75 mg of aspirin per day. The results are compared with another 48 age, height, weight, and gestational period matched nulliparaous women with similar condition for trial selection, who were treated as control. There is considerable more number of cases in the control group than in aspirin treated group showing subsequent rise of BP, appearance of proteinuria, and severe pre-eclamptic toxaemia. The aspirin treated group showed increased mean gestational age at termination 39.4 +/- 2.6 weeks as against 38.2 +/- 3.4, increased foetal weight 2860 +/- 552 g as against 2540 +/- 720 g. No case of neonatal haemorrhagic manifestations or congenital malformations were seen. However not much result is obtained with aspirin therapy in cases with established pregnancy induced hypertension or with proteinuria. Hence it is concluded that aspirin therapy should be given to prevent pregnancy induced hypertension. As predictability of other screening tests are not unequivocal, criterion used in this series for screening may be used.", "To reduce the incidence of pre-eclampsia in nulliparous women, in accordance with the suggestion of a recent meta-analysis that low dose aspirin might decrease this incidence by more than half if used early enough in and at a sufficient dose during pregnancy (more than 75 mg).\n Multicentre randomised double-blinded placebo-controlled trial.\n Twenty eight centres in Northern of France and one in Belgium.\n Three thousand and two hundred ninety-four nulliparous women recruited between 14 and 20 weeks.\n Randomisation to either 100 mg aspirin or placebo daily from inclusion through 34 weeks.\n Preeclampsia was defined as hypertension (> or =140 and or 90 mmHg) associated with proteinuria (> or =0.5 g/L).\n The aspirin (n = 1644) and placebo (n = 1650) groups did not differ significantly in the mothers' incidence of pre-eclampsia (28 of 1632 [1.7%] vs 26 of 1637 [1.6%]; relative risk, RR, 1.08, 95% CI 0.64-1.83), hypertension, HELLP syndrome or placental abruption, or in the children's incidence of perinatal deaths or birthweight below the 10th centile. The incidence of babies with birthweight below the third centile was significantly higher in the aspirin group, with no explanation. The incidence of maternal side effects was higher in the aspirin group, principally because of a significantly higher rate of haemorrhage.\n Aspirin at a dose of 100 mg does not reduce the incidence of pre-eclampsia in nulliparous women. Aspirin (100 mg) is associated with an increase in bleeding complications.", "To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition.\n Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up.\n The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%).\n These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR.", "102 patients at high risk of pre-eclampsia and/or fetal growth retardation were randomly allocated to treatment with 300 mg dipyridamole and 150 mg aspirin daily from 3 months' gestation onwards (group A) or to the control group (group B, no treatment). Group A was twice as likely as group B to have a normal pregnancy. Pre-eclampsia occurred in 6 patients in group B and none in group A. Major complications (fetal death or severe growth retardation) occurred in 9 patients in group B and none in group A. Platelet count and plasma volume were significantly higher in group A than in group B throughout pregnancy. The treatment did not produce serious adverse effects. Antiplatelet therapy given early in pregnancy to high-risk patients may thus protect against pre-eclampsia and fetal growth retardation." ]

[ "11659248", "9104380", "15035248" ]

[ "Information disclosure, subject understanding, and informed consent in psychiatric research.", "Evaluating the benefits of a patient information video during the informed consent process.", "Improving informed consent: a comparison of four consent tools." ]

[ "nan", "The study objective was to evaluate the effect of a patient information video during the informed consent process of a perinatal trial. Ninety women, between 19 and 33 weeks gestation, were randomised to receive written information about this perinatal trial and watch an information video or to receive written information only. Participants completed a questionnaire immediately after entry and 2-4 weeks later assessing knowledge of; feelings about the worth of; and willingness for future participation in the perinatal trial. When initially asked, more women who watched the video thought they would consent to the study (chi 2 = 6.3; df = 1; P = 0.01). No differences in knowledge about the perinatal trial were found initially, but 2-4 weeks later more knowledge had been retained by women who had watched the video (chi 2 = 6.7; df = 1; P = 0.01). These results suggest that a patient information video combined with an information sheet may result in greater participation in a research trial and may increase women's knowledge of a specific health problem and related research trial.", "nan" ]

[ "6371871", "211983", "354331", "6120655", "1253596", "2282421", "3555385", "4011672", "6437365", "241609", "3549879", "4566388", "24982", "3368545", "4711886", "373006", "2575796", "6133287", "227340", "406212", "7076630", "3933035", "5565254", "98127", "9152099", "4599422", "825356", "4608506", "692838", "6114503", "6349256", "3322467", "1487623", "7393998", "11760", "6347119", "28102", "22515", "224958", "3415422", "7093596", "7172160", "4871473", "4912332", "4576449" ]

[ "A double-blind, controlled clinical trial of haloperidol decanoate and fluphenazine decanoate in the maintenance treatment of schizophrenia.", "Drug and family therapy in the aftercare of acute schizophrenics.", "Double-blind therapeutic evaluation of fluspirilene compared with fluphenazine decanoate in chronic schizophrenics.", "Fluphenazine enanthate and fluphenazine decanoate in the treatment of schizophrenic outpatients: extrapyramidal symptoms and therapeutic effect.", "Comparison of depot fluphenazines: duration of action and incidence of side effects.", "Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical and social outcome at two years.", "Low- and conventional-dose maintenance therapy with fluphenazine decanoate. Two-year outcome.", "Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months' treatment for relapse prevention.", "Costs and benefits of two doses of fluphenazine.", "A comparative study with pipothiazine palmitate and fluphenazine enanthate in the treatment of schizophrenic patients.", "Weight gain and prolactin levels in patients on long-term antipsychotic medication: a double-blind comparative trial of haloperidol decanoate and fluphenazine decanoate.", "Depot phenothiazine treatment in acute psychosis: a sequential comparative clinical study.", "How schizophrenic patients change during 3 years' treatment with depot neuroleptics.", "Family attitudes and patient social adjustment in a longitudinal study of outpatient schizophrenics receiving low-dose neuroleptics: the family's view.", "Fluphenazine decanoate trial in chronic in-patient schizophrenics failing to absorb oral chlorpromazine.", "Depot fluphenazine in the prevention of relapse in schizophrenia: evaluation of a treatment regimen [proceedings].", "A comparative study of pipothiazine palmitate and fluphenazine decanoate in the maintenance of remission of schizophrenia.", "A double-blind comparative trial of the decanoates of clopenthixol and fluphenazine in the treatment of chronic schizophrenic out-patients.", "Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride.", "Clinical and social comparison of fluphenazine decanoate and flupenthixol decanoate in the community maintenance therapy of schizophrenia.", "Double-blind placebo substitution: withdrawal of fluphenazine decanoate in schizophrenic patients.", "Early unwanted effects of fluphenazine esters related to plasma fluphenazine concentrations in schizophrenic patients.", "EEG changes after fluphenazine enanthate and decanoate based on analog power spectra and digital computer period analysis.", "Long-acting oral vs injectable antipsychotic drugs in schizophrenics: a one-year double-blind comparison in multiple episode schizophrenics.", "Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment.", "Controlled trial of depot fluphenazine in out-patient schizophrenics.", "Speed and rate of remission in acute schizophrenia: a comparison of intramuscularly administered fluphenazine HC1 with thiothixene and haloperidol.", "A multicenter controlled trial of fluspirilene and fluphenazine enanthate in chronic schizophrenic syndromes.", "Fluphenazine decanoate and fluphenazine enanthate in the out-patient management of chronic schizophrenia.", "Clinical blood chemistry values and long acting phenothiazines.", "Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology.", "Haloperidol decanoate v. fluphenazine decanoate as maintenance therapy in chronic schizophrenic in-patients.", "Positive and negative symptoms, depression and social disability in chronic schizophrenia: a comparative trial of bromperidol and fluphenazine decanoates.", "[Drug-response differences of high and standard dosage of fluphenazine-decanoate in relation to schizophrenic symptoms (author's transl)].", "Very high dose fluphenazine decanoate: a controlled trial in chronic schizophrenia.", "Low-dose neuroleptic treatment of outpatient schizophrenics. I. Preliminary results for relapse rates.", "Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study.", "[Comparison of the effects of pipothiazine palmitate and fluphenazine decanoate. Results of a multicenter double-blind trial].", "The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics.", "Dose of fluphenazine, familial expressed emotion, and outcome in schizophrenia. Results of a two-year controlled study.", "Once weekly pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia.", "A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia.", "A comparative study of two long acting phenothiazine preparations, fluphenazine-enanthate and fluphenazine-decanoate.", "A controlled comparative study of fluphenazine and fluphenazine enanthate in acute and chronic psychotic patients.", "Fluphenazine enanthate and fluphenazine decanoate: a comparison of their duration of action and motor side effects." ]

[ "nan", "After a brief inpatient hospitalization, 104 acute, young schizophrenics, stratified by premorbid adjustment, were randomly assigned to one of four aftercare conditions for a six-week controlled trial. Conditions involved one of two dose levels of fluphenazine enanthate (1 ml or 0.25 ml) and presence or absence of crisis-oriented family therapy. Relapses during the six-week period and at six-month follow-up were least in patients who received both high-dose and family therapy (0%) and greatest (48%) in the low-dose-no therapy group. Brief Psychiatric Rating Scale symptom ratings disclosed a significant family therapy effect at six weeks that was sustained at six months only for therapy patients originally receiving the high drug dose. Numerous interactions were found between premorbid adjustment status and response to the two treatment conditions.", "Fifty chronic schizophrenics were randomly assigned to a 16-week treatment either with fluspirilene or with fluphenazine decanoate. The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics. Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor, severe extrapyramidal effects and parkinsonism. More patients in the fluspirilene group (nine patients) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial. Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group. The improvement in the NOSIE-30 was much more clear in the fluspirilene group. Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene, the differences between the two groups were not statistically significant.", "nan", "nan", "To evaluate a novel approach to the prophylaxis of schizophrenic relapse characterised by administration of brief courses of neuroleptic for the earliest non-psychotic signs of relapse (prodromal symptoms).\n Two year follow up of subjects randomised, double blind, to receive either active (control group) or placebo (intermittent group) depot neuroleptic medication. Both groups received brief courses of oral neuroleptic when prodromal symptoms or relapse occurred.\n Psychiatric outpatient department, Charing Cross Hospital, London.\n 54 Stable patients in remission who met the American Psychiatric Association's DSM-III criteria for schizophrenia on the basis of case notes.\n Survival without relapse, survival without hospitalisation, point prevalence of extrapyramidal side effects and tardive dyskinesia, structured assessment of social functioning (social adjustment scale II), and frequency of prodromal symptoms.\n Of 19 relapses recorded over two years, 10 (53%) were preceded by non-psychotic prodromal signs. Survival rates for both relapse and hospitalisation were worse with intermittent treatment than continuous treatment over the two year follow up: 92% of controls and only 54% of patients given intermittent treatment survived the two year period without hospitalisation. Prolonged or frequent relapses as well as episodes of prodromal symptoms were more frequent with intermittent treatment. Lower scores for extrapyramidal side effects were recorded in the intermittent treatment group, but periodic assessments of social functioning failed to show any social advantages from this.\n The findings are at variance with a previous report of one year follow up in this cohort and attest to the superiority of continuous depot neuroleptic prophylaxis in preventing both psychotic and neurotic or dysphoric morbidity in schizophrenia.", "We evaluated the effectiveness and the side effects of what we defined as low (5-mg) and conventional (25-mg) doses of fluphenazine decanoate administered every two weeks in a double-blind comparison. Subjects were 66 patients who fulfilled DSM-III criteria for schizophrenic disorder. Evaluation of the survival with each dose revealed no significant difference at one year, but significantly better survival was seen with the 25-mg dose (64%) than the 5-mg dose (31%) at two years. There was no significant difference in survival when the clinician was permitted to make a dosage adjustment up to 10 mg in the low-dose group and 50 mg in the higher-dose group when the patient demonstrated evidence of a symptomatic exacerbation. Patients assigned to the higher dose appeared to feel more uncomfortable during the early months of the study, as indicated by significantly higher scores on subscales of the Hopkins Symptom Checklist-90R and higher side effect scores for retardation and akathisia. Implications for clinical practice are discussed.", "In this present study 31 schizophrenic patients were treated for six months for relapse prevention under double-blind conditions with either haloperidol decanoate (22) or fluphenazine decanoate (9). In respect of the prophylactic action, both depot neuroleptics proved to be equal during the comparatively short period of observation. In both groups a psychotic relapse occurred that could not be managed by increasing the depot dosage. No side-effects worth mentioning appeared in either group of patients; patients under haloperidol decanoate, however, only required half the quantity of anti-parkinson medication as compared with patients treated with fluphenazine decanoate, and also displayed extrapyramidal motor symptoms (EPMS) to a lesser degree. Patients received a mean monthly injection of 80 mg of Haloperidol, reaching steady-state serum levels of about 3 ng/ml in the third injection interval. Fluphenazine serum levels known so far for seven patients amount to 0.8 ng/ml after fluphenazine injections of 21 mg every 14 days.", "The relative costs and benefits of low- and conventional-dose neuroleptic maintenance therapy were evaluated in a double-blind comparison of 5 and 25 mg of fluphenazine decanoate administered every two weeks. Subjects were 50 patients fulfilling DSM-III criteria for schizophrenic disorder who had been successfully maintained with 25 mg or less of fluphenazine decanoate. A one-year survival analysis disclosed that there were no statistically significant differences between the two doses insofar as preventing relapse. Patients receiving the higher dose appeared to feel more uncomfortable, as indicated by higher scores on subscales of the Hopkins Symptom Checklist-90. In addition, patients receiving the higher dose had higher side-effect scores. These findings suggest that a substantial proportion of patients who are presently maintained with 25 mg or less of fluphenazine decanoate every two weeks will do just as well with as little as 5 mg.", "nan", "A one year double-blind trial of haloperidol decanoate and fluphenazine decanoate was conducted in nineteen out-patients who had previously received at least one year's treatment with fluphenazine decanoate and were already overweight, as judged by a Body Mass Index of 25+. Although the difference was not statistically significant, patients treated with haloperidol decanoate showed a trend to less weight gain than patients who continued on fluphenazine decanoate, even though the haloperidol to fluphenazine dose ratio was 4:1. No statistically significant changes in mental state were observed and the incidence of extrapyramidal side-effects in the two treatment groups was similar.", "nan", "A group of patients, initially 67 individuals, with chronic schizophrenia were studied on repeated occasions during 1 year and followed up after 3 years. The patients were given depot neuroleptics, either fluphenazine decanoate or pipotiazine palmitate, at intervals of 1 month. The symptom scores from three rating scales were subjected to factor analysis. Four factors were found to explain the variance satisfactorily: one comprising psychopathological symptoms specific for schizophrenia, one relating to contact disturbances, one psychomotor activity and one representing neurotic symptoms. Analysis of these factors revealed certain differences between the treatment groups over time and demonstrated the effect of combination of psychotherapy and neuroleptic drugs in a subgroup of patients. This type of analysis of treatment results might contribute to improving our knowledge of rehabilitation of schizophrenic patients and help us to draw up giudelines for selection of suitable measures.", "Adverse effects of neuroleptic medication have led to the attempt to develop alternative strategies for the treatment of schizophrenia, but it is generally conceded that these strategies may have their own negative outcomes in the form of symptom exacerbation, reduced social performance and worsened family interactions. This paper examines the effect of one such strategy, low doses of medication, on the social adjustment of and family response to chronic schizophrenic outpatients. Patients who were randomly assigned to either a low-dose or standard-dose condition were rated by their families on various aspects of social adjustment. Despite a considerably higher relapse rate in the low-dose condition, families reported patients in the low-dose condition to be no poorer in their social adjustment than standard-dose patients. In addition, families of low-dose patients were more satisfied with their patients' overall level of adjustment and were no more rejecting at endpoint than families of standard-dose patients. Low-dose patients were viewed even more favorably when patients who relapsed were excluded from the analysis. Negative family attitudes, particularly rejection, measured at study entry, were found to predict time to relapse in the low-dose group. Implications for treatment and family intervention are discussed.", "nan", "nan", "This paper reports a randomized, controlled, partially-blinded, flexible dose, parallel group, comparative study of the efficacy and tolerance of pipothiazine palmitate and fluphenazine decanoate in patients in remission from Schizophrenia over a 28 week period. The results show that pipothiazine palmitate is at least as efficacious and well-tolerated as fluphenazine decanoate in preventing relapses from maintained Schizophrenia.", "Forty-five patients were entered into a 24-week double-blind trial of clopenthixol decanoate and fluphenazine decanoate. The 24-week double-blind period was preceded by a 12-week open period. Of the 45 patients entered, 6 failed to attend the second interview and 1 left the country before the final assessment. Doses administered were in the range 100 mg 4-weekly to 400 mg 2-weekly for clopenthixol decanoate and 12.5 mg 4-weekly to 37.5 mg 3-weekly for fluphenazine decanoate. Both depot neuroleptics appeared to have an equivalent duration of action, with 200 mg clopenthixol decanoate approximately equivalent to 25 mg fluphenazine decanoate. Patients' mental state was assessed on the Brief Psychiatric Rating Scale, Clinical Global Impression, Krawiecka, Goldberg and Vaughan Rating Scale, and unwanted effects were recorded on a checklist. No differences were detected between the two drugs with regard to therapeutic activity or side-effects. It is concluded that clopenthixol decanoate is as effective and as well-tolerated a depot neuroleptic as fluphenazine decanoate.", "The ability of long-acting fluphenazine decanoate and oral fluphenazine hydrochloride to forestall relapse among newly discharge schizophrenic patients is examined in the context of high and low degrees of social therapy (ST). A total of 105 patients were randomly assigned to the various treatments and maintained under controlled conditions for two years or until relapse. Relapse rates for all treatments remained traditionally high. Relpase rates for long-acting fluphenazine decanoate and oral fluphenazine hydrochloride are nearly identical in the first year, indicating that drug noncompliance does not adequately explain early schizophrenic relapse. However, patients who received long-acting fluphenazine decanoate and ST have a reduced risk of relapse over time. Relapsers who received long-acting fluphenazine decanoate appeared more affectively disturbed than other relapsers, yet both groups were diagnostically and symptomatically equivalent prior to treatment. Personal discomfort and intrafamilial stress are important predictors.", "The clinical and social effects of flupenthixol decanoate and fluphenazine decanoate were compared in the maintenance treatment of a population of chronic schizophrenic out-patients over a period of 9 months. The results failed to show significant difference between the treatments, and in particular, reports suggesting specific advantages for flupenthixol decanoate in alleviating the negative symptoms of apathy, anergia and depression in chronic schizophrenics were not confirmed. It seems that chronic schizophrenic patients who are well established on one depot preparation are unlikely to be benefited by being changed to the alternative.", "In a double-blind placebo substitution study, 27 chronic schizophrenic patients successfully treated for more than 2 years with fluphenazine decanoate were withdrawn from the drug. These patients showed a significantly higher relapse rate than the matched control group of 26 patients who continued to receive fluphenazine (56% versus 19%, p less than .001). This high rate of relapse is viewed as indicating the need for continued medication in most chronic schizophrenic patients.", "Seven outpatients already receiving neuroleptic drugs by depot intramuscular injections were treated in two consecutive 3-week periods with 25 mg fluphenazine doses as enanthate and decanoate esters in a double-blind crossover study. They were assessed for incidence of akinesia, involuntary movement, autonomic disturbances and drowsiness, using a rating scale, and their blood pressures and pulse rates were recorded. Blood was collected for plasma fluphenazine and plasma prolactin assay. Additionally, a handwriting test was applied. A higher incidence of unwanted drug effects occurred when plasma fluphenazine concentrations were maximal, but this was not so with prolactin concentrations. No significant blood pressure changes occurred. Small increases in pulse rate and decreases in handwriting length occurred, but these changes were not associated with high fluphenazine levels.", "nan", "Sixty patients meeting the criteria established for schizophrenia who attained a clinical plateau following hospital discharge were randomized to receive for one year either penfluridol, 20 to 160 mg orally once each week, or fluphenazine decanoate, 0.5 to 4 ml every two weeks. The relapse rate for both treatments was low and equal. The rate of recurrence of psychosis for patients receiving penfluridol was 7% and for those receiving fluphenazine decanoate 10%. A retrospective comparison of the penfluridol group was made to a similar group of patients assigned to placebo in an earlier study. Placebo-treated patients had a relapse rate of 68%. Penfluridol patients had statistically fewer psychotic relapses. Questions about the possible carcinogenicity of penfluridol in animals will have to be resolved before it can be widely used. This study demonstrates the feasibility of using an oral, long-acting antipsychotic agent. It would be a useful psychopharmacologic addition in the treatment of outpatient schizophrenics.", "Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment.\n Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years.\n Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments.\n These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.", "nan", "nan", "nan", "39 chronic schizophrenic out-patients were given either fluphenazine decanoate or enanthate for a 1-year double-blind trial. Doses of 25 mg were given for the first 6 months and 37.5 mg for the last 6 months. For both agents the intervals between treatments lengthened significantly over the course of the trial. Fluphenazine decanoate showed a non-significant trend for a longer duration of action coupled with a significantly lower incidence of extrapyramidal side effects.", "Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications.", "Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate).", "In a double-blind study of 38 chronic schizophrenic in-patients, haloperidol decanoate was compared with fluphenazine decanoate as maintenance therapy over 60 weeks. Both drugs were given by injection at 4-week intervals. Haloperidol and fluphenazine were assumed to be equipotent; the mean starting dose of the former was 127 mg and of the latter 106 mg. The number of withdrawals over 60 weeks was similar in both groups but relapses, strictly defined, were significantly more frequent in the haloperidol group. When patients were switched to haloperidol, Parkinsonism diminished more quickly than in the fluphenazine group, but after 60 weeks there was no difference in severity in the two drug groups. The higher relapse rate and the quicker reduction in Parkinsonism in the haloperidol group might be due to a misjudgement in equivalent doses of the two drugs. Plasma haloperidol steady state levels were reached in most patients by 8-12 weeks. Plasma neuroleptic and prolactin levels, week-by-week systemic drug availability and Parkinsonism showed less variation between injections with haloperidol than with fluphenazine.", "A 1 year double-blind trial of bromperidol decanoate and fluphenazine decanoate was conducted in the maintenance treatment of 47 outpatients with schizophrenia. Six patients relapsed on bromperidol decanoate and none on fluphenazine decanoate, a difference which is statistically significant. No significant differences in positive and negative symptoms, nor depression measures were found between treatment groups when comparisons were made for change in score from entry to last visit. However, patients on fluphenazine decanoate achieved significantly better changes on social disability (Morningside scale) compared to those on bromperidol decanoate. The incidence of extrapyramidal side-effects was similar in both groups, and no statistically significant differences emerged in body weight change between treatments.", "The treatment of schizophrenic patients with high-dosed neuroleptics is discussed. The drug-response difference between a low dose and a high dose of Fluphenazine-Decanoate was investigated in 40 chronic schizophrenic patients. All patients were resistant to standard doses of neuroleptics and were therefore treated with higher doses. All patients entering the study were treated for at least three months with high doses of Fluphenazine-Decanoate, i.e. 100 mg or more within three weeks. From this pool of 40 patients two groups were created at random for the doubleblind study: In one group the high dose was continued (average dose 225 mg/in 14 days), in the other group Fluphenazine-Decanoate was reduced to a standard-dose of 25 mg in 14 days. During the 24 weeks of investigation the somatic and psychopathological state of the patient was evaluated by means of the AMP-System. Furthermore the self-rating scale EWL-K was used. After 24 weeks the patients of the high-dosed group were more often rated as unchanged, while the patients in the standard-dosed group were evaluated significantly more often as better or worse. Average condition-differences between the both groups could not be found in a covariance-analysis. A factorial covariance-analysis showed that differences in the initial hostility-syndrome and catatonic-syndrome scores are predictors for a syndrom-relevant differential dosage per group. Patients with low hostility- and low catatonic-syndrome-scores improved after reduction of the doses in the apathic, the halluzinatoric-desintegrative and the neurological syndrome, whereas patients with high initial hostility- and catatonic-syndrome-scores became psychopathologically worse after dosage reduction. Finally the possibilities of generalizing from the results obtained to the relevance of high and standard neuropletic therapy are discussed.", "In a double-blind trial of six months' duration, a very high dose (VHD) regimen of fluphenazine decanoate (250 mg weekly) was compared with a standard dose (SD) regimen (12.5 mg weekly) in 50 chronic schizophrenic patients. The rating scales used included the Brief Psychiatric Rating Scale and the Wing Ward Behavior Scale. Both treatment groups improved during the trial, but there was no significant difference between them. The VHD regimen, however, exerted better control of the psychosis in that it had fewer patient dropouts and fewer \"additional treatments\" prescribed. Some of the patients receiving standard doses were probably not receiving adequate antipsychotic drug dosage. No predictors of clinical response could be defined. Extrapyramidal side effects were not significantly higher in the VHD group.", "In an attempt to begin to establish minimum effective dosage requirements for the maintenance treatment of schizophrenia, we undertook a double-blind comparison of low-dose fluphenazine decanoate (1.25 to 5.0 mg/2 wk) with the standard-dose regimen (12.5 to 50.0 mg/2 wk) in outpatient schizophrenics. For the first 126 patients studied, cumulative relapse rates at one year for the low dose were 56% and for the standard dose 7%, a significant difference. Despite the fact that very little dyskinetic symptomatology developed in the sample as a whole, the low-dose treatment appeared to have a significant advantage in producing fewer early signs of tardive dyskinesia. Severity of relapse and total cumulative dosage were also considered.", "The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance.", "Fluphenazine decanoate and pipothiazine palmitate were compared concerning their effect and side-effects. 61 schizophrenic patients were treated up to 6 months in a multicenter double-blind trial. Assessments were made on day 0 and after 5, 10, 17 and 22 weeks of treatment using the AMP system. Pipothiazine palmitate was injected every 4th week and fluphenazine decanoate every 3rd week. The most often applied dosage was 100 mg pipothiazine palmitate and 25 or 37.5 mg fluphenazine decanoate. Data analysis of the AMP system at the symptom level showed the better antipsychotic effect of pipothiazine palmitate. A comparison between the two groups by means of analysis of covariance at the syndrome level showed no statistical significant differences between the effects of fluphenazine decanoate and pipothiazine palmitate.", "Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning.", "Issues regarding the side effects of antipsychotic medication and the possible contribution of the environment to dose requirements led to a two-year controlled dosage study of maintenance antipsychotic medication and familial environment among recently discharged schizophrenic patients. Seventy stable patients, living in high- or low-expressed emotion (EE) households, were randomized, double blind, to receive a standard dose of fluphenazine decanoate (average, 25 mg every two weeks) or a minimal dose representing 20% of the dose prescribed (average, 3.8 mg every two weeks). No differences in relapse were observed among dose, EE, or dose and EE. Patients in the minimal dose/high-EE condition experienced more minor but aborted episodes in year 2. Side effects were fewer on the minimal dose after one year, and low-EE patients were better adjusted than high-EE patients. Over time, minimal-dose recipients were significantly more improved in their instrumental and interpersonal role performance than were standard-dose recipients.", "In a double blind trial, 28 male chronic schizophrenic in-patients received either pimozide, given once weekly, or fluphenazine decanoate, given mostly once fortnightly. There was no difference in relapse rates over nine months. However, three-quarters of the patients on pimozide who completed the trial developed at least mild tardive dyskinesia. All patients on pimozide lost weight, the average loss being 5.4 kg (12 lbs). Plasma pimozide levels suggested satisfactory drug compliance. Plasma prolactin levels confirmed that in the pimozide group there was fluctuating dopamine receptor antagonism, while in the fluphenazine group average plasma prolactin levels throughout most of the interval between injections were at the upper limit of normal.", "A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one.", "nan", "nan", "nan" ]

[ "9787684", "10103297", "2963059", "2934747", "9018183", "3318574", "9761804", "9555617", "2144115", "2931507", "7699549" ]

[ "Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma.", "Ipratropium bromide added to asthma treatment in the pediatric emergency department.", "Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children.", "Ipratropium and fenoterol in the treatment of acute asthma.", "Efficacy of nebulized ipratropium in severely asthmatic children.", "Comparison of inhaled metaproterenol, inhaled atropine sulfate, and their combination in treatment of children with acute asthma.", "Effect of nebulized ipratropium on the hospitalization rates of children with asthma.", "Is it useful to add an anticholinergic treatment to beta 2-adrenergic medication in acute asthma attack?", "Comparison of inhaled terbutaline and inhaled terbutaline plus ipratropium bromide in acute asthmatic children.", "Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma.", "Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma." ]

[ "To compare the effectiveness and safety of alternative nebulized drug protocols in children with mild or moderate asthma exacerbations.\n We conducted a blinded, randomized, controlled trial with a 2 x 2 factorial design. Two interventions, nebulized salbutamol in frequent low doses (0.075 mg/kg every 30 minutes) and the addition of ipratropium bromide (250 micrograms), were compared with salbutamol in hourly high doses (0.15 mg/kg every 60 minutes) in children with mild or moderate acute asthma. The primary end point was the improvement in respiratory resistance. Secondary end points included oxygen saturation, corticosteroid use, patient disposition, and relapse status.\n A total of 298 participants aged 3 to 17 years were studied, and 15% were admitted to the hospital; 14% of the children had relapses. No increased bronchodilation was associated with frequent low doses versus hourly high doses of salbutamol (RR = 0.9 [95% confidence interval 0.7, 1.3]) or the addition of ipratropium bromide versus placebo (RR = 1.0 [0.8, 1.3]). No group differences were observed in secondary end points. Salbutamol in frequent low doses was associated with increased vomiting (RR = 2.5 [1.1, 6.0]).\n Our results do not support the use of frequent low doses of nebulized salbutamol or the addition of ipratropium bromide compared with hourly high doses of salbutamol in children with mild or moderate asthma.", "To determine if the addition of ipratropium bromide to the emergency department (ED) treatment of childhood asthma reduces time to discharge, number of nebulizer treatments before discharge, and the rate of hospitalization.\n Patients >12 months of age were eligible if they were to be treated according to a standardized ED protocol for acute asthma with nebulized albuterol (2.5 mg/dose if weight <30 kg, otherwise 5 mg/dose) and oral prednisone or prednisolone (2 mg/kg up to 80 mg). Subjects were randomized to receive either ipratropium (250 microg/dose) or normal saline (1 mL/dose) with each of the first three nebulized albuterol doses. Further treatment after the first hour was determined by physicians blinded to subject group assignment. Records were reviewed to determine the length of time to discharge home from the ED, number of doses of albuterol given before discharge, and the number of patients admitted to the hospital.\n Four hundred twenty-seven patients were randomized to ipratropium or control groups; these groups were similar in all baseline measures. Among patients discharged from the ED, ipratropium group subjects had 13% shorter treatment time (mean, 185 minutes, vs control, 213 minutes) and fewer total albuterol doses (median, three, vs control, four). Admission rates did not differ significantly (18%, vs control, 22%).\n The addition of three doses of ipratropium to an ED treatment protocol for acute asthma was associated with reductions in duration and amount of treatment before discharge.", "A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma. A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide. Twenty-five children ranging in age from 5 to 15 years were enrolled in the study. Children with FEV1 less than or equal to 55% predicted were eligible to participate in the study. Subjects were randomized in a double-blind fashion into one of two treatment groups. Both groups received an initial dose of salbutamol by nebulizer of 150 micrograms/kg (0.03 cc/kg), followed by six consecutive doses of 50 micrograms/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 micrograms (1.0 ml) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation, and at 40 and 80 minutes, whereas the remaining subjects received a placebo with salbutamol at those times. Formal one-way statistical ANOVA with change in percent predicted FEV1 as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period. There was no significant difference in side effects reported in the two groups. Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group.", "A double-blind, randomized trial was carried out in 48 children to assess the effects of inhaled ipratropium bromide, fenoterol or a combination of both drugs in treating their moderately severe acute asthma. Doses were adjusted according to the age of the patients and administered by nebulizer. Measurements of pulse rate and respiratory rate and assessment of the severity of symptoms were made at fixed intervals during the first 2 hours on treatment. Repeat nebulizations were given, if necessary, at 2-hourly intervals. The results suggested that fenoterol provided the most adequate treatment and there was no evidence to indicate that the addition of ipratropium produced any improved benefit.", "To determine the effect of adding the nebulized anticholinergic drug ipratropium bromide to standard therapy compared with standard therapy alone for acute severe asthma (peak expiratory flow rate [PEFR] < 50% of predicted) in children presenting to the emergency department.\n Ninety children aged 6 to 18 years were randomly assigned to two groups in a prospective, double-blind, placebo-controlled study performed in the ED of an urban children's hospital. All children received nebulized albuterol solution (.15 mg/kg) every 30 minutes, and all received oral steroids with the second dose of albuterol. Children in group 1 received ipratropium bromide (500 micrograms/dose) with the first and third dose of albuterol those in group 2 received saline placebo instead of ipratropium. Pulmonary functions (PEFR and 1-second forced expiratory volume [FEV1]) and physiologic measurements were assessed every 30 minutes up to 120 minutes. By chance, the baseline values for percent of predicted PEFR and FEV1 differed between the two groups. Therefore a multivariate model accounting for both time and baseline effects was used to compare the response between groups.\n On average, and adjusting for baseline measures, children in the ipratropium group had a significantly greater improvement in percent of predicted PEFR than did children in the placebo group at 60 minutes (P = .02), 90 minutes (P = .002), and 120 minutes (P < .0001). The improvement in percent predicted FEV1 was significantly greater for children in the ipratropium group only at 120 minutes (P = .013). Nine children (20%) from the ipratropium group and 14 (31.1%) from the control group were admitted (P = .33, chi 2). There were no significant adverse effects attributable to the ipratropium, and there was no relation between ipratropium use and changes in pulse, respiratory rate, blood pressure, or oxygen saturation.\n We detected significant improvement in pulmonary function studies over 120 minutes in children with severe asthma who were given nebulized ipratropium combined with albuterol and oral steroids, compared with children who received the standard therapy. Further study is needed to determine whether early use of ipratropium decreases the need for hospitalization.", "The separate and combined effects of inhaled metaproterenol and atropine sulfate were evaluated in the treatment of 44 episodes of acute asthma occurring in 35 children ranging in age from 13 months to 13 years. Peak expiratory flow rate and pulmonary index were measured before and after each of up to three inhalation treatments. Significant improvement in peak flow rate (P less than .04) was noted after the second inhalation of metaproterenol both with and without the combination of atropine sulfate compared with the effects of atropine alone. Patients treated with metaproterenol and metaproterenol combined with atropine also experienced fewer therapeutic failures (2/15 and 2/16, respectively) compared with those treated with atropine (6/13, P less than .02). Pulmonary index scores did not differ among the treatment groups. Inhaled metaproterenol appears to be more effective than inhaled atropine sulfate in the treatment of children with acute asthma. The addition of inhaled atropine sulfate appears to offer no advantage over treatment with inhaled metaproterenol alone.", "Anticholinergic medications such as ipratropium improve the pulmonary function of patients with acute exacerbations of asthma, but their effect on hospitalization rates is uncertain.\n We conducted a randomized, double-blind, placebo-controlled study of 434 children (2 to 18 years old) who had acute exacerbations of moderate or severe asthma treated in the emergency department. All the children received a nebulized solution of albuterol (2.5 or 5 mg per dose, depending on body weight) every 20 minutes for three doses and then as needed. A corticosteroid (2 mg of prednisone or prednisolone per kilogram of body weight) was given orally with the second dose of albuterol. Children in the treatment group received 500 microg (2.5 ml) of ipratropium bromide with the second and third doses of albuterol; children in the control group received 2.5 ml of normal saline at these times.\n Overall, the rate of hospitalization was lower in the ipratropium group (59 of 215 children [27.4 percent]) than in the control group (80 of 219 [36.5 percent], P=0.05). For patients with moderate asthma (indicated by a peak expiratory flow rate of 50 to 70 percent of the predicted value or an asthma score of 8 to 11 on a 15-point scale), hospitalization rates were similar in the two groups (ipratropium: 8 of 79 children [10.1 percent]; control: 9 of 84 [10.7 percent]). For patients with severe asthma (defined as a peak expiratory flow rate of <50 percent of the predicted value or an asthma score of 12 to 15), the addition of ipratropium significantly reduced the need for hospitalization (51 of 136 children [37.5 percent], as compared with 71 of 135 [52.6 percent] in the control group; P=0.02).\n Among children with a severe exacerbation of asthma, the addition of ipratropium bromide to albuterol and corticosteroid therapy significantly decreases the hospitalization rate.", "The aim of our study was to determine whether the combination of an anticholinergic treatment with a beta 2-adrenergic medication is a more effective treatment for acute asthma attack than the two treatments individually. The association of salbutamol-ipratropium was compared to treatment with salbutamol and ipratropium alone. It was a prospective double-blind study in children with acute asthma attack, participating as outpatients. Their clinical history and characteristics of bronchial obstruction were recorded on a standard form. Afterwards, they were included in one of the three following study groups: group one, 100 micrograms/inh salbutamol; group two, 20 micrograms/inh ipratropium; group three, 100 micrograms/inh of salbutamol plus 20 micrograms/inh ipratropium. There were 40 patients in each group, with Tal score +/- 5 and PEF < 80% of the predicted value. They were evaluated at the beginning (0 min), and at 15, 30, 45, 60, 80, 100 and 120 min. Each patient was treated with two inhalations of the study medication and was then evaluated for variations in Tal score. The mean age was 7.3 years; Tal score was 5.6, 5.6 and 6.0 at 0 min (p > 0.05). Decrease in Tal score after 15 min meant p < 0.01 for salbutamol-ipratropium and salbutamol vs. ipratropium. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol, and at 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol. PEF at 0 min was 70.9%, 71.3% and 68.6% (p > 0.05) increasing after 15 min. At 30 min p < 0.05 for salbutamol-ipratropium vs. salbutamol, and p < 0.01 vs. ipratropium. At 45 min p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. A total 4.7 doses of salbutamol were needed to improve the asthma attack, 5.3 of ipratropium and 3.7 of salbutamol-ipratropium, with p < 0.01 for salbutamol-ipratropium vs. salbutamol and ipratropium. We conclude that the combination of salbutamol and ipratropium is more effective than each medication alone in treating acute asthma attacks in pediatric patients.", "Twenty asthmatic children, aged 4 to 15 years, consisting of 14 boys and 6 girls, were studied during acute episodes of asthmatic attacks. A group of 10 children each received either inhaled terbutaline 0.5 mg or inhaled terbutaline 0.5 mg followed by ipratropium bromide 0.04 mg 15 minutes later through a 750-ml volumetric spacer. Significant increases in FEV1 over the baseline were observed from 2 minutes to 2 hours and from 2 minutes to 6 hours following the first and second regimen respectively. A slightly greater increase and longer duration in FEV1 were observed in the combined drug treatment and very slight decreases in systolic and diastolic blood pressure below the base-line were observed. Neither regimen showed any serious adverse effect on the heart rate and respiratory rate.", "nan", "The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma.\n One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in 1 second (FEV1), < 50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 micrograms/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes.\n The groups were comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differences between groups were larger in those children with a baseline FEV1 < or = 30% of the predicted value: FEV1 increased from 24.5% to 50.9% in group 1, from 25.0% to 39.8% in group 2, and from 25.9% to 36.5% in group 3 (p = 0.0001). In group 1, 38% of the patients were hospitalized after the study, 44% in group 2, and 46% in group 3 (p value not significant). However, in patients with FEV1 < or = 30%, the hospitalization rates were 27% in group 1, 56% in group 2, and 83% in group 3 (p = 0.027). There were no toxic effects attributable to ipratropium.\n The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone; its use in patients with very severe asthma may reduce hospitalizations." ]

[ "2036277", "7665721", "18991469" ]

[ "Double-blind placebo-controlled comparison of the analgesic effects of single doses of lornoxicam and aspirin in patients with postoperative dental pain.", "A randomized, double-blind, placebo-controlled, dose-response study of the analgesic effect of lornoxicam after surgical removal of mandibular third molars.", "Analgesic efficacy of quick-release versus standard lornoxicam for pain after third molar surgery: a randomized, double-blind, placebo-controlled, single-dose trial." ]

[ "The pain experienced after third molar surgery was used as a model to evaluate the analgesic efficacy of a new non-steroidal anti-inflammatory drug, lornoxicam, in a Phase II study. One hundred and fifty fit, young adults participated in this randomised, single dose, double-blind, parallel group clinical study. Three doses of lornoxicam (2 mg, 4 mg, and 8 mg) were compared with aspirin 650 mg and placebo. Patients suffering from moderate to severe pain following surgery were monitored for up to 8 hours. All indices of efficacy showed similar results, all active treatments being associated with highly significant (P less than 0.0001) reductions in pain during the study period. Lornoxicam 8 mg demonstrated significant analgesic efficacy as compared with placebo. The two lower doses of lornoxicam and aspirin all showed apparent degrees of efficacy intermediate between that of placebo and lornoxicam 8 mg, although the trial proved to have inadequate power to show significant differences between these three treatments. Lornoxicam was very well tolerated at all three doses studied, with no adverse events definitely attributable to its administration.", "The aim of the present study was to investigate the dose-effect relationship of single doses of 4 to 32 mg of lornoxicam (LNX), a new nonsteroidal antiinflammatory drug belonging to the oxicam group, compared with placebo and 10 mg ketorolac (KET) in the treatment of pain after oral surgery. Also, it was the aim of the study to evaluate the relationship between adverse events and different doses of LNX. After the surgical removal of a mandibular third molar, test medication was taken when the patients experienced at least moderate pain. After medication, pain relief, pain intensity, and any discomfort from the medication were noted in a questionnaire. Paracetamol was used as rescue medication. A total of 278 patients completed the study according to the protocol. The primary efficacy parameter was total pain relief after 6 hours, and all active treatments showed significantly better effect than placebo, with LNX 16 and 32 mg being significantly superior to LNX 4 mg. All other efficacy parameters showed the same dose-effect relationship. A total of 37 adverse events were reported evenly distributed in the 6 treatment groups; only 3 of these were considered severe, and all disappeared without treatment. In conclusion, the study showed a dose-effect relationship of LNX without a rise in adverse events. The effect of 10 mg KET seemed to be at the level of 8 to 16 mg LNX.", "The aim of this study was to evaluate the analgesic efficacy and time to onset of effect of the lornoxicam quick-release (LNX-QR) tablet compared with the standard-release tablet (LNX-ST).\n In this randomized, double-blind, single-dose trial, 200 patients with moderate pain after surgical removal of an impacted third molar were randomized to treatment with an LNX-QR 8 mg tablet (80 patients), an LNX-ST 8 mg tablet (80 patients) or placebo (40 patients). Pain intensity (PI) and pain relief (PAR) were assessed (numerical and verbal rating scales) for 6 hours, and time to onset of PAR was recorded. The cumulated sum of PI differences (SPID) and PAR (TOTPAR) were calculated. Tolerability was evaluated by occurrence of adverse events.\n Kaplan-Meier analysis of time to onset of analgesic efficacy demonstrated a significantly faster onset with LNX-QR than placebo or LNX-ST (p < 0.0001). Median time of onset was 32 minutes (range 29-37) for LNX-QR and 46 minutes (range 37-59) for LNX-ST. The analgesic efficacy of LNX-QR and LNX-ST were superior to that of placebo, whereas paired comparisons of TOTPAR and SPID showed LNX-QR to be superior to LNX-ST (p < 0.05).\n LNX-QR provided a faster onset and superior analgesic effect against pain following third molar surgery than LNX-ST." ]

[ "7573015", "8840939", "2266671", "10084465", "11208997", "2919849", "12865102", "9487416", "9773794", "8129434", "11868861", "12608556" ]

[ "Effect of albuterol treatment on subsequent dialytic potassium removal.", "Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol.", "Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients.", "Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe?", "Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal.", "Nebulized albuterol for acute hyperkalemia in patients on hemodialysis.", "Levalbuterol is as effective as racemic albuterol in lowering serum potassium.", "Treatment of hyperkalaemia by altering the transcellular gradient in patients with renal failure: effect of various therapeutic approaches.", "Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease.", "Treatment of hyperkalaemia using intravenous and nebulised salbutamol.", "Comparison of aminophylline and insulin-dextrose infusions in acute therapy of hyperkalemia in end-stage renal disease patients.", "Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal." ]

[ "End-stage renal disease patients presenting with severe hyperkalemia are frequently treated with albuterol to lower their plasma potassium acutely, until emergent hemodialysis can be initiated. Such treatment stimulates potassium shifts from the extracellular to the intracellular fluid compartments. The resulting reduction of potassium concentration gradient between the blood and dialysate may potentially attenuate the efficacy of potassium removal during the ensuing hemodialysis treatment. To evaluate the effect of prior albuterol treatment on dialytic potassium removal, seven chronic hemodialysis patients were studied prospectively on two separate occasions. In one study the patients received 20 mg nebulized albuterol 30 minutes before dialysis; in the control study, albuterol treatment was omitted. Plasma potassium decreased 30 minutes after albuterol treatment (-0.84 +/- 0.06 mmol/L; P < 0.001) and remained unchanged in the corresponding period of the control experiment. Plasma potassium decreased during dialysis in both experimental protocols, but was significantly lower throughout dialysis in the albuterol study, as compared with the control study. Cumulative dialytic potassium removal was significantly lower following albuterol pretreatment compared with the control experiment (29.0 +/- 5.7 mmol v 49.6 +/- 7.0 mmol; P < 0.001). These observations suggest that acute albuterol therapy in patients with end-stage renal disease may substantially decrease potassium removal in the ensuing hemodialysis session. This may lead to rebound hyperkalemia several hours after the dialysis treatment.", "Acute treatment of hyperkalemia in patients with end-stage renal disease requires temporizing measures to shift potassium rapidly from the extracellular to the intracellular fluid compartments until hemodialysis can be initiated. Whereas insulin and albuterol are effective in lowering plasma potassium acutely, bicarbonate by itself is not. Bicarbonate administration may, however, potentiate the effects of insulin and albuterol on plasma potassium. Using a prospective cross-over design, we investigated the acute effects of (1) isotonic bicarbonate, (2) isotonic saline, (3) insulin + bicarbonate, (4) insulin + saline, (5) albuterol + bicarbonate, and (6) albuterol + saline on plasma potassium as well as blood bicarbonate and pH in nondiabetic hemodialysis patients. After obtaining a baseline blood sample, the subjects received one of the six treatment protocols, with plasma potassium measured every 15 minutes over 1 hour. Neither isotonic bicarbonate nor isotonic saline decreased plasma potassium significantly (-0.03 +/- 0.06 mmol/L v -0.01 +/- 0.10 mmol/L at 60 minutes; P = 0.60). Intravenous insulin decreased plasma potassium by a similar degree when given in conjunction with bicarbonate or saline (-0.81 +/- 0.05 mmol/L v -0.85 +/- 0.06 mmol/L at 60 minutes; P = 0.65). Likewise, nebulized albuterol decreased plasma potassium by a similar degree when given with bicarbonate or saline (-0.71 +/- 0.16 mmol/L v -0.53 +/- 0.15 mmol/L at 60 minutes; P = 0.18). The three protocols that included bicarbonate administration resulted in significant increases in blood bicarbonate (P < 0.005) and pH (P < 0.01), whereas the three protocols that included saline did not affect blood bicarbonate or pH. These observations suggest that bicarbonate administration does not potentiate the potassium-lowering effects of insulin or albuterol in hemodialysis patients.", "We evaluated in maintenance hemodialysis patients the potassium lowering effects of intravenous insulin with glucose, nebulized albuterol, and a regimen combining both modalities. There was a similar decrease in plasma potassium following either insulin with glucose (0.65 +/- 0.09 mmol/liter) or albuterol (0.66 +/- 0.12 mmol/liter), and a substantially greater fall with the combined regimen (1.21 +/- 0.19 mmol/liter, P less than 0.02 vs. either drug alone). Baseline plasma glucose concentrations were similar (about 4.8 mmol/liter) prior to all three treatments. Following insulin with glucose, plasma glucose increased transiently. but then fell to 2.8 +/- 0.3 mmol/liter at one hour, with concentrations below 3 mmol/liter in 9 of 12 patients. None of the patients had symptoms of hypoglycemia. Plasma glucose increased to 6.8 +/- 0.5 mmol/liter with albuterol. After the combined drug regimen plasma glucose rose transiently and was back to baseline (4.7 +/- 0.7 mmol/liter) at one hour. Treatment with insulin or albuterol produced trivial increases in heart rate, whereas the combined drug regimen was associated with a significant rise (15.1 +/- 6.0 min-1). These observations suggest that albuterol and insulin with glucose are equally efficacious in lowering plasma potassium in uremic patients, and that the hypokalemic effects of the two drugs is additive. The hypoglycemic effect of insulin is attenuated by coadministration albuterol. Combined therapy with insulin, glucose and albuterol is efficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients.", "To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia.\n A randomized, double-blind, placebo-controlled trial.\n Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized.\n Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected.\n Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia.", "The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD).\n Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined.\n 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments.\n Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD.", "To determine the efficacy and safety of nebulized albuterol in the acute treatment of hyperkalemia in patients on chronic hemodialysis.\n Prospective, double-blind, and placebo-controlled study.\n Outpatient hemodialysis clinic at a university medical center.\n Ten patients on maintenance hemodialysis who had chronic hyperkalemia.\n Patients received nebulized albuterol therapy (10 mg or 20 mg) or placebo (saline) on three separate occasions, serial measurements of plasma potassium levels, blood pressure, and pulse were then taken for a 2-hour period.\n Patients had a significant decrease in plasma potassium concentrations that was evident by 30 minutes and sustained for at least 2 hours after albuterol treatment. After the administration of 10- and 20-mg doses of albuterol, the maximal decrease in the plasma potassium levels was 0.62 +/- 0.09 and 0.98 +/- 0.14 mmol/L (SE), respectively. Nebulized saline administration did not produce a significant change in the plasma potassium concentrations. Patients did not develop symptoms or significant changes in blood pressure or heart rate with albuterol treatment.\n In the doses used, nebulized albuterol therapy resulted in a prompt and significant decrease in the plasma potassium concentrations in patients on hemodialysis, and caused no adverse cardiovascular effects. This treatment should be considered as an important adjunct for acute treatment of serious hyperkalemia in this population of patients.", "Albuterol is an effective treatment for hyperkalemia through beta-adrenergic induction of potassium (K+) uptake. Levalbuterol, the R-enantiomer of racemic albuterol, is used for the treatment of asthma and 0.63 mg of levalbuterol has the same therapeutic efficacy as 2.5 mg of albuterol but with a decreased adverse effects profile. We hypothesized that levalbuterol can reduce serum K+ levels similarly to albuterol when used in equipotent doses. In a randomized, double blind, placebo-controlled prospective study, we compared the K+-lowering effects of nebulized saline and equipotent bronchodilatory doses of albuterol (10 mg) and levalbuterol (2.5 mg) in healthy adult volunteers. Nine subjects entered each of the three study groups. Serum K+ was measured at baseline, at 30 min (immediately after treatment), at 60 min, and at 90 min. All adverse effects were recorded. The three groups had similar baseline K+ values. Immediately after nebulization, only levalbuterol showed a significant decrease in potassium level (p = 0.024). At 30 and 60 min after treatment, both albuterol and levalbuterol groups had significantly lower K+ values compared to placebo. No significant difference occurred between the albuterol and levalbuterol groups. Levalbuterol caused fewer reported adverse effects compared to albuterol.", "Ten patients with acute and 60 with chronic renal failure (both groups having hyperkalaemia), were managed at Kenyatta National Hospital in the medical wards and Renal Unit between August, 1995 and January, 1996. They were divided into seven different treatment groups, each consisting of ten patients. Treatment A glucose 25g i.v. with insulin 10 units i.v., treatment B 50 mmol of 8.4% sodium bicarbonate infusion, treatment C 0.5mg of salbutamol i.v. in 50mls 5% dextrose, treatment D was a combination of treatments A and B, treatment E was a combination of treatment B and C, treatment F was a combination of treatments A and C while treatment G was a combination of treatments A and B and C. Serum potassium was measured, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours after treatment. Plasma glucose concentration was measured before treatment was given and 1 hour after in all patients. Electrocardiography was done before treatment on all patients and repeated 30 minutes and 1 hour after treatment for the patients with hyperkalaemic changes on the initial recording. All treatment modalities had satisfactory potassium lowering effects. Of the single therapeutic approaches, treatment A and C were equieffective, but better than treatment B (P < 0.001). Amongst the two regimen combinations, treatment D and F were more efficacious than treatment E and all the single therapeutic approaches (P < 0.001). Treatment G was the most efficacious in lowering serum potassium in this study. All treatment modalities had maximum serum potassium lowering effect at 1-2 hours. A fall in plasma glucose concentration was a notable feature of treatments A and D, but significant hypoglycaemia occurred in 20% of patients receiving treatment A and in none on treatment D. The ECG changes of hyperkalaemia did not correlate with serum potassium levels. The normalisation of hyperkalaemic ECG alteration occurred within the first 30 minutes after treatment. In conclusion, combination therapies for hyperkalaemia appear to be more efficacious than single therapeutic approaches. Inclusion of salbutamol seems to protect against insulin induced hypoglycaemia. The maximum potassium lowering effect is observed 1-2 hours of administration of either agents. The potassium reducing effect remains significant compared to baseline values even after 8 hours. If dialysis cannot be instituted early enough it seems reasonable to repeat treatment every 4-6 hours to sustain the effect. Repeated administration of glucose with insulin may not be safe because of the hypoglycaemic effect. Other single and combination therapies can theoretically be repeated regularly until dialysis is initiated although this requires further clinical evaluation.", "Hyperkalemia in patients with renal failure is frequently treated with a cation exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in combination with a cathartic, but the effect of such therapy on serum potassium concentration has not been established. This study evaluates the effect of four single-dose resin-cathartic regimens and placebo on 5 different test days in six patients with chronic renal failure. Dietary intake was controlled. Fecal potassium output and serum potassium concentration were measured for 12 h. Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The addition of resin caused an increase in insoluble potassium output but a decrease in soluble potassium output; therefore, there was no significant effect of resin on total potassium output. Sorbitol plus resin caused less potassium output than phenolphthalein plus resin. On placebo therapy, the average serum potassium concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This rise was apparently abrogated by some of the regimens that included resin; this may have been due in part to extracellular volume expansion caused by absorption of sodium released from resin. Phenolphthalein regimens were associated with a slight rise in serum potassium concentrations (similar to placebo); this may have been due to extracellular volume contraction produced by high volume and sodium-rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens reduced serum potassium concentrations, compared with baseline levels. Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes.", "In 11 children (aged 5-18 years) with end stage chronic renal failure, the effect on plasma potassium of two doses of salbutamol (separated by two hours) given intravenously (4 micrograms/kg) and on a separate date, of salbutamol administered by nebuliser (2.5 mg if the child weighed below 25 kg, 5 mg if above) was observed. Within 30 minutes of the first dose, the mean plasma potassium concentration fell significantly by 0.87 and 0.61 mmol/l after intravenous and nebulised administration respectively. Sixty minutes after the second dose the plasma potassium was significantly reduced by a further 0.28 and 0.53 mmol/l respectively. There was a significant difference between the two methods of administration at 300 minutes after the first dose favouring nebulisation. No major side effects were observed. Nebulised salbutamol should be the first choice emergency treatment of hyperkalaemia.", "This study was performed to compare the efficacy of aminophylline and insulin-dextrose infusion as acute treatment modality of hyperkalemia in patients with end-stage renal disease (ESRD).\n This study was conducted on 30 ESRD patients with serum potassium > 6.0 mEq/L. These patients were divided in two groups of 15 each. Group A patients were treated with aminophylline infusion, whereas group B patients were treated with insulin-dextrose infusion. Serum potassium and other biochemical parameters such as blood sugar were measured at beginning of treatment followed by at 60 minutes, 180 minutes, and 360 minutes after treatment.\n Intervenous infusion of aminophylline lowered plasma potassium from 6.48 +/- 0.39 mEq/L to 5.92 +/- 0.40 mEq/L at 180 minutes (p < 0.001 Vs basal) and 6.05 +/- 0.53 mEq/L at 360 minutes (p < 0.01 Vs basal). Whereas, intravenous infusion of insulin-dextrose decreased plasma potassium from 6.59 +/- 0.31 mEq/L to 5.76 +/- 0.32 mEq/L (p < 0.001 Vs basal) and 5.84 +/- 0.21 mEq/L (p < 0.001 Vs basal). Thus in both groups, plasma potassium levels were significantly less than basal levels throughout the study. The decrease in plasma potassium was significantly more in group B patients (p value is < 0.001 after 60 minutes, < 0.05 after 180 minutes and < 0.05 after 360 minutes) when compared to group A patients. There was one episode of hypoglycemia (blood sugar < 60 mg%) in insulin-dextrose infusion group. No other side effects were observed throughout the study.\n Aminophylline is an effective modality for acute treatment of hyperkalemia, though it is less effective than insulin-dextrose infusion. However, more studies are required to confirm these results.", "Hyperphosphatemia and hyperkalemia are major determinants of morbidity and mortality in hemodialysis patients. Half of the dialysis population suffers from hyperphosphatemia which is now recognized as an important cardiovascular disease risk factor. It is, therefore, necessary to improve the removal of these molecules. In this study, we investigated the effect of enhancing blood flow on Kt/V for urea (Kt/Vu), potassium and phosphate removal.\n Thirteen patients were investigated in a randomized, cross-over, prospective study using 3 blood flows (Qb) of 200,250 and 300 ml/min which gave 39 standardized high-flux hemodialysis treatments. Effective blood flows were measured by ultrasonic flow meter. Quantification of delivered dialysis dose was performed by partial dialysate and ultrafiltrate collection for the determination of potassium and phosphate removal and by blood urea concentrations for determination of Kt/Vu.\n Kt/Vu rose significantly from 1.10 +/- 0.14 to 1.22 +/- 0.14 and finally to 1.39 +/- 0.16 (p = 0.0001) with increasing Qb similar to the increase in potassium removal from 53.0 +/- 2.4 to 63.4 +/- 2.6 and to 74.2 +/- 3.8 mMol (p = 0.01). Phosphate removal only improved from 28.1 +/- 1.3 to 31.4 +/- 1.5 (p = 0.050) when Qb was increased from 200 to 250 ml/min but remained unchanged at 31.2 +/- 1.5 mMol (NS compared to phosphate removal at Qb = 250 ml/min) when Qb was increased to 300 ml/min.\n Increasing delivered Kt/Vu and potassium removal with higher Qb fails to produce the same desired effect with phosphate removal during high-flux hemodialysis." ]

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[ "Efficacy of live attenuated influenza A/Scotland/74 (H3N2) virus vaccine against challenge with influenza A/Victoria/3/75 (H3N2) virus.", "Efficacy of sequential annual vaccination with inactivated influenza virus vaccine.", "A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease.", "Correlated studies of a recombinant influenza-virus vaccine. IV. Protection against naturally occurring influenza in military trainees.", "Immunogenicity of 1967 polyvalent and 1968 Hong Kong influenza vaccines.", "Is there a relationship between influenza vaccinations and risk of melanoma? A population-based case-control study.", "Field trial of live attenuated influenza A/B (\"Alice\"/R-75) vaccine.", "The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.", "Effect of live attenuated, cold recombinant (CR) influenza virus vaccines on pulmonary function in healthy and asthmatic adults.", "Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers.", "Guillain-Barré syndrome in the United States, 1979-1980 and 1980-1981. Lack of an association with influenza vaccination.", "WRL 105 strain live attenuated influenza vaccine; comparison of one and two dose schedules.", "Ocular and respiratory symptoms attributable to inactivated split influenza vaccine: evidence from a controlled trial involving adults.", "Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial.", "Influenza A virus vaccines containing purified recombinant H3 hemagglutinin are well tolerated and induce protective immune responses in healthy adults.", "An evaluation of influenza immunization: influence of route of administration and vaccine strain.", "An assessment of oil adjuvant and aqueous influenza vaccines. I. Reactions to the vaccines.", "The effectiveness of vaccination against influenza in healthy, working adults.", "Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period.", "A placebo-controlled dose-response study of the reactogenicity and immunogenicity of a cold-adapted recombinant A/Victoria/3/75 (H3N2) live influenza virus candidate vaccine in healthy volunteers.", "[Effectiveness of an influenza vaccine in a working population in Colombia].", "Reactogenicity and immunogenicity of parenteral monovalent influenza A/Victoria/3/75 (H3N2) virus vaccine in healthy adults.", "Effectiveness and cost-benefit of influenza vaccination of healthy working adults: A randomized controlled trial.", "Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976--1977.", "Trivalent attenuated cold-adapted influenza virus vaccine: reduced viral shedding and serum antibody responses in susceptible adults.", "Safety and immunogenicity of a Proteosome -trivalent inactivated influenza vaccine, given nasally to healthy adults.", "Studies in man with a cold-recombinant live influenza B virus vaccine.", "Anthrax vaccination and risk of optic neuritis in the United States military, 1998-2003.", "The effect of vaccine on a closed epidemic of Hong Kong influenza.", "Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza vaccines administered intranasally to healthy adults.", "[Results of a study of the effectiveness of simultaneous immunization against influenza with live and inactivated vaccines (1980-1983)].", "Efficacy of inactivated split-virus influenza vaccine against culture-confirmed influenza in healthy adults: a prospective, randomized, placebo-controlled trial.", "Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example.", "Influenza vaccination with live-attenuated and inactivated virus-vaccines during an outbreak of disease.", "Evaluation of an attenuated, cold-recombinant influenza B virus vaccine.", "[The trivalent polymer-subunit influenza vaccine Grippol studied in a controlled epidemiological trial (1)].", "A graded-dose study of inactivated, surface antigen influenza B vaccine in volunteers: reactogenicity, antibody response and protection to challenge virus infection.", "Influenza vaccination and the risk of primary cardiac arrest.", "Clinical trial with \"R-75\" strain live, attenuated, serum inhibitor-resistant intranasal influenza B vaccine.", "Clinical trial of a subunit influenza vaccine.", "Responses to one or two doses of a deoxycholate subunit influenza vaccine in a primed population.", "An attenuated influenza virus vaccine: Reactogenicity, transmissibility, immunogenicity, and protective efficacy.", "Influenza immunization: field trial on a university campus.", "Do hospital employees benefit from the influenza vaccine? A placebo-controlled clinical trial.", "Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland.", "Impact of influenza vaccination on civilian aircrew illness and absenteeism.", "Clinical and serologic effects of live attenuated serum inhibitor-resistant influenza B vaccine in seronegative adults.", "Vaccinations and risk of central nervous system demyelinating diseases in adults." ]

[ "For evaluation of heterologous protection by live attenuated influenza virus vaccine, 42 healthy volunteers with low titers of or no antibody to A/Scotland/74 (H3N2) and A/Victoria/3/75 (H3N2) influenza viruses were given live attenuated A/Scotland/74 (H3N2) virus vaccine or placebo by the intranasal route with no resultant vaccine-related illness. Seventeen of 21 vaccine recipients and none of 21 placebo recipients developed antibody conversion. Thirty-seven days after administration of vaccine or placebo, all subjects were challenged intranasally with wild-type A/Victoria/3/75 influenza virus. Five placebo recipients and no vaccine recipients developed moderately severe illness, whereas 10 vaccine recipients and three placebo recipients developed no illness (p less than 0.025). Although 16 of 21 vaccine recipients fulfilled criteria of infection with the challenge virus, shedding of virus was significantly less frequent, less prolonged, and of significantly lower magnitude than that in the placebo recipients. Thus, live attenuated influenza virus vaccine showed a significant protective effect against illness following challenge with heterologous wild-type virus. The protective effect and the negligible side effects of this vaccine merit consideration of its use in a large-scale field trial.", "Inactivated influenza virus vaccine efficacy after annual revaccination has been reported to be less than that after first vaccination in boarding school children. We prospectively examined the immunogenicity and efficacy of this vaccine in healthy 30- to 60-year-old volunteers in Houston, Texas, over two epidemic seasons (1983-1985) encompassing outbreaks due to influenza A (H3N2 and H1N1) and influenza B viruses. A placebo group that had never (or not in recent years) received inactivated influenza virus vaccine, a group that received the vaccine for the first time (first vac), and a group given two or more recent vaccinations (multivac) were evaluated in a double-blind fashion each year. Vaccination induced higher frequencies of rise in serum antibody titer to vaccine components in first vac than in multivac volunteers, but mean postvaccination titers were similar. Clinical and virologic evaluations of illnesses during both epidemics and of influenza infections diagnosed serologically over the epidemic seasons revealed no overall reduction in illness from that in the placebo group for either vaccine group; modest reductions in influenza infection-related illness that were significant only for the multivac group against A/H3N2-related illness (55%; p less than 0.04); reduction in moderate-to-severe lower respiratory and/or systemic illness due to influenza for multivac (73%, p less than 0.025) but not first vac (15%, p greater than 0.10) volunteers during the A/H3N2 epidemic; reduction in influenza virus shedding in the multivac (54%, p less than 0.05) but not the first vac (16%, p greater than 0.10) group when compared with the placebo group for both years; and overall 63-81% reductions in documented infections with each influenza virus for both vaccine groups with the exception of A/H1N1 for the first vac group (24%, p greater than 0.10) and type B for the multivac group (58%, p = 0.067). Vaccine efficacy was only modest in these studies, but in contrast to the earlier report in boarding school children, efficacy appeared to be somewhat greater after repeated annual vaccination than after first administration.", "A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacy of inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease.", "nan", "nan", "The aim of the present case-control study was to ascertain whether, in adults, yearly repeated anti-influenza vaccinations (AIV) enhance protection against cutaneous melanoma (CM), as do repeated febrile infections. Ninety-nine new cases of histologically confirmed CM and 104 healthy controls (matched to cases for sex, age, and skin colour) selected from the general population were examined in order to ascertain their skin type, the number of nevi on both arms, and the intensity of freckles on the face and the arms; in these subjects, a structured questionnaire was used to obtain information on age, sex, education, social class, exposure and susceptibility to sunlight, history of febrile infectious diseases, and vaccinations. The odds ratio (OR) and the 95% confidence interval (CI) were estimated by commonly used methods and by fitting models of logistic regression. The risk of CM was reduced in subjects with a history of febrile (temperature above 38.5 degrees C) infections in the 5 years prior to CM surgery (cases) or interview (controls), but was increased in those with voluntary exposure to sunlight in tropical countries. By holding the above factors constant at logistic regression analysis, it was found that a history of repeated AIV (3-5 times in the last 5 years) halved the risk (OR: 0.43; CI: 0.19-1.00; p < 0.05). With the variable 'nevi on arms' included, the protective influence of repeated AIVs was observed in a similar magnitude. The inverse relationship found between melanoma and influenza vaccinations is unlikely to have depended on a bias, even if based on replies in a questionnaire, because neither the interviewers nor the interviewers were informed in advance of the working hypothesis.", "The reactogenicity, immunogenicity and protection effecacy of a serum inhibitor-resistant live attenuated influenza A/B (\"Alice\"/R-75) vaccine was determined in a group of health young volunteers. The influenza A component was derived from A/England/42/72 (H3N2) strain, and the B component from B/Hong Kong/5/72 strain. Sixty-eight subjects had hemagglutination inhibition (HAI) antibody titers to influenza A hemagglutinin (HA) antigen of less than or equal to 1:8 (\"low A\" group) and 75 had similarly low antibody titers to B HA antigen (\"low B\" group). Two inocula given 14 days apart consisted of vaccine in two doses (VV); one dose of vaccine followed by placebo (VP); or two doses of placebo (PP). The reactogenicity of the vaccine was low, with approximately 25% of subjects in both the immunized and placebo categories having symptoms mainly of respiratory nature. The A component of the vaccine was immunogenic with 90.9% of the subjects in the low A group VV category showing seroconversion. By contrast, only 20% of VV subjects in the low B group seroconverted to B antigen. The vaccine afforded significant protection againndergone a slight antigenic drift. There was no difference in protection afforded either by one or two doses of the vaccine. Thus the overall protection efficacy following at least one dose of the vaccine was 80.0% (p = .01), and in the low A group subjects it was 85.5% (p = .01).", "The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk.\n Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey.\n We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12.\n There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.", "The effects of intranasal inoculation with live attenuated, CR influenza virus vaccines on pulmonary function in healthy and asthmatic adults were evaluated in placebo-controlled, double-blind studies. In 46 healthy adult volunteers, there were no statistically significant alterations in pulmonary function as measured by spirometry and histamine bronchoprovocation tests in the first week following monovalent CR influenza virus vaccine [type A (H3N2, H1N1) and type B]. Among healthy adults with pre-inoculation PC20s less than 10 mg ml-1, 8/12 were infected following vaccination but no significant alterations occurred in histamine bronchoprovocation. In 11 asthmatic adults, no statistically significant alterations in pulmonary function, as measured by spirometry, were noted during the first 7 days postinoculation with bivalent CR influenza virus vaccine type A (H3N2 and H1N1). Postinoculation respiratory illnesses were more common in CR influenza virus vaccine recipients than placebo recipients, but they were mild, consisting of afebrile pharyngitis and transient rhinorrhea. Attenuated CR influenza virus vaccines do not appear to impair pulmonary function during the first week following immunization of healthy and asthmatic adults.", "In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce.\n To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers.\n A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs.\n Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased.\n Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings.", "An ongoing surveillance program was intensified during the 1979-1980 and the 1980-1981 influenza seasons to determine whether an increased risk of acquiring Guillain-Barré syndrome (GBS) within eight weeks after influenza vaccination existed for adults in the United States who received influenza vaccine, when compared with adult who had not been vaccinated recently. Five hundred twenty-eight cases of GBS with onset between Sept 1 and March 31, including seven following recent vaccination, were reported by participating neurologists in 1979-1980; 459 cases, including 12 following recent vaccination, were reported in 1980-1981. The relative risk of acquiring GBS following influenza vaccination--0.6 in 1979-1980 and 1.4 in 1980-1981--was not significantly different from 1.0 in either season. These results suggest that there was no increased risk of acquiring GBS associated with the influenza vaccines administered during these seasons and that the causative \"trigger agent\" in the A/New Jersey (swine) influenza vaccine administered in 1976 has not been present in subsequent influenza vaccine preparations.", "Haemagglutinating inhibiting antibody (HAI) responses were determined and clinical reactions recorded in 162 adult volunteers who received either 1 or 2 intranasal doses of 10(7-0) EID50 WRL 105 strain live influenza vaccine or placebo. After administration of a single dose of vaccine significant antibody responses were obtained in 69 (70%) of 98 volunteers with initial antibody titres of less than or equal to 1/20. Of the 70 volunteers who received a second dose of vaccine, 62 provided a further post-vaccination sample of serum, and only 3 (4-8%), who had not responded to the first dose of vaccine, produced a significant antibody response. Local, upper respiratory and constitutional symptoms were recorded more frequently after the administration of a first dose of vaccine than after placebo or a second dose of vaccine. The symptoms were of a minor nature except in one volunteer who, after the first dose of vaccine, developed influenzal symptoms followed by bronchitis.", "In 2000, an influenza vaccine was associated with unusual ocular and respiratory symptoms (known as \"oculorespiratory syndrome\" [ORS]) that possibly were due to numerous microaggregates of unsplit viruses present in the product. We assessed the potential for an improved vaccine formulation (for use in 2001-2002) to cause ORS and other symptoms in adults, using a double-blind, randomized, crossover study design. Symptoms were ascertained 24 h after 622 doses of vaccine and 626 doses of saline placebo were injected. The risk of ORS was 6.3% after vaccine injection and 3.4% after placebo injection, which yielded a significant vaccine-attributable risk of 2.9% (95% confidence interval, 0.6-5.2). ORS symptoms were mild. Significant differences in risk after injection of vaccine versus placebo existed for ocular soreness and/or itching (2.4%), coughing (1.6%), and hoarseness (1.2%). Vaccine-attributable general symptoms were infrequent. We conclude that certain mild oculorespiratory symptoms were triggered by an influenza vaccine that was otherwise minimally reactogenic and, hence, that such symptoms might be associated with influenza vaccines in general.", "Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.\n To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults.\n Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998.\n Thirteen centers across the United States.\n A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population.\n Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997.\n Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events.\n Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain.\n Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.", "This study evaluated the safety, immunogenicity, and protective efficacy of vaccines containing purified recombinant uncleaved hemagglutinin (rHA0) from influenza A/Beijing/32/92 (H3N2) virus. In a randomized, double-blinded trial, 127 adult volunteers were immunized with 15 micrograms of rHA0, 15 micrograms of rHA0 plus alum, 90 micrograms of rHA0, licensed subvirion vaccine, or saline placebo. The rHA0 vaccines caused fewer local adverse reactions than did the commercial subvirion preparation. Neutralizing hemagglutinin-specific antibody responses to 15 micrograms of rHA0 were comparable to those elicited by licensed vaccine, not enhanced by the addition of alum, and significantly increased by raising the rHA0 dose from 15 to 90 micrograms. Compared with placebo recipients, rHA0-vaccinated subjects had significantly lower rates of influenza A (H3N2) virus infection and illness during the epidemic winter season. These results suggest that influenza vaccines containing purified rHA0 may offer an advantage over licensed preparations containing egg-grown antigens by inducing equivalent protective immune responses while being potentially less reactogenic.", "A field study was undertaken in Tampa, Fla., to assess the efficacy of subcutaneous and aerosol methods of administering vaccine, and to compare the protection afforded by bivalent (A2 and B) influenza virus vaccine and by A2/Hong Kong/68 virus vaccine. Further objectives of the study included a comparison of the effectiveness of single-dose and 2-dose immunization. Approximately 2100 volunteers received, in a double-blind manner, both an injection and an aerosol administration on 2 occasions 3 weeks apart. The results showed that aerosol administration gave a lower over-all protection rate, although the booster dose seemed to have a marked effect. The protection afforded by A2/Hong Kong/68 virus vaccine was considerably greater than that afforded by the bivalent vaccine, particularly when administration was subcutaneous. Results are also given on the occurrence of side-effects and on the correlation between cigarette smoking and the occurrence of influenza-like illness.", "nan", "Although influenza causes substantial morbidity and mortality in all age groups, current recommendations emphasize annual immunization for people at high risk for complications of influenza. We conducted a double-blind, placebo-controlled trial of vaccination against influenza in healthy, working adults.\n In the fall of 1994, we recruited working adults from 18 to 64 years of age from in and around the Minneapolis-St. Paul area and randomly assigned them to receive either influenza vaccine or placebo injections. The primary study outcomes included upper respiratory illnesses, absenteeism from work because of upper respiratory illnesses, and visits to physicians' offices for upper respiratory illnesses. The economic benefits of vaccination were analyzed by estimating the direct and indirect costs associated with immunization and with upper respiratory illnesses.\n We enrolled a total of 849 subjects. Baseline characteristics were similar in the two groups. During the follow-up period, consisting of the 1994-1995 influenza season (December 1, 1994, through March 31, 1995), those who received the vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo (105 vs. 140 episodes per 100 subjects, P < 0.001), 43 percent fewer days of sick leave from work due to upper respiratory illness (70 vs. 122 days per 100 subjects, P = 0.001), and 44 percent fewer visits to physicians' offices for upper respiratory illnesses (31 vs. 55 visits per 100 subjects, P = 0.004). The cost savings were estimated to be $46.85 per person vaccinated.\n Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults.", "Some reports have suggested that influenza virus vaccine is less effective in persons that have received prior annual vaccination(s) than in those receiving it for the first time. This issue was addressed by evaluating the efficacy of annual influenza vaccinations over a 5 year period in healthy adults employing commercially-available, inactivated whole-virus vaccine. Influenza vaccination had minimal effects on overall respiratory illnesses during epidemic periods. However, it reduced influenza virus shedding by an average of 38.8% and conferred protection against influenza virus infection during each epidemic. Some variation in infection rates were noted between vaccine groups given one or more than one annual immunization, and between years, but no consistent pattern of differences was noted in relation to number of successive years of vaccination. These results suggest that the current recommendation for annual influenza vaccination of persons at special risk of serious disease and complications is appropriate, but that continued efforts to improve the effectiveness of our prophylactic measures against influenza are needed.", "nan", "To determine if a vaccine against influenza significantly decreases episodes of acute upper respiratory infection (AURI) and work absenteeism caused by AURI, in healthy adult employees of a banking entity in the city of Medellín, Colombia.\n This was a double-blind randomized placebo-controlled study with 493 volunteers. The volunteers were randomly assigned to two groups, an experimental group and a control group, with 247 and 246 employees, respectively. The experimental group participants received a dose of 0.5 mL of an influenza vaccine containing surface antigens of the strains recommended by the World Health Organization for the 1996-1997 period, with subtypes A/Wuhan/359/95 (H3N2), A/Texas/36/91 (H1N1), and B/Beijing/184/93. An illness was considered an episode of AURI when a participant reported having a sore throat, fever, and a cough lasting more than 24 hours. Evaluations were made every 2 weeks over a 6-month period; the severity of the episodes was assessed in terms of lost workdays due to AURI (defined according to the ninth revision of the International Classification of Diseases, or ICD-9), through monthly evaluations of incapacitating work absences certified by the Colombian Social Security system, over the period of a year.\n Side effects associated with the vaccine were erythema (relative risk (RR) = 8.0; P = 0.02) and local edema (RR = 4.5; P = 0.03). The proportion of the annual cumulative incidence of episodes of AURI was 78.5% for the vaccinated persons and 91.5% for those in the placebo group, with a reduction of 14%, with values between 7% and 20% (RR = 0.86; 95% confidence interval (CI) = 0.80-0.93). The annual cumulative incidence of incapacitating AURI was 15.8% in those vaccinated, with a reduction of 31% in comparison to the placebo group (22.8%), with values between 0% and 52% (RR = 0.69; 95% CI = 0.48-1.0). These levels of protection, both against more mildly symptomatic forms of AURI and those causing lost workdays, increased significantly (between 62% and 89%) in the months of May and October, when outbreaks caused by the influenza virus were confirmed in Colombia.\n The results demonstrated that the influenza vaccination strategy decreased the AURI episodes as well as the number of work absences due to AURI in the healthy adult employees of a banking entity in the city of Medellín, Colombia. The impact that influenza has on this population group is small, and the effect of this vaccination measure is greater then the influenza virus is in circulation.", "Monovalent influenza A/Victoria/3/75 whole-virus vaccines prepared by Merck Sharp and Dohme (West Point, Pa.) and Merrell-National Laboratories (Cincinnati, Ohio) and split-virus vaccines prepared by Parke, Davis and Company (Detroit, Mich.) and Wyeth Laboratories (Philadelphia, Pa.) containing 200, 400, and 800 chick cell-agglutinating units per dose were compared with a placebo in double-blind trials in which 208 adults participated. Titers of hemagglutination-inhibiting antibody of greater than or equal to 1:20 were found in greater than 80% of the volunteers 21 days after vaccination. Seroconversion, defined as a fourfold or greater increase in antibody titer, occurred more frequently among seronegative volunteers than among seropositive volunteers. The geometric mean titers obtained with the whole-virus or split-virus vaccines were not significantly different. Reaction rates had no relation to seroconversion, nor did seronegative subjects have more reactions than seropositive subjects. Local reactions from all vaccines increased with increasing dose. Significantly more overall reactions, \"bothersome\" reactions, and febrile reactions occurred in the recipients of whole-virus vaccine. Of nine volunteers who reported temperatures of greater than 100 F, one had received split-virus vaccine, seven had received whole-virus vaccine, and one had received the placebo. Most systemic reactions were mild, and all were self-limited.", "Although the cost-effectiveness and cost-benefit of influenza vaccination are well established for persons aged 65 years or older, the benefits for healthy adults younger than 65 years are less clear.\n To evaluate the effectiveness and cost-benefit of influenza vaccine in preventing influenza-like illness (ILI) and reducing societal costs of ILI among healthy working adults.\n Double-blind, randomized, placebo-controlled trial conducted during 2 influenza seasons.\n Healthy adults aged 18 to 64 years and employed full-time by a US manufacturing company (for 1997-1998 season, n = 1184; for 1998-1999 season, n = 1191).\n For each season, participants were randomly assigned to receive either trivalent inactivated influenza vaccine (n = 595 in 1997-1998 and n = 587 in 1998-1999) or sterile saline injection (placebo; n = 589 in 1997-1998 and n = 604 in 1998-1999). Participants in 1997-1998 were rerandomized if they participated in 1998-1999.\n Influenza-like illnesses and associated physician visits and work absenteeism reported in biweekly questionnaires by all participants, and serologically confirmed influenza illness among 23% of participants in each year (n = 275 in 1997-1998; n = 278 in 1998-1999); societal cost of ILI per vaccinated vs unvaccinated person.\n For 1997-1998 and 1998-1999, respectively, 95% (1130/1184) and 99% (1178/1191) of participants had complete follow-up, and 23% in each year had serologic testing. In 1997-1998, when the vaccine virus differed from the predominant circulating viruses, vaccine efficacy against serologically confirmed influenza illness was 50% (P =.33). In this season, vaccination did not reduce ILI, physician visits, or lost workdays; the net societal cost was $65.59 per person compared with no vaccination. In 1998-1999, the vaccine and predominant circulating viruses were well matched. Vaccine efficacy was 86% (P =.001), and vaccination reduced ILI, physician visits, and lost workdays by 34%, 42%, and 32%, respectively. However, vaccination resulted in a net societal cost of $11.17 per person compared with no vaccination.\n Influenza vaccination of healthy working adults younger than 65 years can reduce the rates of ILI, lost workdays, and physician visits during years when the vaccine and circulating viruses are similar, but vaccination may not provide overall economic benefits in most years. JAMA. 2000;284:1655-1663.", "Because of an increase in the number of reports of Guillian-Barre syndrome (GBS) following A/New Jersey influenza vaccination, the National Influenza Immunization Program was suspended December 16, 1976 and nationwide surveillance for GBS was begun. This surveillance uncovered a total of 1098 patients with onset of GBS from October 1, 1976, to January 31, 1977, from all 50 states, District of Columbia, and Puerto Rico. A total of 532 patients had recently received an A/New Jersey influenza vaccination prior to their onset of GBS (vaccinated cases), and 15 patients received a vaccination after their onset of GBS. Five hundred forty-three patients had not been recently vaccinated with A/New Jersey influenza vaccine and the vaccination status for 8 was unknown. Epidemiologic evidence indicated that many cases of GBS were related to vaccination. When compared to the unvaccinated population, the vaccinated population had a significantly elevated attack rate in every adult age group. The estimated attributable risk of vaccine-related GBS in the adult population was just under one case per 100,000 vaccinations. The period of increased risk was concentrated primarily within the 5-week period after vaccination, although it lasted for approximately 9 or 10 weeks.", "Trivalent cold-adapted recombinant (CR) influenza virus vaccines containing types A (H1N1 and H3N2) and B viruses were evaluated in two double-blind, placebo-controlled trials. Susceptible adults were randomly assigned to receive the following vaccines by intranasal drops 1 month apart: two doses of trivalent vaccine, bivalent CR influenza A (Bi A) vaccine followed by monovalent B (Mono B) vaccine or vice versa, or two doses of placebo. All vaccines were well tolerated. Shedding of each of the three vaccine viruses was reduced after the first dose of trivalent vaccine compared with primary vaccination with Bi A or Mono B. Shedding was also reduced after second vaccinations, whether homologous (trivalent-trivalent) or heterologous (Bi A/Mono B or Mono B/Bi A). Reduced viral shedding was associated with reduced serum antibody responses. Thus, both simultaneous and sequential inoculations of susceptible adults with CR influenza vaccine viruses result in reduced viral shedding and serum antibody responses.", "We studied the safety and immunogenicity of a nasally administered vaccine comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently associated with outer membrane proteins of Neisseria meningitidis (Proteosome) in normal, healthy adults. In a randomized, double-blind trial participants (n = 78) were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or 45 microg of each of the three HA antigens, or two nasal doses containing 30 microg of each HA, separated by 2 weeks. The vaccine was generally well tolerated in all doses tested, and in a one or two-dose schedule. A shallow vaccine reactogenicity dose-response was seen. The most common local reaction was nasal congestion, which occurred in up to 48.3% of vaccine recipients in days 0-6 after vaccine but was mild and self-limiting; this reaction was not significantly more common among active vaccine recipients than placebo recipients. Mild to moderate headache was the most commonly reported systemic reactogenicity complaint in all treatment groups, and was the only solicited complaint to increase significantly in frequency after a second active dose. No severe systemic reactions occurred. A positive and statistically significant antibody response was observed, in serum and in nasal secretions, to increasing dose for all three antigens. Serum HAI titre responses and nasal secretory IgA immune responses were elicited against all three antigens. Further testing of this nasal influenza vaccine is warranted to determine its safety and immunogenicity in these populations and its efficacy in the prevention of clinical illness.", "A cold recombinant live influenza B virus vaccine was tested in man. In comparison to a placebo, reactogenicity attributable to virus infection was slight or moderate. No revertant viruses were shed, and there was no evidence of transmission to the placebo group who were housed in close contact with the vaccinees. Serological responses to initial inoculation were moderate; 60% of vaccinees showing twofold increases in serum hemagglutination inhibition (HAI) titers gave a geometric mean titer (GMT) of 1:13. Three weeks after the first vaccination, both the vaccine and the placebo group were revaccinated with homologous live virus vaccine. The group previously given vaccine was resistant to reinfection as judged from clinical reactions and virus shedding and the GMT increased only slightly to 1:16.3. In contrast, the former placebo group responded; mild symptoms were seen, the majority shed viruses and 50% showed twofold increases in serum HAI titers to a geometric mean titer of 1:17.4.", "Numerous case reports have suggested a possible association between optic neuritis and receipt of several different vaccines. The most frequently identified vaccines associated with optic neuritis in the literature are influenza and hepatitis B, and a report describing 2 US military cases suggests an association with the currently used anthrax vaccine (anthrax vaccine adsorbed).\n To test the hypothesis that optic neuritis may be associated with anthrax, smallpox, hepatitis B, and influenza vaccines.\n We conducted a matched case-control study among US military personnel from January 1, 1998, through December 31, 2003, using the Defense Medical Surveillance System. Statistical associations between vaccine exposures and optic neuritis within 6-, 12-, and 18-week study intervals were estimated through multivariable conditional logistic regression analyses.\n A total of 1131 cases of optic neuritis and 3393 controls were matched by sex, military component, and deployment status.\n No statistically significant associations between optic neuritis and anthrax vaccine were observed for any of the 3 study intervals: 6-week interval (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.74-1.87), 12-week interval (OR, 0.92; 95% CI, 0.63-0.35), and 18-week interval (OR, 0.81; 95% CI, 0.58-1.14). Furthermore, no difference in optic neuritis risk was detected when comparing those who received no dose, 1 dose, and 2 doses of anthrax vaccine. Similarly, no statistically significant associations were observed between optic neuritis and smallpox, hepatitis B, or influenza vaccines within any of the study intervals. No vaccine to vaccine interactions were statistically significant.\n The results from this vaccine postmarketing surveillance investigation suggest that there is no association between optic neuritis and receipt of anthrax, smallpox, hepatitis B, or influenza vaccinations in the US military, whether these vaccines are administered alone or in combination. The negative findings presented here are important to the continuing discussions regarding the safety of these vaccines.", "nan", "Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor inducers of mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice. We conducted an open-label safety study followed by an observer-blind, randomized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a serum antibody response was slightly lower. The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine. Both vaccines gave more frequent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses.", "A comparative evaluation of immunological and epidemiological effectiveness of commercial live and killed vaccine preparations used simultaneously or separately was first carried out in simultaneous field trials of various methods of influenza vaccine prevention in a human population of 10,449 subjects. The advantage of simultaneous immunization was confirmed by immunological parameters and protective effect in the period of influenza A epidemic of 1983. The correlation of immunological and epidemiological effectiveness of influenza vaccines in joint or separate administration is discussed.", "A new trivalent inactivated split-virus influenza vaccine (TIV) was recently introduced in the United States. We assessed the efficacy of TIV against culture-confirmed influenza A and/or B.\n In this double-blind trial conducted from September 2006 to May 2007 in the Czech Republic and Finland, participants aged 18-64 years were randomized to receive 1 dose of TIV (n = 5103) or placebo (n = 2549). Influenza-like illnesses (ILI) (defined as at least 1 systemic symptom [fever {oral temperature, > or = 37.8 degrees C} and/or myalgia] and at least 1 respiratory symptom [cough and/or sore throat]) were identified by both active (biweekly phone contact) and passive surveillance. Nasal and throat swab specimens were collected for viral culture.\n The attack rate for culture-confirmed ILI was 3.2% in the placebo group, with most strains identified as influenza A (all except 1 were H3N2) matching the vaccine strain. There were 6 cases of influenza B, all of which were of a different lineage (Yamagata) than the vaccine strain. Vaccine efficacy against culture-confirmed influenza A and/or B due to strains antigenically matched to the vaccine was 66.9% (95% confidence interval [CI], 51.9%-77.4%; P < .001) and to any strain was 61.6% (95% CI, 46.0%-72.8%; P < .001).\n TIV is efficacious against culture-confirmed influenza in healthy adults.\n ClinicalTrials.gov identifier: NCT00363870.", "Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.\n 6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was > or = 45%. Cases of influenza like illness (defined as fever (oral temperature > or =37.8 degrees C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.\n TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).\n Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.\n Clinical trial registery: NCT00197223.", "Immunization procedures with live attenuated and inactivated vaccines were carried out on a group of young recruits at the beginning of an outbreak of infection due to an A/Victoria/3/75-related virus strain, which occurred in February 1977 in a military camp. A retrospective investigation on protection from clinical influenza was then performed in order to investigate whether immunization with live virus vaccines, administered at the beginning of an epidemic, could provide early protection from the disease. In the course of the two weeks following vaccination, laboratory-confirmed clinical influenza cases occurred in 4 subjects among the 110 volunteers of the control group which received placebo, and in 8, 7 and 4 subjects respectively of the 3 groups of about 125 individuals, each of which received one of the following vaccine preparations: (a), live attenuated A/Victoria/3/75 influenza virus oral vaccine, grown on chick embryo kidney culture; (b), live attenuated nasal vaccine, a recombinant of A/Puerto Rico/8/34 with A/Victoria/3/75 virus; and (c), inactivated A/Victoria/3/75 virus intramuscular vaccine. These data do not support the hypothesis that, during an epidemic of infection, early protection from clinical influenza can be achieved through immunization with live attenuated or inactivated influenza virus vaccines, in spite of the high immunizing capability of the vaccine preparations.", "A live, attenuated influenza B virus vaccine was evaluated in a group of students. The virus, cold-recombinant (CR) 7, was produced by recombining the attenuated cold-adapted parent, B/Ann Arbor/1/66, with a wild strain, B/Hong Kong/8/73. In ferrets, the wild strain produced histopathologic lesions in the lungs, whereas the CR strain and the attenuated parent did not. A total of 306 individuals was inoculated intranasally with either the CR virus or a placebo. After inoculation, only one symptom was significantly more common in the vaccinees than in the control subjects. That symptom, sore throat, occurred briefly in 26% of the vaccine recipients and in 10.5% of the placebo recipients. An outbreak of influenza B occurred three months after vaccination. When serologic infection rates in the two groups were compared, it was found that the vaccine had been significantly effective (P less than 0.01) in preventing infection.", "nan", "One hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 micrograms of HA or saline alone in a 0.5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response. The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 micrograms HA and least for those given 5 micrograms HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 micrograms HA, 22 (96%) showed a fourfold rise in antibody titre and all volunteers had antibody titres of greater than 40 following immunization: for volunteers given 5 micrograms HA the g.m.t. increased from 16.6 to 86.1; and for those given 10 and 20 micrograms HA the response was intermediate. Following challenge, the lowest incidence of infection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50% protection titre of serum HI antibody was estimated as 15 to 20.", "Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes, and cardiovascular mortality increases abruptly during influenza epidemics, with little evidence of a lag period. In a population-based case-control study, the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest (PCA), a major contributor to cardiovascular mortality in the community. Cases of PCA (n = 342) without prior heart disease or life-threatening comorbidity that occurred in King County, Washington, were identified from paramedic incident reports from October 1988 to July 1994. Demographically similar controls (n = 549) were identified from the community by using random digit dialing. Spouses of subjects were interviewed to assess treatment with influenza vaccine during the previous year and other risk factors. After adjustment for demographic, clinical, and behavioral risk factors, influenza vaccination was associated with a reduced risk of PCA (odds ratio = 0.51, 95 percent confidence interval: 0.33, 0.79). The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of influenza vaccination and total mortality, further studies are needed to determine whether the observed association reflects protection or selection.", "The \"R-75\" strain live, attenuated, serum inhibitor-resistant influenza B vaccine was administered intranasally by drops in two doses 14 days apart to 21 volunteers. Each vaccinee was paired with a close associate (roommate or workmate) who similarly received two doses of a placebo solution. Although about 50% of both vaccine and placebo recipients complained of symptoms after dosage, the severity of symptoms was greater in vaccine recipients. Fourfold serum hemagglutination-inhibiting antibody titer rises occurred in 38% of vaccine recipients, and four vaccines had fourfold titer rises of nasal hemagglutination-inhibiting antibody. Vaccine virus was isolated from three asymptomatic vaccine recipients. There was no virological or serological evidence of the vaccine virus spreading to placebo recipients.", "A double-blind field trial was performed comparing a subunit influenza vaccine (A/Victoria/75 and B/Hongkong/73) with placebo. A good protection against influenza was induced by the vaccine. On the basis of serological determinations (enzyme immunoassay, EIA) the incidences of influenza A and B infections were reduced within a period from 3 weeks up to 5 months after the vaccination by 88 and 68%, respectively. Three weeks after the vaccination 79% of the vaccines had acquired protective serum antibody levels (greater than or equal to 32 x 10(2) by EIA) against influenza A and 62% against influenza B, while in the control subjects protective antibody levels were measured in frequencies from 4 to 13% in subsequent serum samples. With a few exceptions antibody levels were still present in 5-month samples. Side effects were recorded within the first 3 days following the vaccination. Some minor symptoms like redness and tenderness at the vaccination site and muscle ache were reported more frequently by the vaccines than by the controls, but no more harmful systemic reactions.", "A trial with a trivalent influenza subunit vaccine prepared with sodium deoxycholate was carried out in 88 volunteers between May and November 1981. Each haemagglutinin antigen was present at 7 micrograms per dose. Fourfold or greater haemagglutination inhibition antibody (HI) responses to the H1N1 virus A/Brazil/11/78 occurred in 70% of volunteers following a single dose. For the H3N2 virus A/Bangkok/1/79 and B/Singapore/222/79 these figures were 52 and 11%, respectively. No increase in the antibody titre was noted to any of the antigens following a second vaccination dose. Antibody levels remained relatively constant six months after vaccination. A response to B/Singapore/222/79, comparable with the HI response for the influenza A antigens, was noted when serum titres were estimated by a plaque reduction procedure. No neuraminidase inhibition antibody could be detected in response to either A/Brazil/11/78 or A/Bangkok/1/79. No reactions specifically attributable to the vaccine occurred after either injection. A lower HI response to A/Brazil/11/78 was noted in volunteers 52 years of age and older, who also showed less evidence of earlier priming to this virus. Levels of nasal wash neutralizing antibodies to A/Brazil/11/78 were proportional to those detected in sera by HI tests, but were present in smaller amounts.", "nan", "nan", "Although current guidelines target hospital employees who contact high-risk patients as a high priority for influenza immunization, there are few data to support or refute this recommendation. Therefore, the authors enrolled 179 hospital employees in a randomized double-blind placebo-controlled clinical trial during the 1985-1986 influenza season. Influenza immunization was performed without serious adverse reactions and there was no increase in absenteeism attributable to the vaccination. Among those who developed clinical influenza, there was a trend toward fewer days of illness in the vaccinated group compared with the placebo group (6.0 vs. 8.0, p = 0.07). There were no statistically significant differences between subjects receiving influenza vaccine and those receiving the placebo when comparing incidences of influenza-like illness, severities of illness, and sick absenteeism. Influenza immunization of hospital employees was performed at minimal cost and risk but provided little benefit, most likely because of an unexpected drift of the prevalent influenza strain away from the vaccine type.", "After the introduction of an inactivated intranasal influenza vaccine that was used only in Switzerland, 46 cases of Bell's palsy were reported.\n We conducted a matched case-control study and a case-series analysis. All primary care physicians, ear, nose, and throat specialists, and neurologists in German-speaking regions of Switzerland were requested to identify cases of Bell's palsy diagnosed in adults between October 1, 2000, and April 30, 2001. Each physician was invited to select three control patients for each patient with Bell's palsy, with matching according to age, date of the clinic visit, and physician. Vaccination information was provided by the physicians.\n A total of 773 patients with Bell's palsy were identified. Of the 412 (53.3 percent) who could be evaluated, 250 (60.7 percent) were enrolled and matched with 722 control patients; the other 162 patients had no controls. In the case-control study, we found that 68 patients with Bell's palsy (27.2 percent) and 8 controls (1.1 percent) had received the intranasal vaccine (P<0.001). In contrast to parenteral vaccines, the intranasal vaccine significantly increased the risk of Bell's palsy (adjusted odds ratio, 84.0; 95 percent confidence interval, 20.1 to 351.9). Even according to conservative assumptions, the relative risk of Bell's palsy was estimated to be 19 times the risk in the controls, corresponding to 13 excess cases per 10,000 vaccinees within 1 to 91 days after vaccination. In the case-series analysis, the period of highest risk was 31 to 60 days after vaccination.\n This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell's palsy. This vaccine is no longer in clinical use.\n Copyright 2004 Massachusetts Medical Society", "Approximately 10% of the general population worldwide acquires influenza infection every year. Airline crews run a particularly high risk of contracting influenza and influenza-like viruses because they come in contact with hundreds of potentially infected individuals every day. Respiratory diseases are the most frequent cause of absenteeism among flight crews in airline companies. Several studies have shown the efficacy of influenza vaccination in the workplace of healthy, working adults leading to increased productivity and lower absenteeism. We conducted a double blind, randomized, placebo-controlled study on flight crews of an airline company in order to determine the safety and efficacy of a trivalent inactivated influenza vaccine in reducing illness and absences from work.\n The 813 healthy members of a Brazilian airline company were randomly assigned to receive injections of either an influenza vaccine or a placebo, with a follow-up period of 7 mo after vaccination. Primary outcomes included influenza-like illness episodes and absenteeism from work due to such episodes.\n Demographic characteristics were similar in the two groups. No significant side-effects occurred in either group. Compared to the placebo group, individuals receiving the vaccine showed 39.5% fewer episodes of flu-like illness (p < 0.001) and 26% fewer days of work lost (p = 0.03). The vaccinated group developed 33% fewer episodes of any severe flu-like illness (p < 0.01).\n The data indicates that influenza vaccination is safe in airline flight crews and may produce health-related benefits including reduced absenteeism.", "The clinical effects, nasal and serum antibody responses, and virus excretion of a live attenuated serum inhibitor-resistant influenza B virus vaccine, R75, was evaluated in 43 seronegative healthy adults by a random double-blind study. Symptom responses were minimal and were not significantly different between vaccine and placebo groups. No fevers, abnormalities in physical examination or laboratory testing developed during 4 weeks of observation. Among vaccinees, 10 (48%) developed serum hemagglutination-inhibition (HI) antibodies, 16 (76%) developed serum neutralization (N) antibodies and 4 (19%) developed nasal N antibodies. The GMT responses from study day 0 to day 28 were 4.0 to 10.4 for serum HI, 1.8 to 9.8 for serum N, and 1.0 to 1.4 for nasal N. There were no significant titer changes in the placebo group. No virus excretion was detected. Although there are some questions concerning the relationship of antibody levels to protection, the low antibody responses in this study are an indication that R75 is not sufficiently immunogenic.", "Several case reports of the onset or exacerbation of multiple sclerosis or other demyelinating conditions shortly after vaccination have suggested that vaccines may increase the risk of demyelinating diseases.\n To evaluate the association between vaccination and onset of multiple sclerosis or optic neuritis.\n Case-control study involving cases of multiple sclerosis or optic neuritis among adults 18 to 49 years of age. Data on vaccinations and other risk factors were obtained from computerized and paper medical records and from telephone interviews.\n Three health maintenance organizations.\n Four hundred forty case subjects and 950 control subjects matched on health maintenance organization, sex, and date of birth.\n None.\n Onset of first symptoms of demyelinating disease at any time after vaccination and during specified intervals after vaccination (<1 year, 1-5 years, and >5 years).\n Cases and controls had similar vaccination histories. The odds ratios (95% confidence intervals), adjusted for potential confounding variables, of the associations between ever having been vaccinated and risk of demyelinating disease (multiple sclerosis and optic neuritis combined) were 0.9 (0.6-1.5) for hepatitis B vaccine; 0.6 (0.4-0.8) for tetanus vaccination; 0.8 (0.6-1.2) for influenza vaccine; 0.8 (0.5-1.5) for measles, mumps, rubella vaccine; 0.9 (0.5-1.4) for measles vaccine; and 0.7 (0.4-1.0) for rubella vaccine. The results were similar when multiple sclerosis and optic neuritis were analyzed separately. There was no increased risk according to timing of vaccination.\n Vaccination against hepatitis B, influenza, tetanus, measles, or rubella is not associated with an increased risk of multiple sclerosis or optic neuritis." ]

[ "11730399", "9014639", "2685479", "9746022", "1951618", "12583822", "8297057", "12052127", "7823387", "2727469", "2727468", "16125589", "12213183", "10391656", "8991316", "1315663" ]

[ "Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.", "Randomization is important in studies with pain outcomes: systematic review of transcutaneous electrical nerve stimulation in acute postoperative pain.", "Meta-analysis of home-care effects on mortality and nursing-home placement.", "Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?", "Epistemology and experimentation: an examination of quality factors in research design.", "How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study.", "The efficacy of psychological, educational, and behavioral treatment. Confirmation from meta-analysis.", "Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials.", "Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.", "How study design affects outcomes in comparisons of therapy. II: Surgical.", "How study design affects outcomes in comparisons of therapy. I: Medical.", "Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.", "Funding source, trial outcome and reporting quality: are they related? Results of a pilot study.", "Impact of study quality on outcome in placebo-controlled trials of homeopathy.", "Random versus nonrandom assignment in controlled experiments: do you get the same answer?", "Impact of random assignment on study outcome: an empirical examination." ]

[ "To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.\n Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.\n Full-length randomized trials.\n Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.\n Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.\n Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.", "We set out to examine the evidence for the importance of randomization of transcutaneous electrical nerve stimulation (TENS) in acute postoperative pain. Controlled studies were sought; randomization and analgesic and adverse effect outcomes were summarized. Forty-six reports were identified by searching strategies. Seventeen reports with 786 patients could be regarded unequivocally as randomized controlled trials (RCT) in acute postoperative pain. No meta-analysis was possible. In 15 of 17 RCT, we judged there to be no benefit of TENS compared with placebo. Of the 29 excluded trials, 19 had pain outcomes but were not RCT; in 17 of these 19 TENS studies, the authors concluded that TENS had a positive analgesic effect. No adverse effects were reported. Non-randomized studies overestimated treatment effects.", "This meta-analysis was designed to illustrate how the relatively new discipline of meta-analysis could be employed in health-services research. In pursuit of this goal, the results of 13 studies on the effect of home care on mortality and nursing-home placements were examined. The analysis demonstrated a small, beneficial effect of home care on mortality, which fell short of statistical significance. Study-to-study variation in the odds ratio was found that was not strongly associated with differences in the study samples, designs, or interventions as categorized here. The analysis produced stronger evidence of a reduction in nursing-home placements. In this case, differences in study design explained much of the heterogeneity in results, with the randomized controlled trials showing considerably weaker effects. The analysis also provides insight into the benefits and limitations of alternative meta-analytic methods. The \"odd man out\" method recently described by Walker et al. detected statistically significant heterogeneity of effects across studies for nursing-home placement, but not for mortality. Loglinear modeling made it easier to detect and explore study-to-study variation in home-care effects.", "Few meta-analyses of randomised trials assess the quality of the studies included. Yet there is increasing evidence that trial quality can affect estimates of intervention efficacy. We investigated whether different methods of quality assessment provide different estimates of intervention efficacy evaluated in randomised controlled trials (RCTs).\n We randomly selected 11 meta-analyses that involved 127 RCTs on the efficacy of interventions used for circulatory and digestive diseases, mental health, and pregnancy and childbirth. We replicated all the meta-analyses using published data from the primary studies. The quality of reporting of all 127 clinical trials was assessed by means of component and scale approaches. To explore the effects of quality on the quantitative results, we examined the effects of different methods of incorporating quality scores (sensitivity analysis and quality weights) on the results of the meta-analyses.\n The quality of trials was low. Masked assessments provided significantly higher scores than unmasked assessments (mean 2.74 [SD 1.10] vs 2.55 [1.20]). Low-quality trials (score < or = 2), compared with high-quality trials (score > 2), were associated with an increased estimate of benefit of 34% (ratio of odds ratios [ROR] 0.66 [95% CI 0.52-0.83]). Trials that used inadequate allocation concealment, compared with those that used adequate methods, were also associated with an increased estimate of benefit (37%; ROR=0.63 [0.45-0.88]). The average treatment benefit was 39% (odds ratio [OR] 0.61 [0.57-0.65]) for all trials, 52% (OR 0.48 [0.43-0.54]) for low-quality trials, and 29% (OR 0.71 [0.65-0.77]) for high-quality trials. Use of all the trial scores as quality weights reduced the effects to 35% (OR 0.65 [0.59-0.71]) and resulted in the least statistical heterogeneity.\n Studies of low methodological quality in which the estimate of quality is incorporated into the meta-analyses can alter the interpretation of the benefit of intervention, whether a scale or component approach is used in the assessment of trial quality.", "Forty-four research articles published in the occupational therapy literature were examined to determine the effect of design quality on study outcome. All 44 of the studies examined involved a parallel-groups comparison design. Twenty-two of the studies included random assignment of subjects to various groups, and the remaining 22 investigations used some nonrandom method to determine subject allocation. A standardized metric (i.e., effect size) was used to determine the effect of the independent variable in the 44 studies. The data analysis revealed that effect-size values were not significantly different between studies that involved random assignment and those not involving random assignment. The argument is made that such design characteristics as random assignment should be examined as moderator variables in any attempt to synthesize findings from multiple studies. Such an approach would treat the design used in a study as one of many possible variables that could influence the outcome. This approach would modify the a priori assumption that one research design is inherently superior to another regardless of the research question or context.", "nan", "Conventional reviews of research on the efficacy of psychological, educational, and behavioral treatments often find considerable variation in outcome among studies and, as a consequence, fail to reach firm conclusions about the overall effectiveness of the interventions in question. In contrast meta-analytic reviews show a strong, dramatic pattern of positive overall effects that cannot readily be explained as artifacts of meta-analytic technique or generalized placebo effects. Moreover, the effects are not so small that they can be dismissed as lacking practical or clinical significance. Although meta-analysis has limitations, there are good reasons to believe that its results are more credible than those of conventional reviews and to conclude that well-developed psychological, educational, and behavioral treatment is generally efficacious.", "Specific features of trial quality may be associated with exaggeration or shrinking of the observed treatment effect in randomized studies. Therefore, assessment of trial quality is often used in meta-analysis. However, the degree to which specific quality measures are associated with treatment effects has not been well established across a broad range of clinical areas.\n To determine if quality measures are associated with treatment effect size in randomized controlled trials (RCTs).\n Quality measures from published quality assessment scales were evaluated in RCTs included in meta-analyses from 4 medical areas (cardiovascular disease, infectious disease, pediatrics, and surgery). Included meta-analyses incorporated at least 6 RCTs, examined dichotomous outcomes, and demonstrated significant between-study heterogeneity in the odds ratio (OR) scale.\n Relative ORs comparing overall treatment effect (summary OR) of high vs low-quality studies, as determined by each quality measure, with relative ORs less than 1 indicating larger treatment effect in low-quality studies.\n Twenty-four quality measures were analyzed for 276 RCTs from 26 meta-analyses. Relative ORs of high vs low-quality studies for these quality measures ranged from 0.83 to 1.26; none was statistically significantly associated with treatment effect. The proportion of studies fulfilling specific quality measures varied widely in the 4 medical areas. In analyses limited to specific medical areas, placebo control, multicenter studies, study country, caregiver blinding, and statistical methods were significantly associated with treatment effect on 7 occasions. These relative ORs ranged from 0.40 to 1.74. However, the directions of these associations were not consistent.\n Individual quality measures are not reliably associated with the strength of treatment effect across studies and medical areas. Although use of specific quality measures may be appropriate in specific well-defined areas in which there is pertinent evidence, findings of associations with treatment effect cannot be generalized to all clinical areas or meta-analyses.", "To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects.\n An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects.\n Meta-analyses from the Cochrane Pregnancy and Childbirth Database.\n The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding.\n Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%.\n This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.", "We analysed the results of 221 comparisons of an innovation with a standard treatment in surgery published in six leading surgery journals in 1983 to relate features of study design to the magnitude of gain. For each comparison we measured the gain attributed to the innovation over the standard therapy by the Mann-Whitney statistic and the difference in proportion of treatment successes. For primary treatments (aimed at curing or ameliorating a patient's principal disease), an average gain of 0.56 was produced by 20 randomized controlled trials. This was less than the 0.62 average for four non-randomized controlled trials, 0.63 for 19 externally controlled trials, and 0.57 for 73 record reviews (0.50 represents a toss-up between innovation and standard). For secondary therapies (used to prevent or treat complications of therapy), the average gain was 0.53 for 61 randomized controlled trials, 0.58 for eleven non-randomized controlled trials, 0.54 for eight externally controlled trials, and 0.55 for 18 record reviews. Readers of studies evaluating new treatments, particularly for primary treatments, may consider adjustment of the gain according to the study type.", "We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old. Overall we rated 87 per cent of new therapies as improvements over standard therapies. The mean gain (measured by the Mann-Whitney statistic) was relatively constant across study designs, except for non-randomized controlled trials with sequential assignment to therapy, which showed a significantly higher likelihood that a patient would do better on the innovation than on standard therapy (p = 0.004). Randomized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials (p = 0.02). Any evaluation of an innovation may include both bias and the true efficacy of the new therapy, therefore we may consider making adjustments for the average bias associated with a study design. When interpreting an evaluation of a new therapy, readers should consider the impact of the following average adjustments to the Mann-Whitney statistic: for trials with non-random sequential assignment a decrease of 0.15, for non-double-blind randomized controlled trials a decrease of 0.11.", "Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias.\n Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models.\n 110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials).\n Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.", "There has been increasing concern regarding the potential effects of the commercialization of research.\n In order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment.\n Sixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p=.461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome.\n It is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE.", "We investigated the influence of indicators of methodological quality on study outcome in a set of 89 placebo-controlled clinical trials of homoeopathy in three different ways: (1) The results of studies meeting single criteria (explicit statement of random allocation, allocation concealment, double-blinding, completeness of follow-up) of methodological quality were compared with those of studies not meeting the criteria in univariate and multivariate analyses; (2) The results of studies scoring above and below predefined scores in two quality assessment scales were compared; (3) Primary studies were consecutively entered into a cumulative meta-analysis according to the summary scores derived from the quality assessment scales. All analyses were performed using meta-regression methods. Studies that were explicitly randomized and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria. In the cumulative meta-analyses, there was a trend for increasing effect sizes when more studies with lower-quality scores were added. However, there was no linear relationship between quality scores and study outcome. We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results. Because summarizing disparate study features into a single score is problematic, meta-regression methods simultaneously investigating the influence of single study features seem the best method for investigating the impact of study quality on outcome.", "Psychotherapy meta-analyses commonly combine results from controlled experiments that use random and nonrandom assignment without examining whether the 2 methods give the same answer. Results from this article call this practice into question. With the use of outcome studies of marital and family therapy, 64 experiments using random assignment yielded consistently higher mean post-test effects and less variable posttest effects than 36 studies using nonrandom assignment. This difference was reduced by about half by taking into account various covariates, especially pretest effect size levels and various characteristics of control groups. The importance of this finding depends on (a) whether one is discussing meta-analysis or primary experiments, (b) how precise an answer is desired, and (c) whether some adjustment to the data from studies using nonrandom assignment is possible. It is concluded that studies using nonrandom assignment may produce acceptable approximations to results from randomized experiments under some circumstances but that reliance on results from randomized experiments as the gold standard is still well founded.", "Sixty research investigations published in the biomedical literature were analyzed to examine the effect of design attributes on outcome. All 60 studies included a controlled trial involving a pretest, a therapeutic intervention, and a posttest across at least two groups. Thirty of the trials used random assignment of participants to treatment or control conditions and 30 trials employed some nonrandom method of subject assignment. Trial results were aggregated and evaluated by comparing effect sizes for the primary statistical test of the hypothesis. Data analysis revealed that the trial results, as measured by effect size, did not vary across therapeutic trials using random assignment versus those using nonrandom allocation of subjects. The impact of design attributes in the interpretation of multiple clinical trials addressing a similar research question is examined. The argument is made that various design attributes frequently associated with methodological quality should be considered as important moderator variables and their influence on trial outcome should not be assumed a priori but rather examined empirically." ]

[ "20097417", "15136392", "19097848", "14625336", "10934078", "19797133" ]

[ "Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.", "A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia.", "[Duration of antibiotic therapy for ventilator-associated pneumonia: comparison of 7 and 10 days. A pilot study].", "Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.", "Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription.", "Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study." ]

[ "Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.\n In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.\n Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001).\n A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.\n Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "To evaluate an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia (VAP).\n Prospective, randomized, controlled clinical trial.\n A medical ICU from a university-affiliated urban teaching hospital.\n Between April 2002 and July 2003, 290 patients completed the clinical trial.\n Patients were assigned to have the duration of antibiotic treatment for VAP determined by an antibiotic discontinuation policy (discontinuation group) or their treating physician teams (conventional group).\n Severity of illness using APACHE (acute physiology and chronic health evaluation) II score (22.8 +/- 9.0 vs 23.2 +/- 9.4, p = 0.683) [mean +/- SD] and the clinical pulmonary infection score (7.1 +/- 0.9 vs 7.2 +/- 0.9, p = 0.222) were similar for both patient groups. The duration of antibiotic treatment for VAP was statistically shorter among patients in the discontinuation group compared to patients in the conventional antibiotic management group (6.0 +/- 4.9 days vs 8.0 +/- 5.6 days, p = 0.001). The occurrence of a secondary episode of VAP was not statistically different between these two groups (17.3% vs 19.3%, p = 0.667). Hospital mortality (32.0% vs 37.1%, p = 0.357) and ICU length of stay (6.8 +/- 6.1 days vs 7.0 +/- 7.3 days, p = 0.798) were also statistically similar.\n The application of an antibiotic discontinuation policy for clinically suspected VAP was associated with a decrease in the overall duration of antibiotic treatment. These findings suggest that shorter courses of empiric antibiotic therapy for patients treated for clinically suspected VAP can be safely achieved.", "To compare the efficiency of a 7-day antibiotics regimen with a 10-day regimen for ventilator-associated pneumonia (VAP).\n Prospective randomized study.\n Adults patients ventilated for more than 48 hours in the intensive care unit (ICU) with a clinical diagnosis of VAP documented by positive quantitative cultures of tracheal aspiration were included in this study. All included patients were randomized in two groups. Ten-day group: 10 days antibiotic therapy, and 7-day group: 7 days antibiotic therapy. Primary judgment criteria were 14- and 28-day mortality, the number of days without antibiotics. Secondary judgments criteria were rate of recurrent pulmonary infection, the evolution of the clinical pulmonary infection scores (CPIS), the length of ICU stay and the length of mechanical ventilation.\n Thirty patients were included in this study (16 in the 10-day group and 14 in the 7-day group). The demographic and clinical characteristics of the groups assigned to receive antibiotic therapy for 7 or 10 days were generally similar. The 14-day and 28-day mortality rate following VAP onset were 31.2 and 37.5% in the 10-day group and 7.1 and 35.7% in the 7-day group. The difference was not significant. The number of day without antibiotics and without mechanical ventilation turned out: 1.75 and 2.06 days versus 4.14 and 3.43 days in the 10-day group and 7-day group respectively, the recurrent rate of pulmonary infection (12.5% versus 14.3%, p=0.6), the length of stay in the ICU (27.7 days versus 26.0 days, p=0.8) and the evolution of the CPIS were no different in the two groups.\n In patients with microbiologically confirmed VAP who received appropriate empirical antibiotic therapy, a 7-day antibiotic regimen was as efficient clinically and microbiologically as a 10-day antibiotic regimen with a reduction of antibiotic use.", "The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU).\n To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP.\n Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002.\n A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician.\n Primary outcome measures-death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days-were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis.\n Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], -3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, -3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation-free days, the number of organ failure-free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P =.04).\n Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.", "Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic \"blind\" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90% (38 of 42) of the patients in the standard as therapy compared with 28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality.", "In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia." ]

[ "1353742", "8888725" ]

[ "Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial.", "n-3 fatty acids only delay early relapse of ulcerative colitis in remission." ]

[ "The effect of fish oil on the course of ulcerative colitis was investigated in a randomised blinded controlled study. Eighty seven patients received supplements of 20 ml HiEPA fish oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive oil placebo daily for one year. The oils were given in addition to standard drug therapy and trial entry was stratified for disease activity. Fish oil significantly increased the eicosapentaenoic acid content of rectal mucosa to 3.2% of total fatty acids at six months, compared with 0.63% for patients on olive oil. This was associated with increased synthesis of leukotriene B5, and 53% suppression of leukotriene B4 synthesis by ionophore--stimulated neutrophils. Leukotriene B4 suppression persisted for at least two months after treatment was stopped. Treatment with fish oil resulted in measurable, but only limited clinical benefit. For patients entering the trial in relapse (n = 53), there was a significant reduction in corticosteroid requirement after one and two months treatment. There was a trend towards achieving remission (off corticosteroids) faster in the patients on fish oil, although differences were not significant. For patients in remission at trial entry or during the trial (n = 69), there was no significant difference in the rate of relapse by log rank analysis. We conclude that fish oil supplementation produces a modest corticosteroid sparing effect in active disease, but there is no benefit in maintenance therapy.", "Relapse prevention by dietary n-3 fatty acids (5.1 g/day) was studied in a double-blind, placebo-controlled trial of 64 patients with ulcerative colitis in remission and off steroids. 5-ASA compounds were stopped three months after randomization and clinical disease activity monitored for two years. Macroscopic and histologic activity and extension was assessed by colonoscopy at entry and at exit. Both treatment groups were well matched at start. Nine patients on placebo and eight on n-3 fatty acids stopped taking their medication prematurely. Actuarial relapse-free survival was improved by n-3 fatty acids only during months 2 and 3 (2P < 0.05-0.01), but cumulative relapse rate at two years was similar for those taking placebo (18/33 = 55%) and n-3 fatty acids (18/31 = 58%). There was also no consistent difference in clinical, macroscopic, and histologic disease activity between treatment groups. The n-3 fatty acids temporarily retard, but do not prevent, relapse of ulcerative colitis." ]

[ "17705950", "17593956", "16721396", "8450402", "8853729", "14600517", "19117833", "15640476", "17414930", "9764785", "16479521", "18541571", "9498439", "10197378", "7625499", "9928729", "11930332", "15661475", "16940855", "18471061", "10753259", "16868496", "16571156", "19179490", "16310552", "10048684", "9605804", "12501132", "17242315" ]

[ "Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial.", "Zinc or multiple micronutrient supplementation to reduce diarrhea and respiratory disease in South African children: a randomized controlled trial.", "A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome.", "Beta-carotene in HIV infection.", "Beta-carotene in HIV infection: an extended evaluation.", "A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok.", "Effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents.", "Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania.", "Effect of micronutrients and iron supplementation on hemoglobin, iron status, and plasma hepatitis C and HIV RNA levels in female injection drug users: a controlled clinical trial.", "Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects.", "Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality.", "Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes.", "Vitamin A supplementation and human immunodeficiency virus load in injection drug users.", "Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a randomized controlled trial.", "The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women.", "Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women.", "Vitamin A supplementation and human immunodeficiency virus type 1 shedding in women: results of a randomized clinical trial.", "Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children in Uganda: A controlled clinical trial.", "Randomized controlled trial of zinc supplementation for persistent diarrhea in adults with HIV-1 infection.", "A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis.", "Effect of vitamin A therapy on serologic responses and viral load changes after influenza vaccination in children infected with the human immunodeficiency virus.", "Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial.", "The effect of multi-vitamin/mineral supplementation on mortality during treatment of pulmonary tuberculosis: a randomised two-by-two factorial trial in Mwanza, Tanzania.", "Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.", "Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.", "A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania.", "Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania.", "Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants.", "Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial." ]

[ "Zomba and Blantyre, Malawi, Africa.\n To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB).\n A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months.\n A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults.\n Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.", "Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain.\n To determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence.\n Randomized, double-blind, controlled trial.\n Rural community in South Africa.\n THREE COHORTS: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers.\n Children received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly.\n Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker.\n Among HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts.\n When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.\n ClinicalTrials.gov NCT00156832.", "This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients.\n A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial.\n Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN).\n Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits.\n All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120,000 IU (72 mg) of beta-carotene daily. Follow-up was quarterly at routine clinic visits.\n Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration <1.0 micromol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (P < 0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P = 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P = 0.04) or higher baseline CD4 T-lymphocyte counts (P = 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P = 0.03).\n Low serum carotene concentration is common in AIDS patients and predicts death. Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency. Further studies are needed to corroborate findings and elucidate mechanism of action.", "beta-Carotene has been reported to have an immunostimulatory effect. Recent studies suggest that beta-carotene supplementation can increase CD4 counts in HIV-infected patients. Our double-blind, placebo-controlled clinical trial was designed to test the efficacy of beta-carotene in raising CD4 counts in HIV-infected patients. Twenty-one HIV-seropositive patients were randomized to receive either beta-carotene, 180 mg/day or placebo for 4 weeks, and then crossed over to receive the alternative treatment for the following 4 weeks. beta-Carotene resulted in a statistically significant increase in total WBC count (p = 0.01), % change in CD4 count (p = 0.02), and % change in CD4/CD8 ratios (p = 0.02) compared to placebo. The absolute CD4 count, absolute CD4/CD8 ratio, and total and B-lymphocytes all increased on carotene and fell during placebo, but these differences did not reach statistical significance. No toxicity was observed on either treatment. beta-Carotene appears to have an immunostimulatory effect in HIV-infected patients. Further studies are needed to demonstrate whether beta-carotene has a role as adjunct therapy in treatment of HIV-infected patients.", "Several small short-term intervention studies have suggested that beta-carotene supplementation in HIV-infected patients can increase the number of various immune cells including CD4 cells. This prospective double-blinded study was designed to investigate whether beta-carotene supplementation would result in this immuno-enhancement in a larger number of patients over a longer time period.\n HIV-positive patients were randomly assigned to receive either 60 mg beta-carotene orally three times daily or a matched placebo. In addition, all patients received a multivitamin supplement. Patients were evaluated at baseline, 1 month, and 3 months for T-cell quantitative subsets, natural killer cells, HIV p24 antigen, beta-carotene levels, complete blood counts and chemistry batteries. Body weights and Karnofsky scores were evaluated at each visit.\n Seventy-two patients signed informed consent forms and entered the study. Except for serum beta-carotene concentration, there were no statistically significant differences (P < 0.05) between the treatment (60 mg beta-carotene three times daily and multivitamins) and placebo (placebo and multivitamins) groups at baseline or after either 1 or 3 months of treatment.\n Earlier studies suggesting that beta-carotene supplementation increased levels of immune cells in HIV-infected patients were not replicated in this study. The addition of a multivitamin supplement to both arms of this study may have masked any difference between the two groups. However, on the basis of the results of this study, we would not recommend supplementation with high doses of beta-carotene for HIV-infected patients.", "To examine the impact of high-dose multiple micronutrient supplementation on survival and disease progression among HIV-infected individuals in Thailand.\n Randomized placebo-controlled trial.\n Four-hundred and eighty-one HIV-infected men and women living in and around Bangkok with CD4 cell counts in the range 50 x 10(6)- 550 x 10(6)/l were randomized to receive micronutrients or placebo for a period of 48 weeks. Trial participants were examined clinically 12-weekly and tested for CD4 cell count 24-weekly. A subset were tested for HIV plasma viral load at 48 weeks.\n Seventy-nine (16%) trial participants were lost to follow-up and 23 (5%) died. The death rate was lower in the micronutrients arm with the mortality hazard ratios [95% confidence interval (CI)] of 0.53 (0.22-1.25; P = 0.1) overall and 0.37 (0.13-1.06; P = 0.052) and 0.26 (0.07-0.97; P = 0.03) among those with CD4 cell counts < 200 x 10(6)/l and < 100 x 10(6)/l respectively. There was no impact on CD4 cell count or plasma viral load.\n Multiple micronutrient supplementation may enhance the survival of HIV-infected individuals with CD4 cell counts < 200 x 10(6)/l. This could have important public health implications in the developing world where access to antiretrovirals remains poor. The clinical findings need to be reproduced in other settings and the mechanism, which appears to be independent of change in CD4 cell count, merits further investigation.", "Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States. In light of the importance of vitamin D for skeletal and nonskeletal health, including innate immunity, developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research. The objective of this study was to evaluate the effect of administration of oral cholecalciferol, 100,000 IU every 2 months, and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations, serum and urine calcium, and HIV disease progression during a 12-month period.\n HIV-infected children and adolescents who were aged 6 to 16 years were randomly assigned to receive vitamin D (100,000 IU bimonthly) and calcium (1 g/day; n = 29) or double placebo (n = 27). Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay, albumin-corrected calcium concentrations, and spot urinary calcium-creatinine ratios were determined monthly.\n No abnormalities in serum calcium concentration were observed. One participant who received placebo developed hypercalciuria. No group differences were seen in the change in CD4 count or CD4% or viral load during 12 months. The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group, as was the monthly serum 25-hydroxyvitamin D area under the curve. After completing 12 months of study, 2 (6.7%) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration <20 ng/mL compared with 14 (50%) in the placebo group. Twelve (44.4%) in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration of > or =30 ng/mL compared with 3 (11.1%) in the placebo group.\n Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100,000 IU every 2 months, together with 1 g/day calcium, is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations.", "In observational studies, the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women.\n We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women.\n Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the experimental assignment.\n We observed no significant differences in birth weight, duration of gestation, or fetal and neonatal mortality between women in the zinc and placebo groups. Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups. However, the rise in hemoglobin over this period was significantly lower (P = 0.03) in the zinc group (x +/- SD: 11.5 +/- 17.9 g/L) than in the placebo group (15.2 +/- 18.6 g/L). Similarly, the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group (P < 0.01 and P = 0.01, respectively). Zinc had no effect on CD4(+), CD8(+), or CD3(+) cell counts during the follow-up period.\n Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations, no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women.", "Iron deficiency is common among female injection drug users, but it is unclear whether iron supplementation can reduce anemia and improve iron status without increasing plasma hepatitis C virus (HCV) or HIV RNA levels.\n We conducted a phase 3, double-blind, randomized, controlled clinical trial of daily micronutrients with 18 mg of iron (iron group) versus micronutrients without iron (control group) for 12 months among hepatitis C-positive female injection drug users in Baltimore, Maryland. The main outcome measures were hemoglobin, markers of iron status, plasma HCV RNA, plasma HIV RNA, and liver enzymes at 6 and 12 months of follow-up.\n Four hundred fifty-eight women (320 HIV-negative and 138 HIV-positive) enrolled in the trial. There were no significant differences in the proportion of women with anemia, ferritin<30 ng/mL, log10 plasma HCV RNA, or log10 plasma HIV RNA between treatment groups at enrollment. The proportion with anemia in the iron and control groups, respectively, was 20.7% versus 31.3% (P=0.026) at 6 months and 26.2% versus 30.4% (P=0.5) at 12 months; with ferritin<30 ng/mL, the proportion was 29.2% versus 55.5% (P<0.0001) at 6 months and 26.2% versus 46.9% (P=0.0018) at 12 months. In the iron and control groups, respectively, mean log10 plasma HCV RNA (IU/mL) was 5.2 versus 5.2 (P=0.86) at 6 months and 5.4 versus 5.3 (P=0.6) at 12 months. Among HIV-positive subjects, mean log10 plasma RNA (copies/mL) in the iron and placebo groups, respectively, was 3.8 versus 3.7 (P=0.75) at 6 months and 3.7 versus 4.1 (P=0.19) at 12 months. There were no significant differences in liver enzyme levels between the treatment groups at enrollment, 6 months, and 12 months.\n A daily micronutrient supplement with iron can reduce anemia and improve iron status in female injection drug users without increasing plasma HCV or HIV RNA levels or altering liver enzymes.", "The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans.\n A randomized placebo-controlled, double-blind study.\n Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded.\n The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group.\n Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.", "Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants.\n A total of 14,110 mother-infant pairs were enrolled < or =96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 x 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis.\n Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) positive [corrected] for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P=.01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ~2-fold higher mortality (P< or =.05).\n Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas.", "In observational studies, adequate selenium status has been associated with better pregnancy outcomes and slowed HIV disease progression.\n We investigated the effects of daily selenium supplements on CD4 cell counts, viral load, pregnancy outcomes, and maternal and infant mortality among 913 HIV-infected pregnant women.\n In this randomized, double-blind, placebo-controlled trial, eligible women between 12 and 27 wk of gestation were given daily selenium (200 mug as selenomethionine) or placebo as supplements from recruitment until 6 mo after delivery. All women received prenatal iron, folic acid, and multivitamin supplements irrespective of experimental assignment.\n The selenium regimen had no significant effect on maternal CD4 cell counts or viral load. Selenium was marginally associated with a reduced risk of low birth weight [relative risk (RR) = 0.71; 95% CI: 0.49, 1.05; P = 0.09] and increased risk of fetal death (RR = 1.58; 95% CI = 0.95, 2.63; P = 0.08), but had no effect on risk of prematurity or small-for-gestational age birth. The regimen had no significant effect on maternal mortality (RR = 1.02; 95% CI = 0.51, 2.04; P = 0.96). There was no significant effect on neonatal or overall child mortality, but selenium reduced the risk of child mortality after 6 wk (RR = 0.43; 95% CI = 0.19, 0.99; P = 0.048).\n Among HIV-infected women from Dar es Salaam, Tanzania, selenium supplements given during and after pregnancy did not improve HIV disease progression or pregnancy outcomes, but may improve child survival. This trial was registered at clinicaltrials.gov as NCT00197561.", "The use of vitamin A therapy during human immunodeficiency virus (HIV) infection is under clinical investigation, and vitamin A could potentially modulate HIV replication because the virus genome contains a retinoic acid response element. A randomized, double-masked, placebo-controlled clinical trial was conducted to determine the impact of single high-dose vitamin A supplementation, 60-mg retinol equivalent (200,000 IU), on HIV load and CD4 lymphocyte count. HIV-infected injection drug users (120) were randomly allocated to receive vitamin A or placebo. Plasma vitamin A level, CD4 lymphocyte count, and HIV load were measured at baseline and 2 and 4 weeks after treatment. Vitamin A supplementation had no significant impact on HIV load or CD4 lymphocyte count at 2 and 4 weeks after treatment. This study suggests that high-dose vitamin A supplementation does not influence HIV load.", "As HIV has spread through sub-Saharan Africa, persistent diarrhoea has emerged as a major problem in hospitals and in the community in severely affected areas. We have previously demonstrated that antiprotozoal therapy with albendazole reduces diarrhoea in AIDS patients in urban Zambia. This trial was designed to test the hypothesis that the clinical response to albendazole might be improved by oral micronutrient supplementation.\n Randomized, placebo-controlled trial.\n Home care service of Ndola Central Hospital, Zambia.\n HIV-seropositive patients with persistent diarrhoea.\n Patients were randomized to albendazole plus vitamins A, C and E, selenium and zinc orally or albendazole plus placebo, for 2 weeks.\n Time with diarrhoea following completion of treatment; mortality; adverse events.\n Serum vitamin A and E concentrations before treatment were powerful predictors of early mortality, but supplementation did not reduce time with diarrhoea or mortality during the first month, even after taking into account initial vitamin A or E concentrations, CD4 cell count or clinical markers of illness severity. Serum concentrations of vitamins A and E did not increase significantly in supplemented patients compared with those given placebo, and there were no changes in CD4 cell count or haematological parameters. No adverse events were detected except those attributable to underlying disease.\n Although micronutrient deficiency is predictive of early death in Zambian patients with the diarrhoea-wasting syndrome, short-term oral supplementation does not overcome it nor influence morbidity or mortality.", "The effects of vitamin A supplementation on morbidity of children born to human immunodeficiency virus (HIV)-infected women were evaluated in a population where vitamin A deficiency is not endemic.\n A randomized, placebo-controlled trial of vitamin A supplementation was carried out in 118 offspring of HIV-infected women in Durban, South Africa. Those assigned to receive a supplement were given 50,000 IU of vitamin A at 1 and 3 months of age; 100,000 IU at 6 and 9 months; and 200,000 IU at 12 and 15 months. Morbidity in the past month was then recalled at each follow-up visit. Analysis was based on 806 child-months.\n Among all children, the supplemented group had lower overall morbidity than the placebo group (OR = 0.69; 95% confidence interval [CI] = 0.48, 0.99). Among the 85 children of known HIV status (28 infected, 57 uninfected), morbidity associated with diarrhea was significantly reduced in the supplemented infected children (OR = 0.51; 95% CI = 0.27, 0.99), whereas no effect of supplementation on diarrheal morbidity was noted among the uninfected children.\n In a population not generally vitamin A deficient, vitamin A supplementation for children of HIV-infected women appeared to be beneficial, reducing morbidity. The benefit was observed particularly for diarrhea among HIV-infected children.", "Vitamin A supplementation has been suggested for treatment and prevention of HIV infection. However, some in vitro data indicate that vitamin A may activate HIV. Randomly, 40 HIV-seropositive women of reproductive age were allocated to receive a single oral dose of 9900 micromol (300,000 IU) vitamin A or placebo. Plasma HIV-1 RNA concentration, total lymphocytes, selected lymphocyte subsets and activation markers, and in vitro lymphocyte proliferation to phytohemagglutinin (PHA) and Candida were measured before dosing and at various time points over an 8-week follow-up period. No differences were found between treatment groups in the frequency of signs or symptoms of acute vitamin A toxicity, nor were differences evident in any lymphocyte subset or activation marker at any time during follow-up. Mean and median viral load concentration at each time point and change in viral load from baseline to each follow-up point did not differ between treatment groups. No difference was measured between treatment groups in the proportion of women who responded to PHA or Candida. This study provides no evidence that high dose vitamin A supplementation of HIV-infected women is associated with significant clinical or immunologic adverse effects.", "Observational studies have associated vitamin A deficiency with vaginal shedding of human immunodeficiency virus (HIV) type 1-infected cells and mother-to-child HIV-1 transmission. To assess the effect of vitamin A supplementation on vaginal shedding of HIV-1, a randomized, double-blind, placebo-controlled trial of 6 weeks of daily oral vitamin A (10,000 IU of retinyl palmitate) was conducted among 400 HIV-1-infected women in Mombasa, Kenya. At follow-up, there was no statistically significant difference in the prevalence of HIV-1 DNA (18% vs. 21%, P=.4) or the quantity of HIV-1 RNA (3.12 vs. 3.00 log(10) copies/swab, P=1.0) in vaginal secretions of women receiving vitamin A, compared with women receiving placebo. No significant effect of supplementation on plasma HIV-1 load or CD4 or CD8 cell counts was observed, and no effect was seen among women who were vitamin A deficient at baseline. Vitamin A supplementation is unlikely to decrease the infectivity of women infected with HIV-1.", "We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV).\n We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy.\n After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations.\n Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries.", "In children, zinc supplementation reduces the incidence and severity of diarrhea.\n HIV-infected adults with > or =7 days of diarrhea recruited at 3 tertiary hospitals in Lima, Peru, received a zinc sulfate capsule containing 50 mg of elemental zinc twice daily or an identical placebo for 14 days. Outcomes included persistence of diarrhea at day 14 and time until cessation of diarrhea.\n The 81 subjects randomized to zinc and 78 randomized to placebo were comparable at baseline, except for higher prevalences of certain enteric pathogens in the zinc group; complete follow-up rates were 62% and 69%, respectively. Zinc concentrations were consistent with zinc deficiency at follow-up in 94% of placebo recipients and 66% of zinc recipients (P = 0.01). Persistence of diarrhea at day 14 according to follow-up interview (60% for zinc-treated patients and 57.4% for placebo-treated patients) or to patient diary (42.2% vs. 31.9%) did not differ significantly. Adjusting for enteric pathogens and CD4 count, the hazard ratio (HR) for zinc supplementation and cessation of diarrhea (according to the diaries) was 0.91 (95% confidence interval [CI]: 0.50 to 1.64).\n Supplemental zinc had no significant effect on the duration or remission of diarrhea in HIV-infected adults.", "Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain.\n We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months.\n Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load.\n Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania.", "Vitamin A administered to children infected with the human immunodeficiency virus before influenza vaccination in a double-blind randomized study did not enhance vaccine serologic responses but did dampen the increase in the human immunodeficiency virus viral load 14 days after immunization (vitamin A, decrease of 0.13 +/- 0.09 log(10) copies/mL; placebo, increase of 0.14 +/- 0.08, P =.02).", "To examine the immunologic, metabolic, and clinical effects of broad spectrum micronutrient supplementation in HIV-infected patients taking highly active antiretroviral therapy (HAART).\n A prospective, randomized, double-blinded, placebo-controlled trial.\n Forty HIV-infected patients taking a stavudine and/or didanosine-based HAART regimen were prospectively randomized to receive micronutrients or placebo twice daily for 12 weeks. Data were collected at 4-week intervals including immunologic, metabolic, and clinical measurements. The study examined the effect of micronutrient supplementation on immunologic parameters as the primary end point. The secondary end points were metabolic and clinical effects and distal symmetrical polyneuropathy.\n The mean absolute CD4 count increased by an average of 65 cells in the micronutrient group versus a 6-cell decline in the placebo group at 12 weeks (P = 0.029). The absolute CD4 count increased by an average of 24% in the micronutrient group versus a 0% change in the placebo group (P = 0.01). The mean HIV-1 RNA decreased in the micronutrient supplementation group, although not significantly. Neuropathy scores improved in the micronutrient group by 42% compared with a 33% improvement in the placebo arm. This difference did not reach statistical significance. Fasting serum glucose, insulin, and lipids were not adversely affected in the patients taking the micronutrients.\n Micronutrient supplementation can significantly improve CD4 cell count reconstitution in HIV-infected patients taking HAART. The micronutrient supplement tested was well tolerated and may hold promise as an adjuvant therapy in the treatment of HIV. Further investigation is warranted.", "Malnutrition is common in pulmonary tuberculosis (TB), and may impair survival. The objective of this study was to assess effects of multi-vitamin/mineral (MVM) and zinc (Zn) supplementation during TB treatment on mortality. Patients diagnosed with sputum-positive pulmonary TB in Mwanza, Tanzania, were randomised, using a two-by-two factorial design, to Zn (45 mg) or placebo, and MVM (vitamins A, B, C, D, E, and selenium and copper) or placebo. Survival status was ascertained at the end of the 8-month TB treatment and supplementation period. Of 499 TB patients, 213 (43 %) had HIV. The mean weight gain at 7 months was 6.88 kg (95 % CI 6.36, 7.41). Zn and MVM combined, but neither alone (interaction, P=0.03), increased weight gain by 2.37 kg (95 % CI 0.91, 3.83), irrespective of HIV status. Survival status at 8 months was determined for 422 patients (84.6 %), of which fifty-two (12.3 %) had died. Among fifty-two deaths, there were no effects of MVM (relative risk (RR) 0.73; 95 % CI 0.43, 1.23) and Zn (RR 0.76; 95 % CI 0.46, 1.28). However, among HIV co-infected patients, marginally significant effects of both MVM (RR 0.60; 95 % CI 0.34, 1.05) and Zn (RR 0.63, 95 % CI 0.37, 1.08) were seen, and MVM and Zn combined reduced mortality (RR 0.29; 95 % CI 0.10, 0.80; interaction ratio 0.52). In conclusion, supplementation with MVM, including Zn, during treatment of pulmonary TB may reduce mortality in those co-infected with HIV. A randomised trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding.", "Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis.\n To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality.\n We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment.\n The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2.\n Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).", "Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence.\n We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol.\n The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001).\n Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea.\n Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.", "To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children.\n Randomized, double blind, placebo-controlled trial.\n Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1).\n Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01).\n Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.", "In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women.\n In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat.\n 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts.\n Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.", "To evaluate the impact of selenium chemoprevention (200 microg/day) on hospitalizations in HIV-positive individuals.\n Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial.\n At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p <.05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p =.002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p =.01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p =.001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p =.001).\n Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1-infected patients.", "Despite findings that selenium supplementation may improve immune functioning, definitive evidence of its impact on human immunodeficiency virus (HIV) disease severity is lacking.\n High selenium yeast supplementation (200 mug/d) was evaluated in a double-blind, randomized, placebo-controlled trial. Intention-to-treat analyses assessed the effect on HIV-1 viral load and CD4 count after 9 months of treatment. Unless otherwise indicated, values are presented as mean +/- SD.\n Of the 450 HIV-1-seropositive men and women who underwent screening, 262 initiated treatment and 174 completed the 9-month follow-up assessment. Mean adherence to study treatment was good (73.0% +/- 24.7%) with no related adverse events. The intention-to-treat analyses indicated that the mean change (Delta) in serum selenium concentration increased significantly in the selenium-treated group and not the placebo-treated group (Delta = 32.2 +/- 24.5 vs 0.5 +/- 8.8 microg/L; P<.001), and greater levels predicted decreased HIV-1 viral load (P<.02), which predicted increased CD4 count (P<.04). Findings remained significant after covarying age, sex, ethnicity, income, education, current and past cocaine and other drug use, HIV symptom classification, antiretroviral medication regimen and adherence, time since HIV diagnosis, and hepatitis C virus coinfection. Follow-up analyses evaluating treatment effectiveness indicated that the nonresponding selenium-treated subjects whose serum selenium change was less than or equal to 26.1 microg/L displayed poor treatment adherence (56.8% +/- 29.8%), HIV-1 viral load elevation (Delta = +0.29 +/- 1.1 log(10) units), and decreased CD4 count (Delta = -25.8 +/- 147.4 cells/microL). In contrast, selenium-treated subjects whose serum selenium increase was greater than 26.1 microg/L evidenced excellent treatment adherence (86.2% +/- 13.0%), no change in HIV-1 viral load (Delta = -0.04 +/- 0.7 log(10) units), and an increase in CD4 count (Delta = +27.9 +/- 150.2 cells/microL).\n Daily selenium supplementation can suppress the progression of HIV-1 viral burden and provide indirect improvement of CD4 count. The results support the use of selenium as a simple, inexpensive, and safe adjunct therapy in HIV spectrum disease. Trial Registration isrctn.org Identifier: ISRCTN22553118." ]

[ "15992199", "16014595" ]

[ "A quality improvement intervention to increase palliative care in nursing homes.", "Improving the use of hospice services in nursing homes: a randomized controlled trial." ]

[ "Death is common in nursing homes, but access to palliative care is limited.\n To test whether a quality improvement (QI) intervention in nursing homes increases hospice, pain management, and advance care planning.\n The QI intervention was tested in seven nursing homes using a prepoststudy design. Two additional nursing homes served as control sites.\n Nine nursing homes serving 1169 residents.\n The intervention included recruitment and training of Palliative Care Leadership Teams in each facility, followed by six technical assistance meetings for team members. Hospice providers delivered six educational sessions for all nursing home staff using a structured curriculum. Teams received feedback of performance data on hospice enrollment, pain management, and advance care planning at 0, 3, and 6 months.\n Percentage of residents receiving hospice or palliative services, pain assessment, pain treatment among residents in pain, and documented advance care planning discussions.\n Intervention facilities increased hospice enrollment from 4.0% of residents at baseline to 6.8% postintervention (p = .01) and increased pain assessments from 18% to 60% (p < .001). Among resident in pain, orders for nonpharmacologic pain treatments increased from 15% to 35% (p < .001), but pain medication use did not change. Residents with in-depth discussions about end-of-life care increased from 4% to 17% (p < .001). There were no significant changes in control sites.\n A quality improvement intervention was effective in increasing hospice enrollment, pain assessment, nonpharmacologic pain treatment, and advance care planning discussions.", "Hospice care may improve the quality of end-of-life care for nursing home residents, but hospice is underutilized by this population, at least in part because physicians are not aware of their patients' preferences.\n To determine whether it is possible to increase hospice utilization and improve the quality of end-of-life care by identifying residents whose goals and preferences are consistent with hospice care.\n Randomized controlled trial (December 2003-December 2004) of nursing home residents and their surrogate decision makers (N=205) in 3 US nursing homes.\n A structured interview identified residents whose goals for care, treatment preferences, and palliative care needs made them appropriate for hospice care. These residents' physicians were notified and asked to authorize a hospice informational visit.\n The primary outcome measures were (1) hospice enrollment within 30 days of the intervention and (2) families' ratings of the quality of care for residents who died during the 6-month follow-up period.\n Of the 205 residents in the study sample, 107 were randomly assigned to receive the intervention, and 98 received usual care. Intervention residents were more likely than usual care residents to enroll in hospice within 30 days (21/107 [20%] vs 1/98 [1%]; P<.001 [Fisher exact test]) and to enroll in hospice during the follow-up period (27/207 [25%] vs 6/98 [6%]; P<.001). Intervention residents had fewer acute care admissions (mean: 0.28 vs 0.49; P = .04 [Wilcoxon rank sum test]) and spent fewer days in an acute care setting (mean: 1.2 vs 3.0; P = .03 [Wilcoxon rank sum test]). Families of intervention residents rated the resident's care more highly than did families of usual care residents (mean on a scale of 1-5: 4.1 vs 2.5; P = .04 [Wilcoxon rank sum test]).\n A simple communication intervention can increase rates of hospice referrals and families' ratings of end-of-life care and may also decrease utilization of acute care resources." ]

[ "20335449", "21948120", "19747869", "22183208", "20357374" ]

[ "Exercise training in pregnancy reduces offspring size without changes in maternal insulin sensitivity.", "Exercise during pregnancy improves maternal glucose screen at 24-28 weeks: a randomised controlled trial.", "Supervised home-based exercise may attenuate the decline of glucose tolerance in obese pregnant women.", "Regular exercise during pregnancy to prevent gestational diabetes: a randomized controlled trial.", "Prevention of gestational diabetes: feasibility issues for an exercise intervention in obese pregnant women." ]

[ "Epidemiological studies have identified the importance of the in utero environment in providing a healthy start to life. Previous studies have suggested that the maternal environment, in particular a reduction in maternal insulin sensitivity, contributes significantly to fetal growth. Regular aerobic exercise, through an effect on maternal insulin sensitivity, may influence offspring size by regulating nutrient supply to the fetus.\n The aim of the study was to determine the effects of aerobic exercise training in the second half of pregnancy on maternal insulin sensitivity and neonatal outcomes.\n We conducted a community-based, randomized, controlled trial of exercise in pregnancy.\n Eighty-four healthy nulliparous women (mean +/- sd, age, 30 +/- 4 yr; body mass index, 25.5 +/- 4 kg/m(2)) participated in the study.\n Subjects participated in a home-based stationary cycling program from 20 wk gestation to delivery.\n Maternal insulin sensitivity, neonatal auxology, body composition, and growth-related peptides in cord blood were measured.\n Offspring of exercisers had lower birth weight (sd score, control, 0.23 +/- 0.8; exercise, -0.19 +/- 0.9; P = 0.03) and body mass index at birth (sd score, control, 0.40 +/- 0.9; exercise, -0.01 +/- 0.09; P = 0.04). The reduction in maternal insulin sensitivity in late gestation was not affected by exercise (P = 0.45) and was unrelated to offspring size. Exercise offspring had lower cord serum IGF-I (P = 0.03) and IGF-II (P = 0.04).\n Regular exercise was associated with lower birth weights and reduced cord concentrations of growth-related peptides, suggesting an influence of exercise on endocrine regulation of fetal growth. These effects on offspring growth were not associated with an exercise training effect on maternal insulin sensitivity.", "The influence of an exercise programme performed by healthy pregnant women on maternal glucose tolerance was studied.\n A physical activity (PA, land/aquatic activities) programme during the entire pregnancy (three sessions per week) was conducted by a qualified instructor. 83 healthy pregnant women were randomly assigned to either an exercise group (EG, n=40) or a control (CG, n=43) group. 50 g maternal glucose screen (MGS), maternal weight gain and several pregnancy outcomes were recorded.\n Significant differences were found between study groups on the 50 g MGS. Values corresponding to the EG (103.8 ± 20.4 mg/dl) were better than those of the CG (126.9 ± 29.5 mg/dl), p=0.000. In addition, no differences in maternal weight gain and no cases of gestational diabetes in EG versus 3 in CG (7%) (p>0.05) were found.\n A moderate PA programme performed during pregnancy improves levels of maternal glucose tolerance.", "The significant deterioration of insulin sensitivity and glucose tolerance during pregnancy can have serious health implications for both the pregnant woman and her baby. Although it is well established that regular exercise benefits insulin sensitivity in the nonpregnant population, the effect on glucose tolerance in obese pregnant women is not known. The purpose of this study was to investigate the effect of a supervised 10-week, home-based, exercise programme, beginning at week 18 of gestation, on glucose tolerance and aerobic fitness in previously sedentary obese women.\n Twelve sedentary obese women were randomized into an exercise (EX; n=6) or control (CON; n=6) group at 18 weeks of gestation. Those randomized to EX engaged in 10 weeks of supervised home-based exercise (three sessions a week of stationary cycling), while those in the CON group maintained their usual daily activity. Their glucose and insulin responses to an oral glucose tolerance test (OGTT), as well as their aerobic fitness, were assessed both pre- and postintervention.\n Reduced glucose tolerance in the CON, but not EX, group was indicated by a tendency postintervention towards higher blood glucose levels at 1h of the OGTT (P=0.072). Furthermore, at 2h of the postintervention OGTT, blood glucose tended to remain elevated from baseline in the CON (P=0.077). There was also a trend towards increased fitness in the EX (P=0.064), but not the CON group.\n Regular aerobic exercise begun during pregnancy may have favourable effects on glucose tolerance and fitness in obese women, and warrants further investigation in a larger sample population.", "To assess whether exercise during pregnancy can prevent gestational diabetes and improve insulin resistance.\n A total of 855 women in gestational week 18-22 were randomly assigned to receiving a 12-week standard exercise program (intervention group) or standard antenatal care (control group). The exercise program followed standard recommendations and included moderate-intensity to high-intensity activity 3 or more days per week. Primary outcomes were gestational diabetes and insulin resistance estimated by the homeostasis model assessment method. For the power calculation, we assumed a gestational diabetes prevalence of 9% in the control group and a prevalence of 4% in the exercise group (risk difference of 5%). Under these assumptions, a two-sample comparison with a 5% level of significance and power of 0.80 gave a study population of 381 patients in each group.\n At 32-36 weeks of gestation there were no differences between groups in prevalence of gestational diabetes: 25 of 375 (7%) in the intervention group compared with 18 of 327 (6%) in the control group (P=.52). There were no differences in insulin resistance between groups when adjusting for baseline values. Only 55% of women in the intervention group managed to follow the recommended exercise protocol. No serious adverse events related to physical exercise were seen, and the outcomes of pregnancy were similar in the two groups.\n There was no evidence that offering women a 12-week standard exercise program during the second half of pregnancy prevents gestational diabetes or improves insulin resistance in healthy pregnant women with normal body mass indexes.\n : ClinicalTrials.gov, www.clinicaltrials.gov, NCT00476567.", "To examine the feasibility of an individualized exercise program to prevent gestational diabetes mellitus (GDM) in obese pregnant women.\n The study was a pilot randomized controlled trial with obese pregnant women (intervention group, individualized exercise program [n = 25]; control group, usual care [n = 25]). Average weekly energy expenditure (MET hours per week and kilocalories per week) of exercise-specific activity was assessed during pregnancy using the Pregnancy Physical Activity Questionnaire. Fasting glucose and insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at baseline and 20, 28, and 36 weeks' gestation.\n Of the women in the intervention group, 16 of 22 (73%) achieved more than 900 kcal/week of exercise-based activity at 28 weeks compared with 8 of 19 women in the control group (42%), P = 0.047. However, insulin resistance (HOMA-IR) did not differ between the groups.\n This intervention was feasible and prompted a modest increase in physical activity. However, we are not confident that this intervention would be sufficient to prevent GDM." ]

[ "3534202", "1080560", "7030228" ]

[ "Randomized clinical trial of an oscillating air mattress in preterm infants: effect on apnea, growth, and development.", "Effects of waterbed flotation on premature infants: A pilot study.", "A controlled trial of a regularly cycled oscillating waterbed and a non-oscillating waterbed in the prevention of apnoea in the preterm infant." ]

[ "To investigate claims that oscillating mattresses reduce apnea of prematurity and improve growth and neurobehavioural development, we performed a randomized clinical trial using a predetermined sample size. Preterm infants weighing from 750 to 1750 gm at birth were randomly assigned, by 250 gm strata, to either a conventional mattress (n = 63) or to an air mattress (n = 59) oscillating at 14 to 16 regular pulses per minute. Infants remained on the oscillating air mattress for at least 7 days or until 34 weeks postmenstrual age. Apneic episodes occurred and required treatment equally in the two groups; this lack of an effect was seen for both sexes and all weight groups. Both weight and energy intake were similar. Neurobehavioral development as shown by sleep state, habituation testing, and behavioral assessment at term, 3, 6, and 12 months was similar in the two groups. There was no difference in the incidence of neurologic abnormalities. We conclude that an oscillating air mattress has no prophylactic value in reducing apnea and does not enhance growth and development.", "Two types of waterbeds were developed to impart compensatory vestibular-proprioceptive stimulation to premature infants. Twenty-one infants ranging in gestational age from 27 to 34 weeks and birthweights from 1,050 to 1,920 gm were included in this pilot study. Assignment to experimental and control groups was made by random design. The experimental group consisted of ten infants who were placed on a gently oscillating waterbed before the sixth postnatal day, where they remained for seven days. Their clinical progress was compared with that of a control group of 11 similar babies. Waterbed flotation was found to be a safe procedure; there was no significant effects on the infants' vital signs, weight, or frequency of emesis. Highly significant differences were found in the incidence of apnea between the two groups, with infants on the oscillating waterbed having significantly fewer apneic spells. Infants placed on the waterbed during the first four postnatal days benefited more than those placed later. A non-oscillating waterbed was found clinically useful for very small prematures with severe skin problems, for infants recovering from abdominal surgery, and for infants receiving parenteral nutrition.", "Fourteen preterm infants spent a mean of 23 hours divided into 4-hour periods with and without regular oscillations, 10 infants also being studied for control periods, before and afterwards. Electrocardiogram and impedance pneumogram were recorded continuously and analysed blindly. The waterbed, with or without oscillations, had no effect on apnoea or bradycardia when compared with control periods. Infants had appreciably more episodes of severe bradycardia while on the oscillating than on the non-oscillating waterbed." ]

[ "2496815", "1457626", "9844753", "10484950", "8513037", "11083131" ]

[ "Effect of melatonin on jet lag after long haul flights.", "Melatonin and jet lag: confirmatory result using a simplified protocol.", "Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag.", "Jet lag: clinical features, validation of a new syndrome-specific scale, and lack of response to melatonin in a randomized, double-blind trial.", "A double-blind trial of melatonin as a treatment for jet lag in international cabin crew.", "Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones." ]

[ "To determine whether doses of the pineal hormone melatonin alleviate jet lag.\n Double blind, placebo controlled crossover trial.\n Long haul return flights from Auckland, New Zealand, to London and back.\n Twenty volunteers with experience of transcontinental flights (eight women and 12 men aged 28 to 68).\n Melatonin (or placebo) 5 mg three days before flight, during flight, and once a day for three days after arrival.\n Symptoms of jet lag.\n Visual analogue scale for feelings of jet lag and tiredness; profile of moods states questionnaire for vigour-activity and fatigue-inertia; and retrospective ratings 10 days after arrival of sleep pattern, energy, and daytime tiredness. Feelings of jet lag were less for subjects taking melatonin (mean score 2.15 v 3.4); these subjects took fewer days than the placebo group to establish a normal sleep pattern (2.85 v 4.15), to not feel tired during the day (3.0 v 4.6), and to reach normal energy levels (3.25 v 4.7). Results for fatigue-inertia and vigour-activity were similar. For all subjects jet lag was more severe on the return (westward) than the outward (eastward) journey.\n Melatonin can alleviate jet lag and tiredness after long haul flights.", "This study replicates the alleviation of jet-lag with melatonin in a simplified protocol for eastward flight. At 22-n hr (n is the time-lag between the North American departure point and France), subjects took either melatonin (8 mg, n = 15), or placebo (n = 15) on the day of the return flight and for 3 consecutive days. On day 8, self-ratings significantly discriminated between melatonin and placebo for global treatment efficacy, morning fatigue, and evening sleepiness.", "To compare the impact of various dosage forms of melatonin and placebo on jet lag symptoms, 320 volunteers who had flights over 6 to 8 time zones were recruited for a double-blind, randomized, placebo-controlled study. The volunteers received either melatonin 0.5-mg fast-release (FR) formulation, melatonin 5-mg FR formulation, melatonin 2-mg controlled-release (CR) formulation, or placebo. The study medication was taken once daily at bedtime during 4 days after an eastward flight. The volunteers completed the Profile of Mood States (POMS), sleep log, and symptoms questionnaires once daily and the Karolinska Sleepiness Scale (KSS) three times daily prior to departure and during the 4 days of medication intake postflight. A total of 234 (73.1%) participants were compliant and completed the study. The FR melatonin formulations were more effective than the slow-release formulation. The 5-mg FR formulation significantly improved the self-rated sleep quality (p < .05), shortened sleep latency (p < .05), and reduced fatigue and daytime sleepiness (p < .05) after intercontinental flight. The lower physiological dose of 0.5 mg was almost as effective as the pharmacological dose of 5.0 mg. Only the hypnotic properties of melatonin, sleep quality and sleep latency, were significantly greater with the 5.0-mg dose.", "The goals of this study were to validate a new rating scale for measuring severity of jet lag and to compare the efficacy of contrasting melatonin regimens to alleviate jet lag.\n This was a randomized, double-blind trial of placebo and three alternative regimens of melatonin (5.0 mg at bedtime, 0.5 mg at bedtime, and 0.5 mg taken on a shifting schedule) for jet lag. The subjects were 257 Norwegian physicians who had visited New York for 5 days. Jet lag ratings were made on the day of travel from New York back to Oslo (6 hours eastward) and for the next 6 days in Norway. The main outcome measures were scale and item scores from a new, syndrome-specific instrument, the Columbia Jet Lag Scale, that identifies prominent daytime symptoms of jet lag distress.\n There was a marked increase in total jet lag score in all four treatment groups on the first day at home, followed by progressive improvement over the next 5 days. However, there were no significant group differences or group-by-time interactions. In addition, there was no group effect for sleep onset, time of awakening, hours slept, or hours napping. Ratings on a summary jet lag item were highly correlated with total jet lag scores (from a low of r = 0.54 on the day of travel to a high of r = 0.80 on day 3). The internal consistency of the total jet lag score was high on each day of the study.\n The use of melatonin for preventing jet lag needs further study.", "This study investigated the efficacy of oral melatonin in alleviating jet lag in flight crew after a series of international flights. The optimal time for taking melatonin in this group was also investigated. In a double-blind placebo-controlled trial, 52 international cabin crew were randomly assigned to three groups; early melatonin (5 mg started 3 days prior to arrival until 5 days after return home); late melatonin (placebo for 3 days then 5 mg melatonin for 5 days); and placebo. Daily ratings showed a trend in jet lag, mood, and sleepiness measures toward an improved recovery in the late melatonin group and a worse recovery in the early melatonin group as compared to placebo. Retrospective ratings made 6 days after arrival showed the late melatonin group reported significantly less jet lag and sleep disturbance following the flight compared to placebo. The late melatonin group also showed a significantly faster recovery of energy and alertness than the early melatonin group, which reported a worse overall recovery than placebo. These findings show melatonin may have potential benefits for international aircrew.", "Subjective, physiological and physical performance variables are affected following travel across multiple time-zones (jet-lag). The objective of the study was to examine the effects of oral melatonin in alleviating jet-lag by investigating its effects on subjects who had flown from London to Eastern Australia, 10 time-zones to the east. Melatonin (5 mg day(-1)) or placebo capsules were administered to 14 experimental (13 males and 1 female) and 17 control subjects (15 males and 2 females), respectively, in a double-blind study; the time of administration was in accord with the current consensus for maximizing its hypnotic effect. Grip strength and intra-aural temperature were measured on alternate days after arrival at the destination, at four different times of day (between the times 07:00 - 08:00 h, 12:00 - 13:00 h, 16:00 - 17:00 h and 19:00 - 20:00 h local time). In addition, for the first 6 - 7 days after arrival in Australia, subjective ratings of jet-lag on a 0 - 10 visual analogue scale and responses to a Jet-lag Questionnaire (incorporating items for tiredness. sleep, meal satisfaction and ability to concentrate) were recorded at the above times and also on retiring (at about midnight). Subjects continued normally with their work schedules between the data collection times. Subjects with complete data (13 melatonin and 13 placebo subjects), in comparison with published data, showed partial adjustment of the diurnal rhythm in intra-aural temperature after 6 days. A time-of-day effect was evident in both right and left grip strength during adjustment to Australian time; there was no difference between the group taking melatonin and that using the placebo. Right and left grip strength profiles on day 6 were adjusted either by advancing or delaying the profiles, independent of whether subjects were taking melatonin or placebo tablets. Subjects reported disturbances with most measures in the Jet-lag Questionnaire but, whereas poorer concentration and some negative effects upon sleep had disappeared after 3 - 5 days, ratings of jet-lag and tiredness had not returned to 'zero' (or normal values), respectively, by the sixth day of the study. Subjects taking melatonin showed no significant differences from the placebo group in perceived irritability, concentration, meal satisfaction, ease in getting to sleep and staying asleep, frequency of bowel motion and consistency of the faeces. These results suggest that, in subjects who, after arrival, followed a busy schedule which resulted in frequent and erratic exposure to daylight, melatonin had no benefit in alleviating jet-lag or the components of jet-lag, and it did not influence the process of phase adjustment." ]

[ "6393805", "16173138", "18218147", "1443440" ]

[ "A double-blind, placebo-controlled trial of magnesium sulfate in the ethanol withdrawal syndrome.", "Magnesium supplementation and muscle function in patients with alcoholic liver disease: a randomized, placebo-controlled trial.", "Magnesium treatment in alcoholics: a randomized clinical trial.", "Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics." ]

[ "One hundred alcoholics treated for ethanol withdrawal were assigned randomly according to a double-blind protocol to receive four intramuscular injections of 2 g of magnesium sulfate at 6-hr intervals or an equivalent amount of normal saline. All patients were treated for signs of withdrawal according to a standardized protocol using orally-administered chlordiazepoxide for sedation. Three observers rated each patient for signs of withdrawal. There was no statistically significant difference between magnesium sulfate and placebo groups on any of the variables measured. The groups required equivalent amounts of chlordiazepoxide for control of withdrawal. The authors concluded that the routine administration of magnesium sulfate is not indicated for the management of alcohol withdrawal unless accompanied by cardiac arrhythmias.", "The study was undertaken in order to evaluate the effect of magnesium (Mg) supplementation on muscle contents of Mg, muscle strength, muscle mass and sodium, potassium pumps (Na,K-pumps) in patients with alcoholic liver disease. Retrospectively, patients were also stratified according to spironolactone treatment.\n The study comprised a placebo-controlled, randomized trial in which 59 consecutive patients with alcoholic liver disease were treated with Mg intravenously and orally (12.5 mmol daily) or placebo for 6 weeks. Muscle content of Mg, maximum isokinetic muscle strength, skeletal muscle mass and muscle content of Na,K-pumps were measured before and after Mg supplementation.\n Muscle Mg did not increase during the trial (paired t-test), but Mg supplementation and the duration of pre-study spironolactone treatment were independent predictors of muscle Mg (multiple regression). Muscle strength increased by 14% during the trial (p<0.001) and muscle mass increased by 11% (p=0.05), but with no difference between placebo and Mg treatment. Spironolactone treatment was associated with a 33% increase in the content of Na,K-pumps (p<0.001).\n Six weeks of Mg supplementation did not increase muscle Mg, although Mg supplementation and spironolactone treatment were independent predictors of muscle Mg. The intervention had no effect on muscle strength and mass, but both increased during the study, probably owing to the general care and attendance to the patients.", "Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak.\n The effect of Mg was studied in a randomized, parallel group, double-blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (S-AST) and alanine-aminotransferase (S-ALT) activity.\n The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df = 53, p = 0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df = 49, p = 0.045).\n Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease.\n ClinicalTrials.gov ID NCT00325299.", "Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics." ]

[ "3513150", "8040418", "9620490", "12785025", "17626987", "16490980", "2462473", "2669345", "387047", "2547245", "3542001", "3528240", "6344906", "3926169", "2466712", "12011525", "6167979" ]

[ "Cadexomer iodine in the management of venous leg ulcers in general practice.", "Comparison of ciprofloxacin or trimethoprim therapy for venous leg ulcers: results of a pilot study.", "The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Cadexomer Iodine Study Group.", "Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospective-randomized-controlled study.", "Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide: evaluation with a microcirculatory model, including free radicals, laser doppler flux, and PO2/PCO2 measurements.", "Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy.", "Comparison of cadexomer iodine and dextranomer for chronic venous ulcers.", "Multicenter trial of cadexomer iodine to treat venous stasis ulcer.", "Levamisole treatment in ulcus cruris. A double-blind placebo-controlled study.", "A comparative study of ciprofloxacin and conventional therapy in the treatment of patients with chronic lower leg ulcers infected with Pseudomonas aeruginosa or other gram-negative rods.", "A study of the effect of cadexomer iodine in the treatment of venous leg ulcers.", "Systemic administration of antibiotics in the management of venous ulcers. A randomized clinical trial.", "A randomized trial comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers.", "Controlled trial of Iodosorb in chronic venous ulcers.", "In-patient treatment of chronic varicose venous ulcers. A randomized trial of cadexomer iodine versus standard dressings.", "The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: a proof-of-concept study.", "The treatment of varicose stasis ulcers: a controlled trail." ]

[ "nan", "nan", "The aim was to examine cadexomer iodine paste in a comparative clinical trial.\n A 12-week, randomized, open, controlled, multicenter, multinational trial in patients with exudating, venous leg ulcers of cadexomer iodine paste (Iodosorb/Iodoflex), hydrocolloid dressing (Duoderm E, Granuflex E), or paraffin gauze dressing (Jelonet) was carried out. All patients used short-stretch compression bandages (Comprilan) throughout the study. The primary efficacy variable was a reduction in ulcer size (%), and the secondary end-point was the time taken to stop exudation, when the patient had completed the study according to the protocol. A total of 153 patients entered the study and were treated for 12 weeks or until cessation of exudation.\n The mean reduction in ulcer size in all patients was 62% with cadexomer iodine vs. 41% and 24% for hydrocolloid and paraffin gauze (ns). Of those treated for 12 weeks (n = 51), ulcer area reduction was 66% for cadexomer iodine and 18% for hydrocolloid (p = 0.0127). For the whole material, the rate of healing (ulcer area reduction per week) was significantly higher for cadexomer iodine than for paraffin gauze (0.64 cm2/week vs. 0.19 cm2/week, p = 0.0353). The treatment costs were similar in all groups; however, when the costs were correlated with healing over a 12-week period, cadexomer iodine paste was found to be more cost effective than hydrocolloid dressing or paraffin gauze dressing.\n This study shows that cadexomer iodine paste is an efficient, cost-effective and safe alternative to hydrocolloid dressing and paraffin gauze dressing for the treatment of venous leg ulcers.", "In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p<0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing.", "In 32 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of the local application of a hydrogen peroxide cream (Crystacide) applied onto the skin was evaluated using a complex, proportional, microcirculatory model to assess and quantify venous microangiopathy after local treatment. A comparative group treated without Crystacide was included. Laser Doppler flowmetry was used to assess skin perfusion (flux and venoarteriolar response) in association with transcutaneous PO2 and PCO2 measurements. Local plasma free radicals were evaluated in the area surrounding the venous ulcer using the D-Roms test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatments. PO2 was increased (improved, P < .05), and plasma free radicals, PCO2, and laser Doppler flowmetry were decreased (improving toward normal values, P < .05). Also, the ulcerated area was significantly smaller at 10 days in the Crystacide group in comparison with controls (P < .05). In the proportional microcirculatory model, all parameters indicated an important level of improvement significantly larger than in controls. In conclusion, in chronic venous insufficiency and venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals, thus improving healing.", "The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema.\n To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers.\n 63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection.\n Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%).\n Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas).", "nan", "In a crossover study designed to judge the efficacy of the topical polymeric starch iodophore, cadexomer iodine, in accelerating the healing of venous stasis ulcers, 75 patients were prospectively randomly assigned to receive either cadexomer iodine or standard treatment. The control treatment consisted of a standard saline wet-to-dry compressive dressing. The patients improved with either treatment: ulcers healed more than twice as rapidly using cadexomer iodine (n = 38) as with standard therapy (n = 37) (P = .0025). Ulcers treated with cadexomer iodine showed trends toward less pain, exudate, pus, and debris, and a more rapid development of granulation tissue. Twelve patients crossed over from control treatment to the use of cadexomer iodine because of a failure to heal, but no patients switched to control therapy from the use of cadexomer iodine (P = .01). Except for occasional mild local burning in wounds treated with cadexomer iodine, no adverse effects were noted with either regimen.", "59 outpatients (27-82 years) with a chronic leg ulcer participated in a 20-week double-blind placebo-controlled trial of levamisole (levamisole 30; placebo 29). They were instructed to take a body weight adjusted number of tablets (2-5) for two consecutive days every week. Previously used topical treatment was kept unchanged. Control examinations were done every two weeks. Double-blind treatment was stopped because of evident failure after a median duration of 8 weeks in 2 levamisole and 8 placebo patients. The percentage of cured patients became significantly superior in the levamisole group from week 8 onwards, so that, by the end of the study, all levamisole patients were cured against only 76% of the controls. Three levamisole patients reported moderate gastric complaints.", "Twenty-six elderly patients with chronic leg ulcers infected by Pseudomonas aeruginosa or other aerobic Gram-negative rods were randomised to two treatment groups. The control group (eight patients) received conventional local therapy and the other group (18 patients) was treated with oral ciprofloxacin for three months in addition to conventional local therapy. In the beginning of the study both groups were comparable with the age of the patients and the associated diseases including impairment of arterial and venous circulation in the lower legs. Also the size, duration and the severity of the inflammation reaction in the leg ulcers were comparable before the start of the therapy. Ciprofloxacin was clinically more effective than the standard therapy in reducing the size of the ulcer (p less than 0.05). Also the need of extra systemic antibiotics decreased significantly in the ciprofloxacin group compared with the controls. In three out of eighteen ciprofloxacin treated patients the leg ulcers disappeared completely during the three months' study period compared with none in the control group. However, ciprofloxacin resistant strains, mainly staphylococci, appeared in the leg ulcers in 67% of the ciprofloxacin treated patients compared with 0% in the control group (p less than 0.01). No significant side-effects due to ciprofloxacin except the resistant strains were noticed. We conclude that oral long-term ciprofloxacin therapy is effective in the treatment of chronic leg ulcer infections due to Gram-negative rods but selection of ciprofloxacin resistant strains is a problem in this patient group.", "nan", "Forty-seven patients with chronic venous leg ulcers were included in a randomized clinical trial to evaluate the efficacy of systemically administered antibiotics in healing with condition. One group was treated by means of elastic support bandages only, whereas the other one received the same local treatment plus systemic antibiotics. No statistically relevant difference was noted between the two groups in healing rates of ulcers or in changes of the microbiologic flora. The results of our study do not support the routine administration of systemic antibiotics in the management of chronic venous leg ulcers.", "Ninety-three patients with treatment-resistant venous ulcers were included in a multicentre randomized trial to compare cadexomer iodine and the standard treatment used in each centre combined with compression bandages, in healing venous ulcers. The mean duration of ulcers before the trial was more than 2 years. With standard treatment the mean ulcer size increased slightly during the 6-week trial whereas with cadexomer iodine the ulcer size was significantly reduced. Cadexomer iodine was more effective than standard treatment for reduction of pain, removal of pus and debris, removal of exudate, stimulation of granulation and reduction of surrounding erythema. Bacterial infection of ulcers increased or did not change during treatment with the standard therapy whereas cadexomer iodine significantly reduced infection with Staphylococcus aureus, Pseudomonas aeruginosa and other pathogenic organisms. A correlation was seen between the time taken to reduce or eliminate infection with Staphylococcus aureus and rate of ulcer healing. Four patients complained of transient pain in the ulcer after application of the cadexomer iodine. It is concluded that cadexomer iodine increased the rate of healing of infected chronic venous ulcers.", "Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.", "A total of 67 patients with treatment resistant chronic venous ulcers were admitted to hospital for 6 weeks of bed rest and daily dressings. The patients came from a rural area in Poland with poor socioeconomic conditions. They were randomized to treatment with either standard dressings or with cadexomer iodine. After 6 weeks all but four patients had shown a clear reduction of ulcer area; the mean reduction was 54% within the former group and 71% with cadexomer iodine. The latter treatment was significantly more effective than the standard hospital dressings in debriding the ulcer, accelerating healing and reducing pain. Elevation of serum concentrations of protein-bound iodine occurred after treatment with cadexomer iodine in patients with large ulcers, but tests of thyroid function showed no changes associated with the use of cadexomer iodine. It is concluded that cadexomer iodine significantly accelerates the healing of chronic, infected, treatment-resistant, venous ulcers in hospitalized patients.", "Some of the views contrasting the beneficial and toxic effects of antimicrobials upon wound healing remain controversial.\n To assess the clinical relevance of histological findings following antimicrobial applications on chronic leg ulcers.\n The present study was performed in three parallel groups of 17 patients suffering from at least 2 similar chronic leg ulcers. Clinical planimetric assessments were performed before and after 3 and 6 weeks of treatment using hydrocolloid dressings. In addition, 1 ulcer in each patient received applications of povidone-iodine (PVP-I), silver sulfadiazine or chlorhexidine digluconate. Histological examinations were made at inclusion and after the 6-week therapy. Time to healing was also recorded.\n At entry in the study, fibroblasts, macrophages, neutrophils and vessels were abundant in the ulcers. In addition, focal necrotizing vasculitis was related to the microbiological load. Compared to the control lesions, both the healing rate and time to healing of the leg ulcers showed a modest improvement at the sites receiving silver sulfadiazine (2-7%) or chlorhexidine digluconate (-1 to 5%). By contrast, PVP-I increased significantly the healing rate (4-18%, p < 0.01), and time to healing was reduced by 2-9 weeks (p < 0.01). The 3 antimicrobials decreased the bacterial density, and the vascular margination and migration of inflammatory cells, thus abating the vasculitic changes. PVP-I applications did not alter the microvessels and did not significantly reduce the density in dendrocytes and fibroblasts. By contrast, both silver sulfadiazine and chorhexidine digluconate appeared to alter the superficial microsvasculature including the dendrocyte population.\n Although topical antimicrobials may apparently achieve almost similar activity on the bacterial load inside chronic leg ulcers, the toxicity upon host cells was different among these agents. PVP-I appeared to be an efficient compound in these respects exhibiting a positive and relevant clinical effect.\n Copyright 2002 S. Karger AG, Basel", "nan" ]

[ "6516811", "884446", "328108", "323443", "363995", "29088", "990784", "383023" ]

[ "Effects of naloxone on newborn infant behavior after maternal analgesia with pethidine during labor.", "Effects of naloxone on pethidine-induced neonatal depression. Part II--Intramuscular naloxone.", "Effects of naloxone on pethidine-induced neonatal depression. Part I--Intravenous naloxone.", "Use of nalotone to to reverse narcotic respiratory depression in the newborn infant.", "Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia.", "Clinical investigations of the influence of various naloxone doses on the newborn.", "Reversal of narcotic depression in the neonate by nalozone.", "Effects of pethidine and its antagonists on the newborn." ]

[ "Infants born to mothers receiving 100 mg of pethidine during labor, were randomly given either 100 micrograms of naloxone (n = 14) or 0.25 ml 0.9% NaCl (n = 13) one hour post partum. Infant behavior was assessed with the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) and the Broussard Neonatal Perception Inventory (NPI). No differences in cluster scores on the BNBAS were found between the two groups. Both groups improved scores over time in 4 out of 7 clusters. On the NPI, mothers assessed naloxone infants as having less optimal behavior than did the control mothers. The results of this study on the effects of naloxone on infant behavior and maternal perception of newborn behavior do not warrant administration of naloxone after maternal analgesia with pethidine in the absence of clinical evidence of respiratory depression in the newborn.", "Thirty full-term infants whose mothers had had pethidine during labour were given either naloxone 200 microgram or normal saline intramuscularly. The drugs were chosen blindly and administered within one minute of birth. Naloxone produced a significant reduction in mean alveolar carbon dioxide tension and an increase in carbon dioxide excretion and mean alveolar ventilation at all times up to 48 hours after birth. The mean rate of habituation to a repeated auditory stimulus, the mean sucking frequency, the sucking pressure, and the mean consumption of milk were all significantly higher in the naloxone-treated group than in the placebo-treated group up to 48 hours after birth. Intramuscular naxolone therefore seemed to reverse the undesirable effects of pethidine.", "Infants whose mothers had had pethidine during labour were given either naloxone 40 microgram or isotonic saline administered intravenously double-blind within one minute of birth. Peak alveolar carbon dioxide tension, carbon dioxide excretion, alveolar ventilation, feeding behaviour, and habituation to a specific sound stimulus were measured regularly up to 48 hours after birth. Alveolar carbon dioxide tension was significantly lower and alveolar ventilation significantly higher half an hour after birth in the naloxone-treated group than in the saline-treated group, but these differences between the groups were not significant at any other time, and there were no significant differences in sucking frequency or pressure, milk consumption, or habituation to the auditory stimulus.", "Twenty neonates whose mothers had received meperidine (1.0 to 1.5 mg/kg) intravenously within three hours of delivery were studied to determine the effectiveness of naloxone in reversing neonatal respiratory depression. The following measurements were carried out within 20 to 30 minutes after delivery: minute ventilation, end tidal CO2, and ventilatory response to CO2. These determinations were repeated after administration of either placebo or naloxone, 0.01 mg/kg intramuscularly. Minute ventilation and PAco were within a normal range before medication in both groups, but the slope of the CO2 response curve was decreased, indicating mild-to-moderate respiratory depression. After administration of placebo the test results did not change significantly. After administration of naloxone, VE increased significantly (P less than 0.05) and the slope of the CO2 response curve doubled (P less than 0.001). Naloxone effectively reverses narcotic depression of the respiratory center in the newborn infant.", "To investigate the presence of subtle narcotic depression following maternal narcotic analgesia, we have evaluated the effects of naloxone versus placebo in a double-blind parallel group study in 43 normal term newborn infants whose mothers had received routine narcotic analgesia within six hours prior to delivery. Infants were given either an intramuscular injection of 20 microgram/kg naloxone or 0.20 ml/kg placebo after determination of the one-minute Apgar score, and the following measurements were compared: Apgar scores at one and five minutes, capillary blood gas values at one, 60, 120, and 240 minutes, and neurobehavioral assessments at one, 4, and 24 hours. No adverse effects from naloxone were observed. Neither Apgar scores nor capillary blood gas determinations differed significantly between the two groups. Response to sound was significantly higher in the naloxone group at 24 hours. The alertness score was significantly higher for the naloxone group at one and four hours; the general assessment score for the naloxone group was significantly higher at four and 24 hours. Average scores of naloxone and placebo groups were also different at four and 24 hours of age. These data demonstrate that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status, potentially reversible by administration of naloxone shortly following delivery.", "nan", "Naloxone 40 mug was administered intravenously one minute after birth to 20 out of 44 neonates whose mother had been given pethidine in labour. These neonates were compared with 20 others whose mothers had had only lumbar epidural block. Alveolar PCO2, alveolar ventilation, and ventilatory rate were measured 10 and 30 minutes after birth. The untreated neonates of mothers who had had pethidine showed significant ventilatory depression compared with infants in the epidural and naloxone-treated groups. The naloxone-treated neonates were comparable with the epidural group, although the effects of naloxone were diminishing at 30 minutes. Naloxone is an effective narcotic antagonist which should be considered to be the drug of choice for treating narcotic depression in the neonate.", "Nalorphine and naloxone were compared as to their effectiveness as pethidine antagonists. 85 infants were divided into a control group containing 19 newborn babies whose mothers did not receive pethidine and the babies received no antagonist, and three groups in which the mothers all received pethidine and the babies had either no antagonist (24), nalorphine IV (16), or naloxone IV (26). All the babies were assessed by measuring their neurobehavioural states and respiratory functions. A further 12 newborn babies had naloxone plasma levels measured by radioimmunoassay. Although standard doses of nalorphine effectively antagonised the depressive effect on respiration induced by pethidine, there was a pronounced and undesirable excitatory agonist action. Naloxone was not observed to have any agonist activity, but the recommended IV dose (0.01 mg/kg) had only a slight and delayed antagonist action as measured by respiratory function tests. A more rapid and improved antagonism was noted after this dose was doubled (0.02 mg/kg). The plasma elimination-phase half-life of naloxone after intravenous cord injection was about 3 hours.20" ]

[ "16087029" ]

[ "Dexamethasone inner ear perfusion by intratympanic injection in unilateral Ménière's disease: a two-year prospective, placebo-controlled, double-blind, randomized trial." ]

[ "To investigate the efficacy of dexamethasone inner ear perfusion by intratympanic injection in hearing loss, tinnitus, aural fullness, and vertigo in the treatment of unilateral Ménière's disease and compare it with the control group.\n A prospective, randomized, double-blind study with 2-year follow-up comparing changes secondary to dexamethasone inner ear perfusion versus placebo consisting of saline solution.\n Twenty-two patients having definite Ménière's disease as outlined by the 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium. All the patients were older than 18 years of age and were not receiving any other form of treatment with steroids for their Ménière's disease.\n Five consecutive daily intratympanic injections of dexamethasone or placebo to the involved ear.\n In the dexamethasone group at 2-year follow-up, complete control of vertigo (class A) was achieved in 9 of 11 patients (82%) and substantial control of vertigo (class B) in the remaining 2 patients (18%.) In the control group only 7 of 11 patients (64%) finished the 2-year follow-up because in the other 4 patients (36%) we had to give another treatment for the continuing vertigo and thus they were classified as failure (class F.) From the 7 patients who have finished the follow-up of 2 years in the control group, 4 patients (57%) achieved class A, 2 patients (29%) achieved class C, and 1 patient (14%) class F.\n Dexamethasone (4 mg/mL) inner ear perfusion in a group of patients with unilateral Ménière's disease (Shea's stage III) showed 82% of complete control of vertigo over placebo (57%). There was also a subjective improvement in tinnitus (48%), hearing loss (35%), and aural fullness (48%) in the dexamethasone group compared with 20%, 10%, and 20% respectively in the control group." ]

[ "5823631", "9108851" ]

[ "Breath-holding attacks. The role of psychological factors and iron therapy.", "Effectiveness of iron therapy on breath-holding spells." ]

[ "nan", "The objective of this study is to investigate the effect of iron therapy on breath-holding spells (BHS).\n Sixty-seven children with BHS were enrolled in a clinical trial to evaluate the effect of iron therapy on BHS. At the beginning of therapy, the clinical, laboratory, and demographic characteristics of the patients in the treatment group (n = 33) and placebo group (n = 34) were comparable. Patients were assessed weekly for the first 8 weeks and then every 2 weeks for the next 8 weeks. Response to therapy was assessed by the change in the frequency of BHS.\n Children treated with iron showed significant reduction in the frequency of BHS (88%) compared with the frequency (6%) in the placebo group. As expected, the treated group showed a significant improvement of a number of blood indexes compared with the placebo group. Baseline mean levels of hemoglobin and total iron binding capacity were predictive of a favorable response to iron treatment.\n Results of this study indicate that iron therapy is effective in the treatment of BHS and that iron-deficient children seem to be more likely to benefit from such therapy. Response to iron therapy was strongly correlated with improvement in blood indexes." ]

[ "1355798", "2087879", "15845509", "8501336", "2807523", "9388905", "10823767", "7967990", "8296092", "12443672", "7822046", "10440439", "7668039", "1583321", "8359923", "19761838", "9615498", "19720365", "17055622", "3540139", "16996172", "16028125", "19819004", "8228350", "11895960", "3392421", "18523643", "10569747", "10674661", "10738097", "9207368", "9014909", "1398956", "8560536", "8605522", "9916056", "11884967" ]

[ "Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children.", "Randomized double-blind placebo controlled trial to evaluate the safety and immunogenicity of the live oral cholera vaccine strain CVD 103-HgR in Swiss adults.", "The vaccine candidate Vibrio cholerae 638 is protective against cholera in healthy volunteers.", "Safety and immunogenicity of the oral, whole cell/recombinant B subunit cholera vaccine in North American volunteers.", "Preliminary assessment of the safety and immunogenicity of live oral cholera vaccine strain CVD 103-HgR in healthy Thai adults.", "[Community trial for safety and immunogenicity of oral-administered lyophilized rBS-WC cholera vaccine].", "Two-year study of the protective efficacy of the oral whole cell plus recombinant B subunit cholera vaccine in Peru.", "Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits.", "[Tolerance and immunogenicity of an oral dose of CVD 103-HgR, a live attenuated Vibrio cholerae 01 strain: a double-blind study of Chilean adults].", "Calibrated serological techniques demonstrate significant different serum response rates to an oral killed cholera vaccine between Swedish and Nicaraguan children.", "Attenuated live cholera vaccine strain CVD 103-HgR elicits significantly higher serum vibriocidal antibody titers in persons of blood group O.", "Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers.", "Community-based assessment of safety and immunogenicity of the whole cell plus recombinant B subunit (WC/rBS) oral cholera vaccine in Peru.", "Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand.", "Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels.", "Immune responses following one and two doses of the reformulated, bivalent, killed, whole-cell, oral cholera vaccine among adults and children in Kolkata, India: a randomized, placebo-controlled trial.", "A single dose of live oral cholera vaccine CVD 103-HgR is safe and immunogenic in HIV-infected and HIV-noninfected adults in Mali.", "Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.", "Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults.", "B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity.", "Peru-15, a live attenuated oral cholera vaccine, is safe and immunogenic in Bangladeshi toddlers and infants.", "Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh.", "Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial.", "Safety, immunogenicity, and transmissibility of single-dose live oral cholera vaccine strain CVD 103-HgR in 24- to 59-month-old Indonesian children.", "Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine.", "Field trial of oral cholera vaccines in Bangladesh: results of one year of follow-up.", "A randomized, placebo-controlled trial of the bivalent killed, whole-cell, oral cholera vaccine in adults and children in a cholera endemic area in Kolkata, India.", "Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination.", "Safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit (WC/rCTB) cholera vaccine in Peruvian adults and children.", "Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area.", "Evaluation of Peru-15, a new live oral vaccine for cholera, in volunteers.", "Field trial of a locally produced, killed, oral cholera vaccine in Vietnam.", "Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial.", "Immunological response to Vibrio cholerae O1 infection and an oral cholera vaccine among Peruvians.", "Safety and immunogenicity of oral killed whole cell recombinant B subunit cholera vaccine in Barranquilla, Colombia.", "Preliminary assessment of the safety and immunogenicity of a new CTXPhi-negative, hemagglutinin/protease-defective El Tor strain as a cholera vaccine candidate.", "Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam." ]

[ "Oral vaccines offer great promise as public-health measures to prevent disease in less-developed countries. CVD 103-HgR, a genetically engineered, attenuated, Vibrio cholerae O1 strain has proved effective in industrialised countries. We have assessed the safety, immunogenicity, and excretion of this live cholera vaccine in children in north Jakarta, Indonesia. 412 children aged 5-9 years received single doses of 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9), or 1 x 10(10) colony forming units (CFU) of CVD 103-HgR or placebo (5 x 10(8) inactivated Escherichia coli K-12) with buffer. All doses were well tolerated. The 5 x 10(8) CFU dose, which is highly immunogenic in subjects in industrialised countries (greater than 90% seroconversion), elicited seroconversions of vibriocidal antibody in only 16% of Indonesian children. By contrast, a single 5 x 10(9) CFU dose of vaccine resulted in high rates (75% and 87%) of seroconversion with two different batches of vaccine. A batch prepared with a centrifugation step gave significantly higher geometric mean titres (16-fold increase over baseline) than did a batch in which there was a filtration step between fermentation and lyophilisation (10-fold increase over baseline). At a 5 x 10(9) CFU dose, CVD 103-HgR is well tolerated and highly immunogenic in Indonesian children and should therefore be further investigated for use as a one-dose live oral cholera vaccine in developing countries.", "A randomized, double-blind, placebo controlled trial was conducted in 50 healthy Swiss adults to assess the safety and immunogenicity of the live oral attenuated cholera vaccine candidate strain Vibrio cholerae CVD 103-HgR (classical, Inaba). A single dose of 5 x 10(8) viable CVD 103-HgR organisms, administered in a buffered liquid formulation, was well tolerated as compared with individuals who received an equivalent amount of heat-killed Escherichia coli K-12 placebo. Eighty-eight percent of subjects receiving CVD 103-HgR mounted a significant (greater than fourfold) rise in Inaba vibriocidal titre while 68% did so for the heterologous Ogawa serotype. The magnitude of the vibriocidal antibody response (as measured by peak geometric mean titre and by fold-rise in titre over baseline) was greater for the homologous Inaba serotype. Nineteen out of 25 volunteers (76%) responded with a significant (p less than 0.05) rise in serum antitoxin levels. No vaccinee who received the E. coli K-12 placebo mounted a significant rise in either vibriocidal or antitoxin antibody levels. These results corrobrate the safety and immunogenicity of CVD 103-HgR in healthy adult volunteers.", "Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXPhi prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 10(9) CFU of freshly harvested 638 buffered with 1.3% NaHCO(3), while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 10(9) CFU of DeltaCTXPhi attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 x 10(5) CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO(3). Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (10(9) CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent V. cholerae 3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation.", "A newly formulated, oral, inactivated whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was evaluated in US military personnel. In the first study, 74 subjects were given two doses 14 days apart. In the second study, 186 subjects were randomized into four groups; two groups received vaccine with either full (4 g) or half (2 g) strength bicarbonate buffer, and two groups received either full or half strength buffer without vaccine. Mild gastrointestinal symptoms were associated with full buffer (P = .02) but not with the vaccine. In the first study, 36% of all subjects and 55% with low prevaccination titers (< 1:40) had a > or = 2-fold rise in vibriocidal antibody level; > 80% of subjects developed a 4-fold rise in anti-cholera toxin (CT) titers. Post-vaccination IgA and IgG anti-CT titers were approximately 1.5-fold higher among persons receiving full strength buffer (P = .05). The WC/rBS vaccine is safe and immunogenic in North Americans, although some mild gastrointestinal symptoms occur with the high concentration of buffer necessary to protect the B subunit from gastric acid denaturation. Prior immunity to cholera conferred by parenteral vaccine decreased vibriocidal antibody response.", "A single dose (5 x 10(8) organisms) of attenuated A- B+ Vibrio cholerae classical Inaba recombinant vaccine strain CVD 103-HgR or placebo was administered to 24 healthy young Thai adults in a randomized, placebo-controlled, double-blind trial of safety and immunogenicity. None of the volunteers experienced untoward reactions. The vaccine strain was recovered from 2 of 12 vaccines. The vibriocidal antibody response (the best immunological correlate of protection) was good: 11 of 12 vaccinees (92%) manifested significant serotype-homologous Inaba antibody rises with a peak reciprocal geometric mean titer (RGMT) postvaccination of 3,417; 9 of 12 exhibited significant serotype-heterologous Ogawa antibody rises (prevaccination RGMT, 180; peak RGMT, 2,874). Nine of 12 vaccinees had significant rises in serum antitoxin. None of the controls exhibited rises in vibriocidal or antitoxic antibody. This preliminary study further confirms the safety and immunogenicity of CVD 103-HgR live oral cholera vaccine and paves the way for larger community studies of this candidate cholera vaccine.", "In order to evaluate the safety and immunogenicity of domestic produced lyophilized recombinant, B-subunit, inactivated whole cell vaccine of vibrio cholerae (rBS-WC), 369 subjects were randomly divided into three groups and observed with masking method, one with high dose of vaccine (5 mg rBS and 10\" WC), another with low dose (1 mg rBS and 10\" WC), and the control one with placebo. Three doses of vaccine were given orally at an interval of seven days and 14 days, respectively. Results showed that only one subject had mild adverse reaction in the vaccine group (1/247) and none in the control group. Serum and fecal antibody conversion rates and average levels of antibodies in the two vaccine groups were significantly higher than those in control one. There was no significant difference in serum and fecal antibody conversion rate and average antibody levels between the two vaccine groups. But, antibody response was different among subjects of various sex, age, and vaccine doses. It indicates that rBS-WC vaccine of vibrio cholerae had good immunogenicity and safety.", "The protective efficacy of an oral inactivated whole cell Vibrio cholerae plus recombinant B subunit cholera vaccine was determined against El Tor cholera among Peruvian children and adults (2-65 years old) in a randomized, double-blind manner. Study subjects received 2 doses of vaccine or placebo 2 weeks apart, followed by a booster dose 10 months later. Surveillance for cholera was performed actively, with 2 visits per week to each household, and passively, at a local hospital. Stool samples were collected during diarrhea episodes and were cultured for V. cholerae. A total of 17,799 persons received 2 doses of vaccine or placebo, and 14,997 of these persons received the booster dose. After 2 doses (first surveillance period), V. cholerae biotype O1 was isolated from 17 vaccinees and 16 placebo recipients, demonstrating vaccine efficacy (VE) of -4%. After 3 doses (second surveillance period), V. cholerae O1 was isolated from 13 vaccinees and 32 placebo recipients, demonstrating VE of 61% (95% confidence interval ¿CI, 28%-79%). In the second surveillance period, the VE for illness requiring hospitalization was 82% (95% CI, 27%-96%). VE was also higher for persons >15 years old (VE, 72%; 95% CI, 28%-89%).", "The cholera epidemic in South America has reinforced the need for safe and effective oral vaccines. In a randomised, double-blind, placebo-controlled efficacy trial among 1563 Peruvian military recruits we have investigated the protective efficacy of an oral inactivated whole-cell/recombinant-B-subunit (WC/rBS) cholera vaccine. Participants were given two oral doses of cholera vaccine or Escherichia coli K12 placebo, with an interval of 7-14 days. 1426 (91%) subjects received the two prescribed doses and were followed up for a mean of 18 weeks (median 21 weeks). After vaccination, Vibrio cholerae O1 El Tor Ogawa was isolated from 17 subjects with diarrhoea. 16 of the cholera cases occurred 2 weeks or longer after the second dose of vaccine (14 placebo recipients, 2 vaccinees). We also detected 14 symptomless infections (11 [7 placebo recipients, 4 vaccinees]) 2 weeks or longer after the second dose. The vaccine had significant protective efficacy against cholera (86% [95% CI 37-97], p < 0.01) but not against symptomless infection (42% [-96 to 85]). All cholera cases were in people of blood group O, who made up 76% of the study population (p < 0.01). Two doses of WC/rBS vaccine, given 1 to 2 weeks apart, provide rapid, short-term protection against symptomatic cholera in adult South Americans, who are predominantly of blood group O. Long-term efficacy studies in Peruvian adults and children are under way.", "CVD 103-HgR is an attenuated, AB+, live, recombinant vaccine strain, developed by deletion of the toxA gen in a virulent Vibrio cholerae 01, Inada classical strain (569B). In phase II studies conducted to date, CVD 103-HgR has been well tolerated and immunogenic in volunteers from both industrialized countries and cholera-endemic areas. In this study of safety, immunogenicity and excretion, 81 Chilean adults were randomly allocated to receive, in a double blind fashion, a single oral dose of 5 x 10(9) FU of CVD 103-HgR or placebo, (5 x 10(9) heat-killed E. Coli K12 organisms), in 100 ml of buffered water. Side effects were assessed by daily visits to the participants. Immunogenicity, (vibriocidal seroconversion), was investigated in blood drawn before and on days 8 and 28 after immunization, while stool cultures to assess excretion of the vaccine strain were performed on specimens obtained on days 1 and 7. None of the participants, (40 vaccinees and 41 placebo recipients), experienced untoward effects during 30 minutes of close surveillance after ingestion of the preparation; upon follow up, neither adverse events were more frequently reported by the vaccinees. 34/40 vaccinees, and 2/41 participants receiving placebo had a significant raise, (> = fourfold), in their vibriocidal titers; (85 vs 2%, p < 0.001). The peak postimmunization geometric mean titer, (222), was ten fold higher than the baseline vibriocidal titer. The vaccine strain was recovered in stool cultures from 8 participants, one of them excreted the strain in both specimens. We conclude that CVD-103-HgR is safe and immunogenic in Chilean adults.", "Serum responses to oral cholera vaccines were assessed in three paediatric vaccine trials, two in León, Nicaragua and one in Stockholm, Sweden. A calibrated anti-cholera toxin B subunit (CTB) IgA ELISA was used together with an assay for vibriocidal antibodies. Swedish children had lower pre-vaccination levels of antibody, but serum responses were more pronounced in Swedish children than in Nicaraguan children. Post-vaccination levels of anti-toxin antibody were generally above those found after natural infections with enterotoxigenic Escherichia coli, that cross-reacts serologically with Vibrio cholerae. Adverse events seen after vaccination were generally mild and of little clinical significance.", "Persons of blood group O are at increased risk of developing cholera gravis. In a randomized, placebo-controlled, double-blind safety-immunogenicity trial of live oral cholera vaccine CVD 103-HgR in 5- to 9-year-old Chilean children, vibriocidal antibody seroconversion (74% overall) did not differ by blood group. However, the reciprocal geometric mean titer (GMT) in blood group O vaccines (GMT = 486) was higher than that in non-O vaccines (GMT = 179) (P < 0.02).", "Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age.\n The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine \"cocktail\" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated.\n Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose.\n Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.", "Every year since its introduction in 1991, there have been epidemics of cholera in Lima, Peru. Vaccination is one approach to the control of cholera. A pilot study was conducted to assess the safety and immunogenicity of a whole cell plus recombinant B subunit (WC/rBS) cholrea vaccine in Lima, Peru. Five hundred and forty-one volunteers aged 2-65 years received two doses two weeks apart of WC/rBS vaccine or Escherichia coli K12 placebo administered in bicarbonate buffered water. Symptoms were monitored on all subjects and blood was collected from 102 persons before the first dose and two weeks after the second dose. Mild post-vaccination gastrointestinal symptoms were reported with equal frequency for both the vaccine and placebo recipients. Among 51 vaccines, 49% had a twofold or greater increase in serum vibriocidal titers (GMT = 78; range < 1:10 to 1:5120); and 92% and 82% developed a twofold or greater serum anti-cholera toxin IgG and IgA response, respectively. Persons with elevated prevaccination vibriocidal titers had a decreased response to the WC/rBS. Age and blood group did not affect the immune response. The WC/rBS vaccine was safe and immunogenic in a group of native Peruvians.", "Attenuated Vibrio cholerae oral vaccine CVD 103-HgR was well tolerated by 324 Thai soldiers and civilians. Most received a single 5 x 10(8) cfu dose, while 40 each received one or two 5 x 10(9) cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P less than .001). Increasing the vaccine dose to 5 x 10(9) cfu raised the geometric mean titer (P less than .001). A second 5 x 10(9) cfu dose one week later did not notably increase seroconversions. Likelihood of seroconversion was inversely correlated with baseline vibriocidal titer (P less than .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers less than or equal to 1:40, including 100% of civilians after one 5 x 10(8) cfu dose, 79% of soldiers after one 5 x 10(9) cfu dose, and 45% of soldiers after one 5 x 10(8) cfu dose. In persons with elevated baseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects, other measurements must be used. Study regimens in endemic areas should use a single 5 x 10(9) cfu dose.", "Groups of 122 Peruvian adults of low socioeconomic level (SEL) and 125 of high SEL received a randomly allocated 5 x 10(9)- or 5 x 10(8)-CFU dose of CVD 103-HgR live oral cholera vaccine or a placebo. The vaccine was well tolerated. Vibriocidal seroconversions occurred in 78% of high-SEL and 72% of low-SEL subjects who ingested the high dose and in 78 and 49%, respectively, of those who received the low dose.", "Immune responses after one and two doses of the reformulated killed oral cholera vaccine were measured in a double-blind, randomized, placebo-controlled trial of 77 adults aged 18-40 years and 77 children aged 1-17 years residing in Kolkata, India. 65% of adults and 87% of children and 46% of adults and 82% of children exhibited a > or =4-fold rise in serum Vibrio cholerae O1 vibriocidal antibody titers from baseline following dose 1 and 2, respectively. Responses to V. cholerae O139 were less pronounced but followed a similar pattern. We demonstrate that in a cholera-endemic area, the vaccine elicited vibriocidal responses after a single-dose of the vaccine.", "Despite considerable experience with single-dose, live, oral cholera vaccine CVD 103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in sub-Saharan Africa or on individuals infected with human immunodeficiency virus (HIV). We therefore conducted a randomized, placebo-controlled, double-blind, cross-over clinical trial in 38 HIV-seropositive (without clinical acquired immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and vomiting) were observed with similar frequency among vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV-seropositives with CD4+ counts below 500 per microliter. Following immunization, the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV-seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV-seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although serological responses were significantly attenuated among HIV-seropositives (particularly in those with CD4+ counts < 500 per microliter) relative to HIV-seronegatives. These results encourage further evaluations of this single-dose, oral cholera vaccine in high-risk populations such as refugees in sub-Saharan Africa.", "A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.", "Vietnam currently produces an orally administered, bivalent (O1 and O139) killed whole-cell vaccine and is the only country in the world with endemic cholera to use an oral cholera vaccine in public health practice. In order to allow international use, the vaccine had to be reformulated to meet World Health Organization (WHO) requirements. We performed a randomized, placebo controlled, safety and immunogenicity studies of this reformulated vaccine among Vietnamese adults. One hundred and forty-four subjects received the two-dose regimen and 143 had two blood samples obtained for analysis. We found that this reformulated oral killed whole-cell cholera vaccine was safe, well tolerated and highly immunogenic.", "We conducted a randomized trial among persons in rural Bangladesh to evaluate the side effects and immunogenicity of orally administered B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) cholera vaccines and a killed Escherichia coli strain K12 placebo proposed for field testing. Three doses of BS-WC, WC, E. coli, or a control agent were given with antacid to 1,257 women (aged greater than 15 years) and children (aged to to 15 years). The four groups exhibited no statistically significant differences in occurrence of symptoms after each dose, and rises in titers of vibriocidal (VC) antibodies to Inaba and Ogawa were twofold higher for vaccinees than for controls (P less than .001). Half of the persons with fourfold or greater VC responses to WC responded after the first dose; many additional patients, particularly young children, responded after subsequent doses. In contrast, 89% of persons who responded to BS-WC with twofold or greater rises in titer of IgG antibodies to cholera toxin did so after the first dose. After the third dose, vaccinees exhibited a fivefold higher rise in titer than did controls (P less than .001); a dose-to-dose booster effect was most evident in young children.", "A live oral Vibrio cholerae O1 El Tor vaccine, Peru-15 was tested in a double-blind, randomized placebo controlled study for safety and immunogenicity in Phase I and Phase II studies in 240 Bangladeshi children aged 9 months-5 years of age. Two different doses (2x10(7) and 2x10(8)cfu) were tested. Vaccination did not elicit adverse events and the strain was genetically stable. Vibriocidal antibody responses developed in 42/50 (84%) toddlers (2-5 years) and 35/50 (70%) of younger children (9-23 months) and overall 77/100 (77%) who received the high dose. LPS-IgA-antibody responses were seen in 60% of toddlers and 34% of infants; 40% responded with IgA antibodies to cholera toxin. The responses to the reduced dose was lower. These studies demonstrate that Peru-15 at a dose of 2x10(8)cfu is safe and immunogenic in children in Bangladesh.", "A live oral Vibrio cholerae O1 El Tor vaccine candidate, Peru-15, was studied for safety, immunogenicity, and excretion in phase 1 (inpatient) and phase 2 (outpatient) studies of Bangladeshi adults.METHODs. The study was conducted among adults, by use of a double-blind, randomized, placebo-controlled design. A single dose of Peru-15 (approximately 2 x 108 cfu) or placebo (buffer only) was given in standard bicarbonate and ascorbic acid buffer.RESULTS. Study treatment did not elicit any major adverse events in the volunteers, during either the inpatient or the outpatient phases, and there were no reports of diarrhea. V. cholerae was isolated from the stool of only 1 volunteer and was found to be genetically identical to the vaccine strain. Vibriocidal antibody responses were seen in 30 (75%) of 40 vaccine recipients and in 3 (10%) of 30 placebo recipients. Peripheral blood immunoglobulin (Ig) A and IgM antibody-secreting cell responses to lipopolysaccharide were seen in the majority of vaccine recipients (response rate, 78%--88%). Seroconversion for lipopolysaccharide-specific IgA antibodies was seen in 88% of vaccine recipients. The response in vaccine recipients was significantly higher than that in placebo recipients, in all of the immunological assays (P=.036 to <.001). A lower immunological response against cholera toxin B subunit was detected.CONCLUSIONS. The safety and immunogenicity of this Peru-15 vaccine candidate indicates the usefulness of future studies in Bangladesh, where cholera is endemic.", "Oral cholera vaccines consisting of killed whole cells have been available for many years, but they have not been used extensively in populations with endemic disease. An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk areas in Vietnam. To expand the use of this vaccine, it was modified to comply with WHO standards. We assessed the efficacy and safety of this modified vaccine in a population with endemic cholera.\n In this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged 1 year or older, were cluster-randomised by dwelling to receive two doses of either modified killed-whole-cell cholera vaccine (n=52 212; 1966 clusters) or heat-killed Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation was done by computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for the patient to seek treatment in a health-care facility. We undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo. We assessed first episodes of cholera that occurred between 14 days and 730 days after receipt of the second dose. This study is registered with ClinicalTrials.gov, number NCT00289224.\n 31 932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo (1757 clusters) received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related serious adverse events.\n This modified killed-whole-cell oral vaccine, compliant with WHO standards, is safe, provides protection against clinically significant cholera in an endemic setting, and can be used in children aged 1.0-4.9 years, who are at highest risk of developing cholera in endemic settings.\n Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, Governments of South Korea, Sweden, and Kuwait.", "Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe, highly immunogenic, single-dose live oral vaccine in adults in industrialized countries. Safety, excretion, immunogenicity, vaccine transmissibility, and environmental introduction of CVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta. In 81 households, 1 child was randomly allocated a single dose of vaccine (5 x 10(9) cfu) and another, placebo. Additionally, 139 unpaired children were randomly allocated vaccine or placebo. During 9 days of follow-up, diarrhea or vomiting did not occur more often among vaccines than controls. Vaccine was minimally excreted and was isolated from no controls and from 1 (0.6%) of 177 unvaccinated family contacts. A 4-fold or higher rise in serum vibriocidal antibody was observed in 75% of vaccines (10-fold rise in geometric mean titer over baseline). Of 135 paired placebo recipients or household contacts, 5 had vibriocidal seroconversions. Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine. These observations pave the way for a large-scale field trial of efficacy.", "Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model. A total of 59 volunteers were randomly allocated to groups to receive either 2 x 10(8) CFU of reconstituted, lyophilized Peru-15 vaccine diluted in CeraVacx buffer or placebo (CeraVacx buffer alone). Approximately 3 months after vaccination, 36 of these volunteers were challenged with approximately 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Among vaccinees, 98% showed at least a fourfold increase in vibriocidal antibody titers. After challenge, 5 (42%) of the 12 placebo recipients and none (0%) of the 24 vaccinees had moderate or severe diarrhea (> or = 3,000 g of diarrheal stool) (P = 0.002; protective efficacy, 100%; lower one-sided 95% confidence limit, 75%). A total of 7 (58%) of the 12 placebo recipients and 1 (4%) of the 24 vaccinees had any diarrhea (P < 0.001; protective efficacy, 93%; lower one-sided 95% confidence limit, 62%). The total number of diarrheal stools, weight of diarrheal stools, incidence of fever, and peak stool V. cholerae excretion among vaccinees were all significantly lower than in placebo recipients. Peru-15 is a well-tolerated and immunogenic oral cholera vaccine that affords protective efficacy against life-threatening cholera diarrhea in a human volunteer challenge model. This vaccine may therefore be a safe and effective tool to prevent cholera in travelers and is a strong candidate for further evaluation to prevent cholera in an area where cholera is endemic.", "We assessed the protective efficacy (PE) of three doses of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines in a randomized, double-blind trial among 62,285 children and women residing in rural Bangladesh. After one complete year of surveillance, 110 cases of cholera were detected in the placebo group, 52 in the WC group (PE, 53%; P less than .0001), and 41 in the BS-WC group (PE, 62%; P less than .0001). Protection was greater for BS-WC recipients than for WC recipients only during the initial eight months of observation. Both vaccines conferred equivalent protection against cholera associated with life-threatening dehydration and against less severe cholera. High-grade, sustained protection was observed in persons vaccinated when older than five years; in younger persons protection was transient. We conclude that BS-WC and WC vaccines confer significant protection against cholera, particularly in persons vaccinated when older than five years.", "An effective vaccine against cholera has been used for public health purposes in Vietnam since the 1990s. This vaccine was reformulated to meet WHO requirements. We assessed the safety and immunogenicity of the reformulated bivalent (Vibrio cholerae 01 and 0139) killed whole cell oral vaccine in a cholera endemic area in Kolkata, India.\n Double-blind, randomized, placebo controlled trial.\n The trial was conducted in the clinical trial ward of the Infectious Diseases Hospital in Kolkata, India.\n The participants were 101 healthy adults (males and non-pregnant females) aged 18-40 years and 100 healthy children (males and non-pregnant females) aged 1-17 years.\n Participants were randomized to receive either the bivalent killed whole cell oral cholera vaccine or placebo (killed oral Escherichia coli K12).\n For safety: proportion of subjects with adverse events during the duration of study participation. For immunogenicity: Proportion of subjects who had a > or = 4-fold rise in serum vibriocidal antibody titers 14 days after the second dose of vaccine or placebo.\n Adverse reactions were observed with similar frequency among vaccine and placebo recipients in both age groups. Among adults 4% of vaccine and 8% of placebo recipients and among children 4% of vaccine and 2% of placebo recipients had at least one adverse event within 28 days of the first dose of the vaccine. Following immunization, 53% of adult and 80% of children vaccinees showed a > or = 4 fold rise in serum V. cholerae O1 vibriocidal antibody titers. A less pronounced response to V. cholerae O139 vibriocidal antibody titers post-immunization was noted among vaccinees.\n We found the vaccine to be safe and immunogenic in a cholera-endemic area in India.\n ClinicalTrials.gov NCT00119197.", "CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1. A randomized, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-HgR (2 x 10(8) to 8 x 10(8) CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Ninety-one percent of the vaccinees had a >/=4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (>/=3-liter diarrheal stool) (P < 0.01; protective efficacy, 91%). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stool V. cholerae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among vaccinees was 4.9 x 10(2) CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.", "To assess the safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit cholera vaccine, 2 lots manufactured in June 1991 and February 1992 were tested in January 1995. Two oral doses of vaccine or placebo given 2 weeks apart were given with buffer to 216 Peruvian adults and children. Symptoms were elicited for 3 days after each dose. Serum and plasma specimens obtained from each volunteer before vaccination and 10-14 days after the second dose were tested for vibriocidal and anti-cholera toxin antibodies. The vaccine was well-tolerated. Nearly half of the 100 vaccinees had pre-vaccination vibriocidal titers > or = 1:40. Elevated titers were observed in 22% of 37 children 2-5 years of age compared with 66% of 63 vaccinees 6-65 years (P < 0.001). A > or =2-fold serum vibriocidal response was observed in 55% of 100 vaccinees and 6% of 32 placebo recipients. An elevated pre-vaccination titer (< or =1:40) did not change the proportion of vaccinees who responded with a > or =2-fold increase in vibriocidal titer (51% versus 59%, difference not significant), but did change the proportion responding with a > or =4-fold increase (41% versus 22%; P < 0.05). The vibriocidal seroconversion rate was lowest in children 2-5 years old despite low pre-vaccination titers. Two-fold or greater serum antitoxic responses in IgA and IgG were observed in >90% of the vaccinees; > or =4-fold responses were seen in 65-70% of the vaccinees with a 6-8-fold increase over baseline. Plasma specimens were as good as sera for determining anti-toxic antibodies by ELISA, but were less satisfactory for determining vibriocidal antibody titers.", "A randomized, double-blind, placebo-controlled efficacy trial of one dose of CVD 103-HgR live oral cholera vaccine was performed in Indonesia from 1993 to 1997. 67,508 persons aged 2-41 years ingested vaccine or placebo and were followed for four years, detecting cholera cases using hospital-based surveillance. A nested reactogenicity study (538 vaccinees, 535 controls) revealed no vaccine-attributable side effects. A nested immunogenicity study (N=657) showed vibriocidal seroresponses in 64-70% of vaccinees vs 1-2% of controls. Cholera incidence was lower than expected. 103 cases of Vibrio cholerae O1 El Tor diarrhea were detected, 93 evaluable for vaccine efficacy (43 vaccine, 50 placebo; efficacy=14%). A suggestion of protection was observed among persons with blood group O [P=0.12]. Only seven cases occurred within six months of vaccination, precluding assessment of short-term efficacy. In Jakarta, single-dose CVD 103-HgR did not confer long-term protection. Short-term protection from a single-dose and long-term protection from two doses have yet to be studied.", "A new live oral cholera vaccine, Peru-15, was studied for safety, immunogenicity, and excretion in 2 groups of healthy volunteers. Twelve inpatient volunteers received freshly harvested vaccine in doses of either 10(7) or 10(9) cfu. Subsequently 50 outpatient volunteers received freeze-dried vaccine in doses of 10(8) or 10(9) cfu or placebo in a three-cell, double-masked, placebo-controlled trial. The strain was well tolerated at all dose levels, and it stimulated high levels of vibriocidal antibodies in most inpatient volunteers and in all outpatient volunteers. Although antitoxin responses were less frequent and of lower magnitude than the vibriocidal responses, antitoxin responses were seen in >60% of the outpatient volunteers. About 60% of the volunteers excreted the vaccine in their feces; however, fecal excretion did not correlate with serologic responses. It is concluded that Peru-15 is a safe and immunogenic oral vaccine for cholera.", "Several studies have shown that orally administered killed cholera vaccines are safe and protective in populations at risk of cholera in developing countries. However, these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children. We have tested an inexpensive, killed whole-cell cholera vaccine developed and produced in Vietnam.\n The efficacy of the vaccine was assessed in a large-scale, open field trial in people at least 1 year old residing in 22,653 households in the central coastal city of Hue. Alternate households were assigned vaccine (67,395 people; two doses per person) or no vaccine (67,058 people). Surveillance for cholera was conducted in all Ministry of Health facilities serving this population. Analysis was by intention to treat.\n During an outbreak of El Tor cholera 8-10 months after vaccination, 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group, and 92 cases among age-eligible people allocated to the no-vaccine group (protective impact 60% [95% CI 40-73]). Among the 51,975 people who received the complete two-dose vaccine regimen, the protective efficacy was 66% (46-79): in this subset, the protective efficacy was similar for children aged 1-5 years (68%) and for older people (66%).\n These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children, who are at highest risk of cholera in endemic settings. An inexpensive, locally produced, and effective oral cholera vaccine may be within reach of the limited health-care budgets of poor countries with endemic cholera, if our findings can be replicated in a randomised double-blind trial.", "We conducted a double-blind, placebo-controlled, randomized crossover study to evaluate the safety and immunogenicity of a single 5 x 10(8)-CFU dose of live oral recombinant cholera vaccine CVD 103-HgR in 94 North American adults. The vaccine was well tolerated without associated adverse reactions. Despite minimal fecal excretion of vaccine, 97% of subjects exhibited serum vibriocidal antibody and 72% had antitoxin responses.", "A 'double-blind', randomized, placebo controlled study of an oral inactivated whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was conducted during February-March 1992 in Peru in 346 military recruits, 307 (89%) of whom received 2 oral doses of vaccine or Escherichia coli K12 placebo, 2 weeks apart. Paired serum samples were obtained from 155 (50%) of the recipients of 2 doses. An epidemic of cholera took place between doses. No difference in cholera attack rates was detected between vaccine and placebo recipients after one dose (8% versus 14%). Seroconversion (4-fold or higher increase in vibriocidal antibody titres) was detected in 90% and 80% of vaccine and placebo recipients, respectively, with low pre-existing vibriocidal titres (< 0.01). The anti-cholera toxin seroconversion rate among those with low pre-existing titres was higher in vaccinated subjects (97%) than in placebo recipients (68%) (P < 0.01). Administration of 2 doses of WC/rBS vaccine concomitantly with natural V. cholerae O1 infection enhanced the serum anti-cholera toxin response. The immune response to the whole cell component of the vaccine was reduced by high pre-existing vibriocidal antibody titres.", "In January and February 1992, an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells (rBS/WC) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla, Colombia. This was a randomized, double-blind placebo-controlled study. Participants received two doses of either the vaccine or a placebo (killed Escherichia coli K12) over a two-week interval. Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second. Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins. Geometric mean titers (GMT) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine. In the paired samples taken from vaccinated subjects, two-fold or greater increases were observed in 44% and four-fold or greater increases were observed in 34%, as compared to similar increases in 9.2% and 2.2% of the sera taken from those receiving the placebo (P < 0.05). The GMTs of IgG and IgA antitoxins, as determined by ELISA, increased by factors of 4 and 3.2, respectively, in those receiving the vaccine, as compared to factors of 1.1 and 1.1 in those given the placebo (P < 0.001 for IgG, P < 0.01 for IgA). Approximately 80% of the paired samples from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5, as compared to only about 20% of those in the placebo group (P < 0.000001). Belonging to the O blood group did not significantly affect the immune response. Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects. The two doses of oral vaccine were found to be safe and without attributable side-effects. The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine.", "Vibrio cholerae 638 (El Tor, Ogawa), a new CTXPhi-negative hemagglutinin/protease-defective strain that is a cholera vaccine candidate, was examined for safety and immunogenicity in healthy adult volunteers. In a double-blind placebo-controlled study, no significant adverse reactions were observed in volunteers ingesting strain 638. Four volunteers of 42 who ingested strain 638 and 1 of 14 who received placebo experienced loose stools. The strain strongly colonized the human small bowel, as evidenced by its isolation from the stools of 37 of 42 volunteers. V. cholerae 638, at doses ranging from 4 x 10(7) to 2 x 10(9) vibrios, elicited significant serum vibriocidal antibody and anti-Ogawa immunoglobulin A antibody secreting cell responses.", "To evaluate a killed oral cholera vaccine produced in Viet Nam, and to compare the Vietnamese vaccine with one that is licensed internationally.\n Two-dose regimens of a locally produced, bivalent, anti-O1, anti-O139 killed oral whole-cell cholera vaccine (biv-WC) and of a commercially available, monovalent (anti-O1) oral recombinant B subunit-killed whole-cell cholera vaccine (rBS-WC) were compared in two trials in Viet Nam. In the first trial, 144 adults were randomized to biv-WC with or without buffer, rBS-WC with buffer, or placebo without buffer. In the second, 103 children aged 1-12 years were randomized to biv-WC without buffer, rBS-WC with buffer, or placebo without buffer.\n No regimen was associated with significant side-effects. In adults, ca 60% of recipients of either vaccine exhibited at least fourfold serum anti-O1 vibriocidal antibody responses and ca 40% of recipients of biv-WC demonstrated anti-O139 vibriocidal responses. Both anti-O1 (ca 90% in each vaccine groupand anti-O139 (68% in the biv-WC group) vibriocidal responses occurred more frequently in children. The responses to biv-WC were unaffected by the receipt of buffer.\n It was concluded that biv-WC was safe and immunogenic, that it could be administered without buffer, and that it could elicit robust immune responses even in children, for whom the risk of endemic cholera is highest." ]

[ "15244227", "10228287", "15861196", "15580195" ]

[ "Randomized controlled trial of skin-to-skin contact from birth versus conventional incubator for physiological stabilization in 1200- to 2199-gram newborns.", "Effect of polyethylene occlusive skin wrapping on heat loss in very low birth weight infants at delivery: a randomized trial.", "Heat loss prevention for preterm infants in the delivery room.", "Heat Loss Prevention (HeLP) in the delivery room: A randomized controlled trial of polyethylene occlusive skin wrapping in very preterm infants." ]

[ "Conventional care of prematurely born infants involves extended maternal-infant separation and incubator care. Recent research has shown that separation causes adverse effects. Maternal-infant skin-to-skin contact (SSC) provides an alternative habitat to the incubator, with proven benefits for stable prematures; this has not been established for unstable or newborn low-birthweight infants. SSC from birth was therefore compared to incubator care for infants between 1200 and 2199 g at birth.\n This was a prospective, unblinded, randomized controlled clinical trial; potential subjects were identified before delivery and randomized by computerized minimization technique at 5 min if eligible. Standardized care and observations were maintained for 6 h. Stability was measured in terms of a set of pre-determined physiological parameters, and a composite cardio-respiratory stabilization score (SCRIP).\n 34 infants were analysed in comparable groups: 3/18 SSC compared to 12/13 incubator babies exceeded the pre-determined parameters (p < 0.001). Stabilization scores were 77.11 for SSC versus 74.23 for incubator (maximum 78), mean difference 2.88 (95% CI: 0.3-5.46, p = 0.031). All 18 SSC subjects were stable in the sixth hour, compared to 6/13 incubator infants. Eight out of 13 incubator subjects experienced hypothermia.\n Newborn care provided by skin-to-skin contact on the mother's chest results in better physiological outcomes and stability than the same care provided in closed servo-controlled incubators. The cardio-respiratory instability seen in separated infants in the first 6 h is consistent with mammalian \"protest-despair\" biology, and with \"hyper-arousal and dissociation\" response patterns described in human infants: newborns should not be separated from their mothers.", "Significant evaporative heat loss in the very low birth weight infant can occur in the delivery room. We investigated the effect of polyethylene wrap applied immediately at birth (without drying) on rectal temperature measured at nursery admission.\n Sixty-two consecutive infants delivered at <32 weeks' gestation were stratified by gestational age and randomly allocated to resuscitation with polyethylene wrap. All infants were resuscitated under radiant warmers. Wraps were removed on nursery admission. Rectal temperature was taken by digital electronic thermometer.\n Fifty-nine of 62 recruited infants completed the study. Maternal temperature, delivery room temperature, transfer-incubator temperature, and time to admission were recorded. Use of occlusive wrapping resulted in a significantly higher admission rectal temperature in infants <28 weeks' gestation (difference in means = 1.9 C, P <.001). No significant difference was seen in admission rectal temperature in infants of 28 to 31 weeks' gestation (difference in means = 0.17 C, P =.47). All 5 deaths were in the nonwrap group (vs wrap, P =.04); their mean temperature was 35.1 C versus 36.5 C in survivors (P =.001).\n Occlusive wrapping of very low birth weight infants at delivery reduces postnatal temperature fall. This may result in a decreased mortality rate.", "Preterm infants are prone to hypothermia immediately following birth. Among other factors, excessive evaporative heat loss and the relatively cool ambient temperature of the delivery room may be important contributors. Most infants <29 weeks gestation had temperatures <36.4 degrees C on admission to our neonatal unit (NICU). Therefore we conducted a randomized, controlled trial to evaluate the effect of placing these infants in polyurethane bags in the delivery room to prevent heat loss and reduce the occurrence of hypothermia on admission to the NICU.\n After parental consent was obtained, infants expected to be <29 weeks gestation were randomized to intervention or control groups just prior to their birth. Infants randomized to the intervention group were placed in polyurethane bags up to their necks immediately after delivery before being dried. They were then resuscitated per NRP guidelines, covered with warm blankets, and transported to the NICU, where the bags were removed and rectal temperatures were recorded. Control infants were resuscitated, covered with warm blankets, and transported without being placed in polyurethane bags. Delivery room temperatures were recorded so this potentially confounding variable could be assessed.\n Intervention patients were less likely than control patients to have temperature < 36.4 degrees C on admission , 44 vs 70% (p<0.01) and the intervention group had a higher mean admission temperature, 36.5 degrees C vs 36.0 degrees C (p<0.003). This effect remained significant (p<0.0001) when delivery room temperature was controlled in analysis. Warmer delivery room temperatures (>/=26 degrees C) were associated with higher admission temperatures in both intervention and control infants, but only the subgroup of intervention patients born in warmer delivery rooms had a mean admission temperature >36.4 degrees C.\n Placing infants <29 weeks gestation in polyurethane bags in the delivery room reduced the occurrence of hypothermia and increased their NICU admission temperatures. Maintaining warmer delivery rooms helped but was insufficient in preventing hypothermia in most of these vulnerable patients without the adjunctive use of the polyurethane bags.", "To determine if polyethylene occlusive skin wrapping of very preterm infants prevents heat loss after delivery better than conventional drying and to evaluate if any benefit is sustained after wrap removal.\n This was a randomized controlled trial of infants <28 weeks' gestation. The experimental group was wrapped from the neck down. Only the head was dried. Control infants were dried completely. Rectal temperatures were compared on admission to the neonatal intensive care unit immediately after wrap removal and 1 hour later.\n Of 55 infants randomly assigned (28 wrap, 27 control), 2 died in the delivery room and 53 completed the study. Wrapped infants had a higher mean rectal admission temperature, 36.5 degrees C (SD, 0.8 degrees C), compared with 35.6 degrees C (SD, 1.3 degrees C) in control infants ( P = .002). One hour later, mean rectal temperatures were similar in both groups (36.6 degrees C, SD, 0.7 degrees C vs 36.4 degrees C, SD, 0.9 degrees C, P = .4). Size at birth was an important determinant of heat loss: Mean rectal admission temperature increased by 0.21 degrees C (95% CI, 0.04 to 0.4) with each 100-g increase in birth weight.\n Polyethylene occlusive skin wrapping prevents rather than delays heat loss at delivery in very preterm infants." ]

[ "779796" ]

[ "Controlled trial of cyclophosphamide in rheumatoid arthritis." ]

[ "Twenty-four patients with severe progressive rheumatoid arthritis were randomly assigned to cyclophosphamide or placebo in a double-blind crossover trial. Eleven patients who completed 9 months on cyclophosphamide (average dose: 1.8 mg/kg/day) demonstrated significant decrease in painful joints, swollen joints, and morning stiffness and increase in grip strength when compared to 11 patients on placebo. After crossover, significant improvement was observed in patients switched to cyclophosphamide, and deterioration within 2 months was observed in most patients changed from drug to placebo. Serum immunoglobulins and rheumatoid factor titers decreased with cyclophosphamide but antibody response to Vi antigen was unaffected. Primary delayed immune response to 2,4-dinitrochlorobenzene was markedly depressed. Adverse effects were troublesome--hemorrhagic cystitis affected 4 patients and amenorrhea occurred in 3. Despite striking beneficial effect, cyclophosphamide should be prescribed cautiously and only in severe resistant cases of rheumatoid arthritis." ]

[ "7901636", "19639462", "15777891", "14257025", "7002529", "17928802", "17435611", "12532571", "508702", "15231078", "20546462", "21147712", "11262469", "9508353", "4890375", "16319260", "11053509", "11904617", "14617464" ]

[ "Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia.", "Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study.", "Oral versus high dose parenteral iron supplementation in pregnancy.", "PARENTERAL IRON THERAPY IN PREGNANCY.", "Iron deficiency anaemia during pregnancy a comparative trial of treatment by iron-poly (sorbitol-gluconic acid) complex Ferastral given intramuscularly and iron dextran (Imferon) by total dose infusion.", "Should we lower the dose of iron when treating anaemia in pregnancy? A randomized dose-response trial.", "Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anemia in pregnant women.", "Comparative study--efficacy, safety and compliance of intravenous iron sucrose and intramuscular iron sorbitol in iron deficiency anemia of pregnancy.", "WHO sponsored collaborative studies on nutritional anaemia in India. The effect of parenteral iron administration in the control of anaemia of pregnancy.", "[The effectiveness of three regimens using ferrous sulfate to treat anemia in pregnant women].", "A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy.", "A combination of iron and retinol supplementation benefits iron status, IL-2 level and lymphocyte proliferation in anemic pregnant women.", "Efficacy and safety of intravenously administered iron sucrose with and without adjuvant recombinant human erythropoietin for the treatment of resistant iron-deficiency anemia during pregnancy.", "A comparison between intravenous iron polymaltose complex (Ferrum Hausmann) and oral ferrous fumarate in the treatment of iron deficiency anaemia in pregnancy.", "Controlled-release iron therapy in pregnancy.", "Intravenous versus oral iron for treatment of anemia in pregnancy: a randomized trial.", "Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial.", "Iron therapy in iron deficiency anemia in pregnancy: intravenous route versus oral route.", "A comparative study between intramuscular iron dextran and oral ferrous sulphate in the treatment of iron deficiency anaemia in pregnancy." ]

[ "Nutritional anaemia, thought to be caused by iron deficiency, affects 50-70% of pregnant women in the developing world. The influence of vitamin A and iron supplementation was studied in anaemic pregnant women in West Java, in a randomised, double-masked, placebo-controlled field trial. 251 women aged 17-35 years, parity 0-4, gestation 16-24 weeks, and haemoglobin between 80 and 109 g/L were randomly allocated to four groups: vitamin A (2.4 mg retinol) and placebo iron tablets; iron (60 mg elemental iron) and placebo vitamin A; vitamin A and iron; or both placebos, all daily for 8 weeks. Maximum haemoglobin was achieved with both vitamin A and iron supplementation (12.78 g/L, 95% Cl 10.86 to 14.70), with one-third of the response attributable to vitamin A (3.68 g/L, 2.03 to 5.33) and two-thirds to iron (7.71 g/L, 5.97 to 9.45). After supplementation, the proportion of women who became non-anaemic was 35% in the vitamin-A-supplemented group, 68% in the iron-supplemented group, 97% in the group supplemented with both, and 16% in the placebo group. Improvement in vitamin A status may contribute to the control of anaemic pregnant women.", "To compare the effects of bovine lactoferrin with ferrous sulfate on iron nutritional status and to evaluate their tolerability in 100 pregnant women with iron deficiency anemia.\n Prospective, randomized, controlled, double blind trial.\n Obstetrics clinic of a University Department of Obstetrics and Gynecology.\n One-hundred pregnant, healthy women to be treated either with one capsule of 100 mg bovine lactoferrin twice a day (Group A; n=49) and 520 mg ferrous sulfate once a day (Group B; n=48).\n After 30 days, we evaluated hemoglobin (Hb), serum ferritin, serum iron and total iron- binding capacity (TIBC) values. All women were asked to keep a diary of five potential gastrointestinal side effects (abdominal pain, nausea, vomiting, diarrhea and constipation). For each symptom, patients had to rate its severity according to a scale ranging from 0 (absent) to 3 (severe).\n Hb level before and after treatment. Secondary outcomes were serum ferritin, serum iron and TIBC levels and the difference in symptom scores between groups.\n In Groups A and B, Hb, serum ferritin and iron were significantly increased while TIBC was significantly reduced in comparison with basal values. No significant differences were observed between Groups A and B. The median scores of abdominal pain and constipation were significantly higher in patients treated with ferrous sulfate in comparison with those treated with bovine lactoferrin.\n The results show that bovine lactoferrin has the same efficacy as ferrous sulfate in restoring iron deposits with significantly fewer gastrointestinal side effects.", "To compare the effect of daily oral iron supplementation with two injections of high dose parenteral iron.\n A total of 220 pregnant women with a singleton pregnancy and hemoglobin between 8 to 11 g% at 16-24 weeks gestation were identified and randomly divided into two groups. Group A was started on daily oral iron therapy of 100 mg of elemental iron. Group B was given 250 mg of iron sorbitol intramuscularly and repeated at an interval of 4-6 weeks. Blood indices were evaluated at the beginning of study and at 36 weeks to see the effect after iron supplementation in the two groups. The data were analyzed using SPSS software, version 10.1.\n Definitive and comparable improvement in hemoglobin and all the blood indices (hematocrit, MCH, MCHC, MCV, Serum iron and TIBC) was observed. The absolute change in hemoglobin and hematocrit was 1.18+/-0.68 g% and 4.02+/-2.59% in oral group, 1.34+/-0.77 g% and 4.93+/-3.65% in parenteral group, respectively. Serum ferritin showed statistically significant absolute rise (10.43+/-7.92 microg/dl) after parenteral iron supplementation as compared to oral iron supplementation (9.76+/-4.78 microg/dl). Obstetric outcome was comparable in two groups.\n Two treatment regimens are biologically equivalent in terms of hematological response. Two high doses of intramuscular iron can be a good substitute to meet iron requirement in pregnancy.", "nan", "nan", "To compare the efficacy and side effects of low-dose vs high-dose iron supplements to correct anaemia in pregnancy.\n One hundred and eighty women with anaemia (haemoglobin <110 g l(-1)) in mid-pregnancy. The women were randomly allocated to 20; 40 or 80 mg of iron daily for 8 weeks from mid-pregnancy.\n One hundred and seventy-nine (99%) women completed the trial. At the end of treatment, there was a clear dose-response of increasing mean haemoglobin concentration with iron dose (111+/-13 g l(-1) at 20 mg per day, 114+/-11 g l(-1) at 40 mg per day and 119+/-12 g l(-1) at 80 mg per day, P=0.006). However, the incidence of anaemia did not differ statistically between groups. Compared with women in the 80 mg iron group, the odds ratio of anaemia was 1.9 (95% CI: 0.8, 4.3, P=0.130) and 1.1 (95% CI: 0.5, 2.6, P=0.827), respectively, for women in the 20 mg iron group and the 40 mg iron group. The incidence of gastrointestinal side effects was significantly lower for women in the 20 mg iron group compared with women in the 80 mg iron group; the odds ratio was 0.4 (95% CI: 0.2, 0.8, P=0.014) for nausea, 0.3 (95% CI: 0.2, 0.7, P=0.005) for stomach pain and 0.4 (95% CI: 0.2, 0.9, P=0.023) for vomiting.\n Low-dose iron supplements may be effective at treating anaemia in pregnancy with less gastrointestinal side effects compared with high-dose supplements.", "The efficacy of iron polymaltose complex (IPC) in the treatment of iron deficiency anemia (IDA) during pregnancy has not been well established, and the evidence is inconclusive.\n The aim of the study was to compare efficacy, safety, compliance, and cost-effectiveness of IPC with ferrous sulphate (FS) in pregnant patients.\n The randomized, double-blind, parallel-group study was conducted in the Department of Pharmacology in collaboration with the Department of Obstetrics and Gynaecology Postgraduate Institute of Medical Education and Research, Chandigarh, India.\n One hundred pregnant women aged 20-40 years at 14 to 27 weeks' gestation, with hemoglobin (Hb) < 9 g/dL, and serum ferritin < 12 mcg/L, were classified into 2 groups. One group received IPC (100 mg elemental iron), and the other group received FS (120 mg elemental iron) daily for 8 weeks. At Week 0 and Week 8, Hb, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron, and serum ferritin were measured. Compliance with study medication was determined by pill counting at each visit. Cost minimization analysis was done to compare the costs of the 2 treatments. Statistical Analysis: Data are expressed as mean -/+ SD. Paired and unpaired 't' test were used to analyze differences within groups and between groups. Chi-square (x2) test was used to analyze primary efficacy parameters and adverse drug reactions (ADR).\n Statistically significant increases in Hb, PCV, MCV, MCH, MCHC, serum iron, and serum ferritin levels were seen at the end of 8 weeks of treatment in both groups. The overall adverse effects were more common in the FS group compared with the IPC group [41 (78%) vs 15 (31%), P < .001]. The compliance rate was significantly (P < .05) higher for the IPC (91%) group than for the FS (87%) group. The average total cost (direct + indirect) of treatment of anemia was comparable between the 2 groups.\n The results of the present study suggest that IPC can be considered as a useful alternative formulation for the treatment of IDA during pregnancy for those patients who cannot tolerate other iron preparations (ferrous form); this is an important finding, as compliance is a significant concern during pregnancy.", "(1) To determine an alternative iron supplementation with better efficacy, compliance & safety in treatment of iron deficiency anemia during pregnancy, (2) to reduce blood transfusion during pregnancy, labor and puerperium.\n A prospective comparative study. A total number of 60 pregnant women with the gestational age of 12-34 weeks were included in the study who were suffering from iron deficiency anemia. They were divided in 3 groups (A, B and C). Group A (n = 15) received intravenous iron sucrose according to recommended dose containing 500 mg of iron sucrose for storage, in group B (n = 20) iron sucrose was administered according to deficit calculated as per formula but 200 mg of iron was given for storage instead of 500 mg, to reduce cost. While group C received intra muscular iron Sorbitol in the dose used as practice.\n Mean hemoglobin in group A and B was 8.0 +/- 1.1 g/dl and 8.9 +/- 0.7 respectively, in group C, it was 8.8 +/- 0.9 g/dl. In group A & B initial hemoglobin was assessed 3 weeks post therapy which showed an average rise of 2.8 g/dl (group A) and 1.9 g/dl (group B) and second assessment of Hemoglobin was done prior to delivery (ave: 6.6 weeks) showed a total rise of 3.8 g/dl (group A) and 2.4 g/dl (group B). Pre delivery mean Hemoglobin in group A and B was 11.8 g/dl and 11.3 g/dl respectively. In group C, the Hemoglobin was assessed only prior to delivery (average: 8.4 weeks from the start of therapy), and a rise of 1.4 g/dl was observed with pre delivery mean Hemoglobin of 10.2 g/dl. Target hemoglobin levels i.e. 11 g/dl was achieved by 80% in Group A, 70% in Group B and 28% in Group C by the time of delivery. Blood transfusion was not required in any group. In group A and B one patient had moderate abdominal pain, 2 had weakness and shivering and 3 had phlebitis at the site where intravenous canula was retained. None of patient discontinued the therapy due to any adverse effect. In group C majority complained of pain at injection site while 5 patients dropped out from the study due to intolerance.\n Intravenous iron therapy is safe, convenient and more effective then intramuscular iron therapy in treatment of iron deficiency anemia during pregnancy. The intravenous iron therapy can replace blood transfusion in antenatal period.", "1. The relative efficacy of oral and parenteral iron administration in the prophylaxis and treatment of Fe-deficiency anaemia of pregnancy has been studied. 2. Intravenous administration of Fe by total dose infusion of Fe dextran was not superior to oral Fe 120 mg/d, 6 d/week for 10-12 weeks. 3. Intramuscular Fe dextran, 100 mg twice per week for 10-12 weeks, produced a significantly greater rise in mean haemoglobin concentration than oral Fe therapy. 4. The superiority of intramuscular Fe as compared with intravenous Fe is probably related to the different handling of the Fe dextran by the reticulo-endothelial system. 5. In spite of the better response to intramuscular Fe dextran, it is not recommended for public health practice because of the risks associated with its use and the much higher cost of the preparation and its delivery.", "To evaluate the effectiveness of three regimens employing ferrous sulfate to treat pregnant women with anemia.\n The study was carried out at the Women's Health Center of the Pernambuco Institute of Maternal and Child Health in the city of Recife, Pernambuco, Brazil, from May 2000 to December 2001. A randomized clinical trial with blinded laboratory analysis was conducted. Iron (60 mg) was administered as 300-mg ferrous sulfate tablets. The women were allocated to three treatment groups, according to the frequency of ingesting the tablets: once a week (48 women), twice a week (53 women), and once a day (49 women). The groups were compared for the values for hemoglobin (Hb) concentration, mean corpuscular volume, and ferritin before and after the treatment.\n Before the intervention, the groups were homogeneous. They had the following mean (+/- standard deviation) concentrations of hemoglobin: 10.2 +/- 0.5 g/dL for the group receiving iron once a week, 10.2 +/- 0.6 g/dL for the group receiving iron twice a week, and 10.1 +/- 0.6 g/dL for the group receiving iron once a day. The means of corpuscular volume were, respectively: 88.5 +/- 5.0 fL, 87.6 +/- 5.9 fL, and 88.7 +/- 5.1 fL. The respective medians for ferritin were 30.2 ng/mL, 37.1 ng/mL, and 52.9 ng/mL. The cure rate (Hb > 11 g/dL) was 27% in the patients treated once a week, 34% in those treated twice a week, and 47% in the women treated daily. Treatment failure (hemoglobin < 10 g/dL) was seen in 41.6%, 13.2%, and 2.0% of the patients in the respective groups. Interruption of treatment due to diarrhea or epigastric pain occurred only among the patients treated daily.\n The regimen with iron administered daily is still the best option for treating anemia. However, treatment with ferrous sulfate administered twice a week is an alternative for patients who are unable to adhere to daily treatment.", "Iron deficiency anaemia is the most common deficiency disorder in the world, affecting more than one billion people, with pregnant women at particular risk.\n We conducted a single site, prospective, nonblinded randomized-controlled trial to compare the efficacy, safety, tolerability and compliance of standard oral daily iron versus intravenous iron.\n We prospectively screened 2654 pregnant women between March 2007 and January 2009 with a full blood count and iron studies, of which 461 (18%) had moderate IDA. Two hundred women matched for haemoglobin concentration and serum ferritin level were recruited.\n Patients were randomized to daily oral ferrous sulphate 250 mg (elemental iron 80 mg) with or without a single intravenous iron polymaltose infusion.\n Prior to delivery, the intravenous plus oral iron arm was superior to the oral iron only arm as measured by the increase in haemoglobin level (mean of 19.5 g/L vs. 12 g/L; P < 0.001); the increase in mean serum ferritin level (222 microg/L vs. 18 ug/L; P < 0.001); and the percentage of mothers with ferritin levels below 30 microg/L (4.5% vs. 79%; P < 0.001). A single dose of intravenous iron polymaltose was well tolerated without significant side effects.\n Our data indicate that intravenous iron polymaltose is safe and leads to improved efficacy and iron stores compared to oral iron alone in pregnancy-related IDA.", "Iron and vitamin A deficiencies impact anemia and the immune system.\n to investigate the effect of iron combined with retinol supplementation on iron status, IL-2 level and lymphocyte proliferation.\n a double-blind randomized trial conducted over 2 months. We randomly allocated 186 anemic pregnant women with 80 ≤ Hb 0 < 110 g/L into four groups. Group I (n=47) was supplemented daily with 60 mg iron as ferrous sulfate, IF (n=46) with 60 mg iron and 0.4 mg folic acid, IR (n=46) with 60 mg iron, 2.0 mg retinol and 0.4 mg folic acid and C (n=47) was the placebo group,.\n after the 2 months trial, there were considerable increases of iron status in Hb, plasma iron and ferritin in the I, IF and IR groups compared with Group C. Increases in plasma iron and ferritin in the IR group were also significantly greater than in Groups I and IF. Compared with group C, increases of IL-2 levels were 119, 184 and 206 ng/L; and lymphocyte proliferation increased by 0.095, 0.112 and 0.219 in Groups I, IF and IR, respectively. Increases of IL-2 were 65.3 ng/L and 87.5 ng/L in Groups IF and IR, greater than in Group I (both p values <0.01); and lymphocyte proliferation in Group IR were 0.124 and 0.107, also greater than in Groups I and IF, respectively.\n iron combined retinol supplementation was more beneficial to improving iron status and lymphocyte proliferation during pregnancy than iron alone.", "This study was undertaken to determine the efficacy and safety of intravenously administered iron sucrose with versus without adjuvant recombinant human erythropoietin in the treatment of gestational iron-deficiency anemia resistant to therapy with orally administered iron alone.\n Forty patients with gestational iron-deficiency anemia were randomly assigned to receive intravenously iron sucrose plus recombinant human erythropoietin or iron sucrose alone twice weekly. Target hemoglobin value was 11.0 g/dL. Efficacy measures were reticulocyte count, increase in hematocrit, and time to target hemoglobin level (treatment duration in weeks and need for continued therapy after 4 weeks).\n Both regimens were effective, but with adjuvant recombinant human erythropoietin the reticulocyte counts were higher from day 4 (P<.01), increases in hematocrit were greater from day 11 (P <.01), and the median duration of therapy was shorter (18 vs 25 days), with more patients reaching the target hemoglobin level by 4 weeks of treatment (n = 19 vs. n = 15). The groups did not differ with respect to maternal-fetal safety parameters.\n Adjuvant recombinant human erythropoietin safely enhanced the efficacy of iron sucrose in the treatment of gestational iron-deficiency anemia resistant to orally administered iron alone.", "Anaemia is the most common medical disorder in pregnancy with iron deficiency anaemia accounting for the majority of cases. Over 90% of the iron deficiency anaemia is due to red cell iron deficiency associated with depleted iron stores and deficient intake. The two main modalities of treating iron deficiency anaemia are oral or parenteral iron. Ferrous Hausmann (iron dextrin) is the latest iron preparation which can be used for intravenous parenteral administration as a total dose infusion. This study compares the efficacy of Ferrum Hausmann with oral ferrous fumarate therapy in the treatment of iron deficiency anaemia in pregnancy. Our study shows that treatment with intravenous Ferrum Hausmann (iron dextrin) resulted in a significantly better level and rate of increase of haemoglobin (p<0.001). Serum ferritin, which is the best indicator of iron stores, was significantly higher (p<0.001) in the intravenous group. Other indices of iron status such as serum iron, serum transferrin and zinc protoporphyrin also showed a significant improvement in the intravenous group compared to those given oral iron. The results suggest that intravenous iron as a total dose infusion is able to replenish iron stores more efficiently, completely and at a faster rate than oral iron therapy, thus providing the fuel for stimulation of full erythopoiesis compared to oral iron. There were also no reports of any adverse reactions with intravenous iron dextrin, whereas there were a considerable proportion of women on oral iron therapy who reported side effects. In conclusion, intravenous iron therapy with Ferrous Hausmann (iron dextrin) is a suitable, effective and safe alternative to oral iron therapy in the treatment of iron deficiency anaemia in pregnancy.", "nan", "The aim of this study was to compare the efficacy of intravenous iron to oral iron in the treatment of anemia in pregnancy.\n In this randomized open-label study, 90 women with hemoglobin levels between 8 and 10.5 g/dL and ferritin values less than 13 microg/L received either oral iron polymaltose complex (300 mg elemental iron per day) or intravenous iron sucrose. The iron sucrose dose was calculated from the following formula: weight before pregnancy (kg) x (110 g/L - actual hemoglobin [g/L]) x 0.24 + 500 mg. Treatment efficacy was assessed by measuring hemoglobin and ferritin on the 14th and 28th days and at delivery, and the hemoglobin on the first postpartum day. Adverse drug reactions, fetal weight, hospitalization time, and blood transfusions were also recorded.\n Hemoglobin values varied significantly with time between groups (interaction effect, P < .001). The change in hemoglobin from baseline was significantly higher in the intravenous group than the oral group at each measurement; the changes with respect to subsequent hemoglobin were significantly higher on the 14th (P = .004) and 28th (P = .031) days. Ferritin values were higher in patients receiving intravenous iron throughout pregnancy. No serious adverse drug reactions were observed. Fetal weight and hospitalization time were similar in the 2 groups. Blood transfusion was required for only one patient in the oral group.\n Intravenous iron treated iron-deficiency anemia of pregnancy and restored iron stores faster and more effectively than oral iron, with no serious adverse reactions.", "In the context of limited effectiveness of iron supplementation programs, intermittent iron supplementation is currently under debate as a possible alternative strategy that may enhance the effectiveness of operational programs. This field-based trial assessed the outcome of twice weekly iron supplementation compared to daily in Pakistan. A double-blind, randomized, clinical trial was conducted in Northern Pakistan. Anemic pregnant women (n = 191) were assigned to receive daily (200 mg ferrous sulfate) or twice weekly (2 x 200 mg ferrous sulfate) iron supplementation. Hemoglobin was measured at baseline and at 4-wk intervals for up to 12 wk. Serum ferritin was measured at baseline and 8 or 12 wk. Analysis was by intention to treat. The two groups did not differ in age, parity, sociodemographic characteristics, hemoglobin or serum ferritin concentrations at baseline. Women who received iron daily had a greater rise in hemoglobin compared with women who received iron twice weekly (17.8 +/- 1.8 vs. 3.8 +/- 1.2 g/L, P < 0.001). The serum ferritin concentrations increased by 17.7 +/- 3.9 microgram/L (P < 0.001) in the daily supplemented group and did not change in the twice weekly group. Daily iron supplementation remained superior to twice weekly supplementation after controlling initial hemoglobin Z-scores and duration of treatment. The body mass index (BMI) modified the effect of daily versus twice weekly iron supplementation. For every unit increase in BMI, the difference between the two treatment groups was reduced by 0.0014 (final hemoglobin Z-score; P = 0.027). We recommend continuation of daily iron supplementation as opposed to intermittent iron supplementation in pregnant women in developing countries.", "The aim of this study was to compare intravenous iron sucrose versus oral iron sulfate in anemia at 6 months of pregnancy.\n A random, prospective, open study with individual benefit was performed involving 50 patients with hemoglobin levels between 8 and 10 g/dL and a ferritin value of <50 microg/L. In the intravenous group (IV group), the iron dose was calculated from the following formula: Weight before pregnancy (kg) x (120 g/L - Actual hemoglobin [g/L]) x 0.24 + 500 mg. The oral group (PO group) received 240 mg of iron sulfate per day for 4 weeks. Treatment efficacy was assessed by measurement of hemoglobin and reticulocytes on days 8, 15, 21, and 30 and at delivery and of ferritin on day 30 and at delivery. The baby's birth weight and iron stores were noted. Results were expressed as median +/- interquartile range. Mann-Whitney and Wilcoxon tests were used for the analysis, with P <.05 considered significant.\n An increase in hemoglobin was observed, rising from 9.6 +/- 0.79 g/dL to 11.11 +/- 1.3 g/dL on day 30 in the IV group and from 9.7 +/- 0.5 g/dL to 11 +/- 1.25 g/dL on day 30 in the PO group (not significant). On day 30 (P <.0001) and at delivery (P =.01) ferritin was higher in the IV group. A mean higher birth weight of 250 g was noted in the IV group (not significant).\n Iron sucrose appears to be a treatment without serious side effects indicated in correction of pregnancy anemia or iron stores depletion.", "A comparative study was conducted to demonstrate the difference, if any, in effectiveness of treatment of iron deficiency anaemia in pregnancy with either iron dextran or ferrous sulphate. Sixty pregnant women with iron deficiency anaemia were assigned randomly to either group and treated for 6 weeks. The age and parity distributions with mean packed cell volumes (PCVs) and gestational age at onset of treatment in the two groups were comparable. Comparing the mean PCVs at week 2, week 4 and week 6 of treatment the iron dextran group recorded higher and statistically significant mean PCVs (P<0.001). Thirty-six per cent of patients in the iron dextran group compared to 3.3% in the oral iron group (P=0.004) had their anaemia corrected by the sixth week. No significant side effects accompanied the use of intramuscular iron dextran. It was concluded that iron dextran corrects iron deficiency anaemia faster than ferrous sulphate. Parenteral iron should be considered in pregnant woman with moderate and asymptomatic severe anaemia between gestation ages of 28 weeks and 34 weeks; this may reduce the frequency of blood transfusion both in the antenatal and postnatal periods in these patients." ]

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[ "Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial.", "Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial.", "Effect of pharmacological treatment of depression on A1C and quality of life in low-income Hispanics and African Americans with diabetes: a randomized, double-blind, placebo-controlled trial.", "Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial.", "Treating depression in diabetes patients: does a nurse-administered minimal psychological intervention affect diabetes-specific quality of life and glycaemic control? A randomized controlled trial.", "Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.", "Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients.", "Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: a double-blind randomised placebo controlled 6-month trial.", "A randomized trial of telephonic counseling plus walking for depressed diabetes patients.", "Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a single-blind randomised placebo controlled trial.", "Web-based depression treatment for type 1 and type 2 diabetic patients: a randomized, controlled trial.", "Glycemic control improvement through treatment of depression using antidepressant drugs in patients with diabetes mellitus type 1.", "Treatment of depression in type 2 diabetes with Fluoxetine or Citalopram?", "Psychotherapy intervention to reduce depressive symptoms in patients with diabetic foot syndrome." ]

[ "To evaluate the efficacy and safety of oral magnesium supplementation, with magnesium chloride (MgCl2), in the treatment of newly diagnosed depression in the elderly with type 2 diabetes and hypomagnesemia. Twenty-three elderly patients with type 2 diabetes and hypomagnesemia were enrolled and randomly allocated to receive either 50 mL of MgCl2 5% solution equivalent to 450 mg of elemental magnesium or Imipramine 50 mg daily during 12 weeks. Widowhood or divorce in the last six months, alcoholism, degenerative illnesses of the nervous central system, recent diagnosis of diabetes, previous or current treatment with antidepressants, chronic diarrhea, use of diuretics, and reduced renal function were exclusion criteria. Hypomagnesemia was defined by serum magnesium levels < 1.8 mg/dL and depression by Yasavage and Brink score > or = 11 points. The primary trial end point was the improvement of depression symptoms. At baseline, there were no differences by age (69 +/- 5.9 and 66.4 +/- 6.1 years, p = 0.39), duration of diabetes (11.8 +/- 7.9 and 8.6 +/- 5.7 years, p = 0.33), serum magnesium levels (1.3 +/- 0.04 and 1.4 +/- 0.04 mg/dL, p = 0.09), and Yasavage and Brink Score (17.9 +/- 3.9 and 16.1 +/- 4.5 point, p = 0.34) in the groups with MgCl2 and imipramine, respectively. At end of follow-up, there were no significant differences in the Yasavage and Brink score (11.4 +/- 3.8 and 10.9 +/- 4.3, p = 0.27) between the groups in study; whereas serum magnesium levels were significantly higher in the group with MgCl2 (2.1 +/- 0.08 mg/dL) than in the subjects with imipramine (1.5 +/- 0.07 mg/dL), p < 0.0005. In conclusion, MgCl2 is as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily.", "Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment. This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome.\n Sixty-eight diabetic patients with poor glycemic control, 28 of whom had active major depression (DSM-IIIR), completed a randomized, placebo-controlled, double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels (50-150 ng/ml). Depression improvement was determined with the Beck Depression Inventory; glucose control was measured by glycated hemoglobin levels. Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory.\n The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo (-10.2 vs -5.8, p = .03). Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects (p = .5). However, path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin. These findings were not explained by the relationships of nortriptyline treatment to weight change (r = -0.21, p = .31) or depression improvement to compliance with the protocol for self-monitoring of blood glucose (r = 0.01, p = .97).\n Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect. Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control, suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome.", "To determine whether pharmacological treatment of depression in low-income minorities with diabetes improves A1C and quality of life (QOL).\n This was a 6-month, randomized, double-blind, placebo-controlled trial. Patients were screened for depression using Whooley's two-question tool at a county diabetes clinic. Depression was confirmed (or not) with the Computerized Diagnostic Interview Survey (CDIS) software program, and the severity of depression was assessed monthly by the Hamilton Depression Scale (HAM-D). Depressed subjects with A1C levels >or=8.0% were randomly assigned to receive either sertraline or placebo. Diabetes care was provided by nurses following detailed treatment algorithms who were unaware of therapy for depression.\n A total of 150 subjects answered positively to at least one question on Whooley's questionnaire. The positive predictive value for depression diagnosed by CDIS was 69, 67, and 84% for positive answers to question 1 only, question 2 only, or both, respectively. Of the 89 subjects who entered the study, 75 completed. An intention-to-treat analysis revealed significant differences between baseline and 6 months in HAM-D and pain scores, QOL, and A1C and systolic blood pressure levels in both groups, with no differences between groups for the first three but a significantly greater decrease with sertraline in A1C and systolic blood pressure levels. Changes in HAM-D scores and A1C levels were significantly correlated in all subjects (P = 0.45 [P < 10(-6)]).\n In this low-income minority population, pharmacological treatment of depression significantly improved A1C and systolic blood pressure levels compared with placebo.", "Depression is prevalent in patients with diabetes. It is associated with poor glycemic control and is linked to an increased risk for diabetic complications. In this study, we assessed the efficacy of fluoxetine for depression in patients with diabetes.\n Sixty patients with diabetes (type 1, n = 26; type 2, n = 34) and major depressive disorder entered an 8-week randomized placebo-controlled double-blind trial. Patients were given daily doses of fluoxetine (up to 40 mg/day). The Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAMD) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission. GHb levels were obtained to monitor glycemic control.\n Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo (BDI, -14.0 vs. -8.8, P = 0.03; HAMD, -10.7 vs. -5.2, P = 0.01). The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group (66.7 vs. 37.0%, P = 0.03). Additionally, trends toward a greater rate of depression remission (48.1 vs. 25.9%, P = 0.09 per the HAMD) and greater reduction in GHb (-0.40 vs. -0.07%, P = 0.13) were observed in the fluoxetine group.\n Fluoxetine effectively reduces the severity of depression in diabetic patients. Our study demonstrated that after only 8 weeks, this treatment also produced a trend toward better glycemic control.", "The aim of this study was to examine whether a nurse-administered minimal psychological intervention for depressive symptoms improves diabetes-specific quality of life and glycaemic control in older persons with diabetes.\n Depression is common among persons with diabetes and may have a negative impact on diabetes. Interventions aimed at reducing depressive symptoms may positively influence diabetes-specific quality of life as well.\n A pragmatic, randomized controlled trial was carried out comparing the intervention with usual care among 208 Dutch primary care patients of ≥60 years with type 2 diabetes and co-occurring minor to moderate depression. Data on symptom distress and emotional distress were collected during 2003-2006, and haemoglobin A1c levels were obtained from general practices. Data were analysed using mixed model, repeated measures ANCOVAS. Hba1c was collected retrospectively from general practices between December 2006-February 2007. In July 2007 we retrieved some additional HbA1c data from the medical records of the university hospital.\n Only in higher-educated persons did the intervention have statistically significant effect on both emotional distress and symptom distress (DSC-R total score at 9 months P=0.001; PAID, 9 months P=0.03). Furthermore, we found an effect on symptom distress in men (9 months P=0.01), and on emotional distress in persons with a shorter diabetes duration (<7 years) (9 months P=0.04). A significant trend over time for haemoglobin A1c was found in favour of the intervention, with a statistically significant difference between groups after 9 months (P=0.02).\n The nurse-administered intervention had limited effects on diabetes-specific quality of life. As only certain subgroups benefited, ways of increasing effectiveness in other groups should be explored. The potentially beneficial effect on glycaemic control is encouraging and needs further research because of small numbers in the analysis.\n © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.", "Psychotherapy is the principal nonpharmacologic method for the management of depression, but its usefulness for depressed patients with diabetes remains unknown.\n To assess the efficacy of cognitive behavior therapy (CBT) for depression in patients with diabetes.\n Randomized, controlled trial.\n Referral-based academic medical center.\n 51 patients with type 2 diabetes and major depression.\n Patients were assigned either to a group that received 10 weeks of individual CBT or to a control group that received no specific antidepressant treatment. All patients participated in a diabetes education program to control for the effects of supportive attention and the possible influence of enhanced diabetes control on mood.\n Degree of depression was measured by using the Beck Depression Inventory; glycemic control was measured by using glycosylated hemoglobin levels. Outcomes were assessed immediately after treatment and 6 months after treatment.\n The percentage of patients achieving remission of depression (Beck Depression Inventory score < or = 9) was greater in the CBT group than in the control group: posttreatment, 85.0% of patients in the CBT group (17 of 20) compared with 27.3% of controls (6 of 22) achieved remission (difference, 57.7 percentage points [95% CI, 33 to 82 percentage points]) (P < 0.001); at follow-up, 70.0% of patients in the CBT group (14 of 20) compared with 33.3% of controls (7 of 21) achieved remission (difference, 36.7 percentage points [CI, 9 to 65 percentage points]) (P = 0.03). Post-treatment glycosylated hemoglobin levels were not different in the two groups, but follow-up mean glycosylated hemoglobin levels were significantly better in the CBT group than in the control group (9.5% compared with 10.9%; P = 0.03).\n The combination of CBT and supportive diabetes education is an effective nonpharmacologic treatment for major depression in patients with type 2 diabetes. It may also be associated with improved glycemic control.", "This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety, quality of life, disability, and metabolic control in type II diabetes mellitus (DM) patients.\n The patients were first applied the Hospital Anxiety-Depression Scale (HADS). After a psychiatric interview with patients who had scores above the cut-off point, those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 (SF-36), and the Brief Disability Questionnaire (BDQ) and HbA1c levels were measured. Patients were randomized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment. The patients were evaluated with the same scales at the 2(nd), 4(th), 6(th), and the 12(th) weeks.\n Both groups showed a statistically significant decrease in HDRS, HARS, and BDQ scores with comparison to the index assessment. At the end of treatment, though not statistically significant, a decrease was observed in HbA1c values of the fluoxetine-administered group.\n Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients. There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control.", "Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50-70 years.\n We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A1c(GHbA1c). Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale.\n Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA1c (mean difference = 0.59%-units, p = 0.018) and in SF-36 score (mean difference = 11.0 points, p = 0.039). However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred.\n This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub-threshold depression is likely to be modest and of short duration. Routine antidepressant prescription for patients with diabetes and sub-threshold depressive symptoms is not indicated.\n Current controlled trials ISRCTN55819922.", "Patients with diabetes and depression often have self-management needs that require between-visit support. This study evaluated the impact of telephone-delivered cognitive behavioral therapy (CBT) targeting patients' management of depressive symptoms, physical activity levels, and diabetes-related outcomes.\n Two hundred ninety-one patients with type 2 diabetes and significant depressive symptoms (Beck Depression Inventory scores ≥ 14) were recruited from a community-based, university-based, and Veterans Affairs health care systems. A manualized telephone CBT program was delivered weekly by nurses for 12 weeks, followed by 9 monthly booster sessions. Sessions initially focused exclusively on patients' depression management and then added a pedometer-based walking program. The primary outcome was hemoglobin A1c levels measured at 12 months. Blood pressure was a secondary outcome; levels of physical activity were determined by pedometer readings; depression, coping, and health-related quality of life were measured using standardized scales.\n Baseline A1c levels were relatively good and there was no difference in A1c at follow-up. Intervention patients experienced a 4.26 mm Hg decrease in systolic blood pressure relative to controls (P=0.05). Intervention patients had significantly greater increases in step counts (mean difference, 1131 steps/d; P=0.0002) and greater reductions in depressive symptoms (58% remitted at 12 mo vs. 39%; P=0.002). Intervention patients also experienced relative improvements in coping and health-related quality of life.\n This program of telephone-delivered CBT combined with a pedometer-based walking program did not improve A1c values, but significantly decreased patients' blood pressure, increased physical activity, and decreased depressive symptoms. The intervention also improved patients' functioning and quality of life.", "Depression is prevalent in people with type 2 diabetes and affects both glycemic control and overall quality of life. The aim of this trial was to evaluate the effect of the antidepressant paroxetine on metabolic control, quality of life and mental well-being in mildly depressed women with type 2 diabetes.\n We randomised 15 mildly depressed women with non-optimally controlled type 2 diabetes to a 10-week single-blind treatment with either paroxetine 20 mg per day or placebo. Primary efficacy measurements were glycemic control and quality of life. Glycosylated hemoglobin A1c (GHbA1c) was used as a measure of glycemic control. Quality of life was evaluated using RAND-36. Mental state was assessed using two clinician-rated scoring instruments, Hamilton's Anxiety Scale (HAM-A) and Montgomery-Asberg's Depression Rating Scale (MADRS), and a patient-rated scoring instrument, Beck's Depression Inventory (BDI).\n At the end of the study no significant difference between groups in improvement of quality of life was found. A trend towards a superior improvement in glycemic control was found in the paroxetine group (p = 0.08). A superior increase in sex-hormone-binding-globuline (SHBG) levels was evidenced in the paroxetine group (p = 0.01) as a sign of improved insulin sensitivity. There was also a trend for superior efficacy of paroxetine in investigator-rated anxiety and depression. This notion was supported by a trend for superior decrease of serum cortisol levels in the paroxetine group (p = 0.06).\n Paroxetine has a beneficial effect on measures of insulin sensitivity and may improve glycemic control. Larger studies of longer duration are needed to verify the benefits of paroxetine in type 2 diabetes. While waiting for more conclusive evidence it seems sensible to augment standard care of type 2 diabetes with paroxetine even in patients who do not fulfil routine psychiatric criteria for initiation of antidepressant drug treatment.", "Comorbid depression is common in patients with type 1 and type 2 diabetes, adversely affecting quality of life, diabetes outcomes, and mortality. Depression can be effectively treated with cognitive behavior therapy (CBT). The Internet is a new and attractive method for delivering CBT intervention on a large scale at relatively low costs. This study evaluated the effectiveness of Web-based CBT for depression treatment in adults with type 1 or type 2 diabetes, with minimal guidance.\n A randomized controlled trial was conducted in the Netherlands in 255 adult diabetic patients with elevated depressive symptoms. Primary outcomes were depressive symptoms. Secondary outcomes were diabetes-specific emotional distress and glycemic control. Assessments were at baseline, after treatment, and at the 1-month follow-up.\n The Web-based CBT was effective in reducing depressive symptoms by intention-to-treat analyses (P = 0.04, d = 0.29; clinical improvement 41% vs. 24% P < 0.001) and by per-protocol analyses (P < 0.001, d = 0.70; clinical improvement, 56% vs. 24% P < 0.001). The intervention reduced diabetes-specific emotional distress (P = 0.03) but had no beneficial effect on glycemic control (P > 0.05).\n Web-based CBT depression treatment is effective in reducing depressive symptoms in adults with type 1 and type 2 diabetes. In addition, the intervention reduces diabetes-specific emotional distress in depressed patients.", "Depression is a common disorder among diabetic patients and affects negatively the treatment of their basic disease. The aim of the study was to assess, whether antidepressant medication could positively influence glycemic control of diabetes type 1 in depressive or anxious patients.\n A six-month, double-blinded, randomized, placebo-controlled study was performed to investigate the reaction of type 1diabetic patients (n=21) to treatment of depression and anxiety symptoms using antidepressant drug sertraline. The patients were given sertraline (100 mg/day) or placebo. The evolution of mental change was assessed using Zung Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) along with development of somatic parameters commonly assessed in diabetic patients, especially glycosylated hemoglobin, insulin dose and body weight. The level of active substance in serum of the patients was also measured.\n Mental state improved at the level of statistical significance of p<0.001 in both patients using antidepressant and placebo. From somatic parameters, body weight and systolic blood pressure increased statistically significantly also in both groups of patients.\n The mental state of most patients who successfully completed the study improved regardless of the fact if they were using antidepressant or placebo. No statistically significant connections between the mental and somatic changes were found. This finding points out to the placebo effect of the medication, to the importance of a contact with patients, but also to the need to concentrate on their mental state.", "Comparing the antidepressant effects of Citalopram with Fluoxetine and their effect on glycemic control in diabetic patients.\n Forty patients attending the Diabetes Research Center in Kermanshah University of Medical Sciences, Kermanshah, Iran from September 2006 to October 2007 with type II diabetes and suffering from major depression were randomly assigned to 2 groups (n=20 per group) in a randomized controlled trial method. They received up to 40 mg/d of Fluoxetine or Citalopram. Twelve weeks after treatment, patients were reassessed in terms of severity of depression and diabetic status. The Beck Depression Inventory (BDI) and psychiatric interview were used to measure the severity of depression and follow up the patients. Glycosylated hemoglobin (HbA1c) levels and fasting blood sugar (FBS) was obtained to monitor glycemic control.\n After the 12-week treatment, both groups showed significant improvement in severity of depression, FBS, and HbA1c. There were no significant differences between the 2 groups in terms of improvement in depression and diabetic status.\n Fluoxetine and Citalopram can effectively reduce the severity of depression in diabetic patients without an adverse effect on glycemic control.", "Compared to the population as a whole, patients with diabetes mellitus suffer a significantly higher rate of depressive symptoms, especially when they develop complications. Psychotherapy treatments in diabetes mellitus can lead to improvements in both depressive symptoms and glycaemic control. The objective of this study was to investigate whether depressive symptoms can be reduced by psychotherapy treatment delivered as a joint interdisciplinary service to in-patients with diabetic foot syndrome and comorbid depression.\n Thirty in-patients with diabetic foot syndrome and comorbid depression were randomized to either an intervention group (n = 15) with supportive psychotherapy treatment or a control group (n = 15) that received only standard medical treatment. Patients completed a set of questionnaires at the beginning and end of treatment. These recorded sociodemographic variables, anxiety and depression (Hospital Anxiety and Depression Scale) and diabetes-related problems (Problem Areas in Diabetes Scale).\n Although the diabetic foot syndrome improved significantly in 75% of patients, the extent of depressive symptoms and anxiety reported by the control group did not decrease by the end of treatment. In contrast, in the intervention group, anxiety, depression and diabetes-related problems were all reduced. The extent of anxiety and depression was not, as had been anticipated, associated with the severity of the physical symptoms.\n These results indicate that psychotherapeutic intervention during in-patient treatment can have a positive influence on anxiety, depressive symptoms and diabetes-related problems in patients with diabetic foot syndrome." ]

[ "17101314", "18237866" ]

[ "A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis.", "Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children." ]

[ "Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis.\n We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 mug of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of </=1 eosinophil in all 400x fields in both the proximal and distal esophagus.\n Fifty percent of FP-treated patients achieved histologic remission compared with 9% of patients receiving placebo (P = .047). FP decreased esophageal eosinophil levels, with a more pronounced effect in nonallergic individuals (65.9 +/- 25.3 vs 1.4 +/- 1.1 eosinophils/high-power field in the proximal esophagus [P = .03] and 84.6 +/- 19.7 vs 19.6 +/- 12.9 eosinophils/high-power field in the distal esophagus [P = .04]). Resolution of vomiting occurred more frequently with FP than placebo (67% vs 27%; P = .04). FP-induced resolution of mucosal eosinophilia was associated with resolution of endoscopic findings, epithelial hyperplasia, younger age (P = .0003), shorter height (P = .002), and lighter weight (P = .02). Effective treatment with FP decreased the number of CD8(+) T lymphocytes and mast cells in both the proximal and distal esophagus (P < .05).\n Swallowed FP is effective in inducing histologic remission in eosinophilic esophagitis, with a more pronounced effect in nonallergic and younger individuals, especially in the proximal esophagus.", "Although eosinophilic esophagitis is recognized increasingly, outcome data guiding therapy are limited. We conducted a prospective randomized trial comparing oral prednisone (P) and swallowed fluticasone (F) for histologic and clinical response.\n Patients were randomized to receive P or F for 4 weeks, followed by an 8-week weaning protocol. Esophageal histology was evaluated at baseline and after 4 weeks of therapy. Clinical assessments were performed at weeks 0, 4, 12, 18, and 24.\n Eighty patients with eosinophilic esophagitis were enrolled: 40 in the P arm and 40 in the F arm. Histologic improvement was seen in 30 of 32 P and 34 of 36 F patients, with a greater degree of histologic improvement in the P group. All P and 35 of 36 F patients were free of presenting symptom(s) at week 4. Symptom relapse was seen in 45% of patients by week 24. Kaplan-Meier analysis showed no difference between P and F with regard to relapse rate (P = .7399). No significant difference in time to relapse was found between groups (P = .2529). Systemic adverse effects were noted in 40% of the P arm, whereas esophageal candidal overgrowth was seen in 15% of the F arm.\n Systemic and topical corticosteroids were effective in achieving initial histologic and clinical improvement. P resulted in a greater degree of histologic improvement, without evidence of an associated clinical advantage over F in terms of symptom resolution, relapse rates, or time to relapse. Symptom relapse was common to both groups upon therapy discontinuation, highlighting the need for maintenance treatment protocols." ]

[ "15353533", "12925845", "12824212", "11923489", "11923490", "15073677", "16139395", "15837236", "16107961", "15680454" ]

[ "Vaccination success rate and reaction profile with diluted and undiluted smallpox vaccine: a randomized controlled trial.", "Clonal vaccinia virus grown in cell culture as a new smallpox vaccine.", "Response to smallpox vaccine in persons immunized in the distant past.", "Dose-related effects of smallpox vaccine.", "Clinical responses to undiluted and diluted smallpox vaccine.", "Adverse events after smallpox immunizations are associated with alterations in systemic cytokine levels.", "Clinical and immunological responses to undiluted and diluted smallpox vaccine with vaccinia virus of Lister strain.", "A novel, cell culture-derived smallpox vaccine in vaccinia-naive adults.", "Clinical responses to smallpox vaccine in vaccinia-naive and previously vaccinated populations: undiluted and diluted Lancy-Vaxina vaccine in a single-blind, randomized, prospective trial.", "Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial." ]

[ "Additional smallpox vaccine doses are needed to augment current US national stockpile. Aventis Pasteur smallpox vaccine (APSV), initially manufactured in the 1950s from the New York Board of Health vaccinia strain in a frozen preparation, appears as effective as lyophilized vaccine but the effectiveness of diluted doses of APSV is unclear.\n To compare the vaccination success rate and the reaction profile of various APSV dilutions.\n A double-blind, randomized controlled trial of 340 healthy vaccinia-naive adults aged 18 to 32 years from 3 academic medical centers who were vaccinated with 1 of 3 strengths of APSV dilutions (undiluted, 1:5, and 1:10) between October 9, 2002, and February 24, 2003. Volunteers were followed up every 3 to 5 days until the vaccination site healed for bandage changes, vaccine response assessment, and adverse event evaluation, followed by 1- and 2-month clinic evaluations and 6-month telephone interview.\n Successful vaccination, defined by presence of a vesicle or pustule at the inoculation site 6 to 11 days postvaccination, and local and systemic reactions to vaccination.\n A total of 340 volunteers were vaccinated (vaccine dose: undiluted, n = 113; 1:5 dilution, n = 114; and 1:10 dilution, n = 113). Following vaccination, 99.4% (95% confidence interval [CI], 97.9%-99.9%) of all volunteers had successful vaccinations. Success rates did not differ between the dilution groups (undiluted, 100.0%; 95% CI, 96.8%-100.0%; 1:5 dilution, 98.2%; 95% CI, 93.8%-99.8%; 1:10 dilution, 100.0% 95% CI, 96.8%-100.0%; P =.33). Overall, 99.7% of volunteers reported at least 1 local symptom at the vaccination site, and 61.8% had axillary lymphadenopathy, 15.0% developed satellite lesions, and 7.6% developed a rash away from the vaccination site. Fever developed in 21.5%. No differences were noted in local or systemic reactions between the 3 dilution groups (P>.05 for each comparison). A total of 25% of volunteers missed scheduled duties due to vaccine-related symptoms.\n Even at diluted doses, APSV is an effective smallpox vaccine, allowing for expansion of the current stockpile. However, reactogenicity was not reduced with dilution of the vaccine and, as with other smallpox vaccines, may impair daily activities.", "Although the smallpox virus was eradicated over 20 years ago, its potential release through bioterrorism has generated renewed interest in vaccination. To develop a modern smallpox vaccine, we have adapted vaccinia virus that was derived from the existing Dryvax vaccine for growth in a human diploid cell line. We characterized six cloned and one uncloned vaccine candidates. One clone, designated ACAM1000, was chosen for development based on its comparability to Dryvax when tested in mice, rabbits and monkeys for virulence and immunogenicity. By most measures, ACAM1000 was less virulent than Dryvax. We compared ACAM1000 and Dryvax in a randomized, double-blind human clinical study. The vaccines were equivalent in their ability to produce major cutaneous reactions ('takes') and to induce neutralizing antibody and cell-mediated immunity against vaccinia virus.", "There is renewed interest in use of smallpox vaccine due to the potential for a bioterrorist attack. This would involve vaccinating health care workers who were previously vaccinated.\n To evaluate the use of diluted vaccinia virus in vaccination of previously vaccinated (non-naive) participants.\n Eighty non-naive participants, aged 32 to 60 years, were randomized in a single-blinded study to receive either undiluted or diluted (1:3.2, 1:10, or 1:32) doses of smallpox vaccine. A comparison group, aged 18 to 31 years, of 10 vaccinia-naive participants received undiluted vaccine. Participants were enrolled between April 1 and May 15, 2002, at the National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit at Saint Louis University, St Louis, Mo.\n Smallpox vaccine was administered by scarification using 15 skin punctures in the deltoid region of the arm.\n Presence of a major reaction, defined as a vesicular or pustular lesion or area of palpable induration surrounding a central lesion following vaccination, and measures of viral shedding and antibody titers.\n Initial vaccination resulted in a major reaction in 64 of 80 non-naive participants. Ninety-five percent of non-naive participants had major reactions in the undiluted group, 90% in the 1:3.2 dilution group, 81% in the 1:10 dilution group, and 52.6% in the 1:32 dilution group. All (n = 10) of the vaccinia-naive participants had major reactions. Compared with vaccinia-naive participants, non-naive participants had significantly smaller skin lesions (P =.04) and significantly less incidence of fever (P =.02). Preexisting antibody was present in 76 of 80 non-naive participants. Antibody responses were significantly higher and occurred more rapidly in the non-naive participants compared with the vaccinia-naive participants (P =.002 for day 28 and P =.003 for 6 months). Vaccinia-naive participants shed virus from the vaccination site 2 to 6 days longer and had significantly higher peak mean viral titers when compared with the non-naive participants (P =.002).\n Previously vaccinated persons can be successfully revaccinated with diluted (<or=1:10) smallpox vaccine. Fewer adverse reactions were observed in this study of non-naive participants when compared with events in vaccinia-naive participants, which may be due to immunologic memory.", "We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells.\n Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses.\n A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle.\n The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections.", "To evaluate the potential to increase the supply of smallpox vaccine (vaccinia virus), we compared the response to vaccination with 10(8.1), 10(7.2), and 10(7.0) plaque-forming units (pfu) of vaccinia virus per milliliter.\n In this randomized, single-blind, prospective study, 680 adults who had not been previously immunized were inoculated intradermally with undiluted vaccine (mean titer, 10(8.1) pfu per milliliter), a 1:5 dilution, or a 1:10 dilution of vaccinia virus with use of a bifurcated needle, and the site was covered with a semipermeable dressing. Subjects were monitored for vesicle formation (an indicator of the success of vaccination) and adverse events for 56 days after immunization.\n Success rates did not differ significantly among the groups and ranged from 97.1 to 99.1 percent after the first vaccination. Both the undiluted and diluted vaccines were reactogenic. In addition to the formation of pustules, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills consistent with the presence of an acute viral illness. Generalized and localized rashes, including two cases of erythema multiforme, were also observed.\n When given by a bifurcated needle, vaccinia virus vaccine can be diluted to a titer as low as 10(7.0) pfu per milliliter (approximately 10,000 pfu per dose) and induce local viral replication and vesicle formation in more than 97 percent of persons.", "The immunization of healthy adults with vaccinia virus (VV) induces a protective response against smallpox in most individuals but is also reactogenic in a significant number of vaccinees. The immunological mechanisms underlying the protective response or adverse events in humans are not well defined. Although cytokines contribute to antiviral immunity and, in some cases, cause systemic adverse effects, their role in the human response to VV is unknown. We investigated the effect of smallpox immunization on systemic cytokine concentrations in a cohort of VV-naive individuals. We found that smallpox immunization induces an interferon (IFN)- gamma -dominant response in the systemic compartment 1 week after immunization, with concentrations returning to baseline during convalescence. The level of IFN- gamma induced was not affected by the dilution of vaccine used. We also found that particular adverse events correlated with systemic cytokine patterns, which suggests a role for these molecules in the pathogenesis of adverse events.", "The potential to increase the supply of vaccine by diluting the vaccinia virus of Lister strain to face possible bioterrorism with smallpox was evaluated. Vaccinia-naïve subjects (n=97) were randomized to receive either undiluted or diluted (1:5, 1:10) vaccine, and previously vaccinated subjects (n=122) were randomized to receive either undiluted or diluted (1:10, 1:30) vaccine. Except two subjects who received 1:30 diluted vaccine, the vaccination of all subjects was successful clinically. All subjects had significant vaccinia-specific T cell and antibody responses. The diluted vaccine was not associated with decreased local or systemic reactions, lower T cell responses, or higher antibody titers when compared with undiluted vaccine. Here we show the diluted vaccine of Lister strain can be used in vaccinia-naïve subjects and previously vaccinated subjects if viral titer > or =10(8) and 10(7.5) pfu/mL after dilution, respectively. The reactogenicity of vaccinia virus may not be a dose-dependent response.", "Despite the eradication of smallpox as a naturally occurring disease, concern persists over its potential use as a bioterrorist agent. The development of a new-generation smallpox vaccine represents an important contribution to a cogent biodefense strategy. We conducted a phase 2 randomized, double-blind, controlled trial at four sites in the United States to determine whether a clonal smallpox vaccine manufactured in cell culture, ACAM2000, is equivalent to the standard calf-lymph vaccine, Dryvax, in terms of cutaneous response rate, antibody responses and safety. Subjects received either Dryvax or one of four dose levels of ACAM2000 administered percutaneously using a bifurcated needle. All subjects in the highest ACAM2000 dose group and the Dryvax group experienced a successful vaccination. Dilution doses of ACAM2000 were associated with success rates below the 90% threshold established for efficacy. There were no differences in the proportion of subjects who developed neutralizing antibody: 94% in the highest ACAM2000 dose group (95% CI, 84-99) and 96% in the Dryvax group (95% CI, 86-100). No significant differences were seen between the effective ACAM2000 and Dryvax groups regarding the occurrence of adverse events. One subject who received ACAM2000 developed myopericarditis. In healthy, primary vaccines ACAM2000 has a similar vaccination success rate, antibody response, and safety profile to Dryvax.", "We conducted a single-blind, randomized trial of 2 dilutions (1:1 or 1:10) of Lancy-Vaxina vaccine (Berna Biotech) in vaccinia-naive persons (n=36) and persons previously vaccinated >25 years ago (n=76). All vaccinees responded successfully to the vaccination. There were no significant differences in the size of the skin lesions, the number of adverse events, the amount of viral shedding, or the level of antibody responses between the undiluted (n=56) and diluted (n = 56) vaccine groups. Compared with vaccinia-naive persons, previously vaccinated persons exhibited significantly smaller and more rapidly evolving skin lesions and fewer adverse events. Previously vaccinated persons had significantly higher neutralizing antibody levels before the administration of the study vaccine than vaccinia-naive persons, and viral shedding from lesions in previously vaccinated persons was lower and diminished more rapidly than from lesions in vaccinia-naive persons.", "US government organisations have identified the need for a new smallpox vaccine to replenish limited stocks of the approved, calf-lymph derived vaccine, the manufacture of which is no longer acceptable. We aimed to compare the safety and immunogenicity of the new cell-cultured smallpox vaccine (CCSV) to that of the calf-lymph derived vaccine (as a positive control) in 350 healthy, adult volunteers.\n We did a randomised controlled study at the University of Kentucky Medical Center. We randomised 150 vaccinia-naive volunteers, aged 18-30 years, and 100 vaccinia-non-naive people, aged 32-65 years, to equivalent doses of either CCSV or test vaccine (2.5x10(5) plaque-forming units) by 15 puncture scarification in double-blind fashion. Immunogenicity was assessed by pock formation (take rate), humoral immune response by plaque-reduction neutralisation titres, and cellular immune response by vaccinia-specific, interferon-gamma T-cell quantification, cytotoxicity, and T-cell proliferation response. A further 100 vaccine-naive individuals, aged 18-30 years, received one of five doses of CCSV (undiluted, diluted 1 in 5, 1 in 10, 1 in 25, and 1 in 50) in single-blind fashion. Routine laboratory assessments, physical examinations, and recording of adverse events were done to assess vaccine safety. The primary endpoints were safety and reactogenicity (take rate) of CCSV.\n 349 (99.7%) of 350 volunteers developed pock lesions; one vaccinia-naive individual who received a 1 in 25 dilution of CCSV did not. The rate of adverse events related to vaccine and the extent of humoral and cellular immune responses did not differ between the vaccine groups in vaccinia-naive or non-naive people. CCSV was immunogenic in vaccine-naive volunteers at a dose 50 times lower than that approved for Dryvax.\n CCSV seems to be a safe and immunogenic alternative to calf-lymph derived vaccine for both vaccinia-naive and non-naive people." ]

[ "3925176", "3646182", "9644707", "11310690", "373560", "3114506", "6708261", "10203434", "15357156", "3932250", "10432161", "2878025" ]

[ "A randomized trial on the effect of tubing changes on hub contamination and catheter sepsis during parenteral nutrition.", "Intravenous tubing containing burettes can be safely changed at 72 hour intervals.", "Changing i.v. administration sets: is 48 versus 24 hours safe for neutropenic patients with cancer?", "Optimal frequency of changing intravenous administration sets: is it safe to prolong use beyond 72 hours?", "Contamination of intravenous infusion fluid: effects of changing administration sets.", "Prospective study of replacing administration sets for intravenous therapy at 48- vs 72-hour intervals. 72 hours is safe and cost-effective.", "Intravenous tubing with burettes can be safely changed at 48-hour intervals.", "Changing parenteral nutrition administration sets every 24 h versus every 48 h in newborn infants.", "Routine changing of intravenous administration sets does not reduce colonization or infection in central venous catheters.", "The relationship between intravenous fluid contamination and the frequency of tubing replacement.", "A randomized trial of 72- versus 24-hour intravenous tubing set changes in newborns receiving lipid therapy.", "Contamination of intravenous infusion systems--the effect of changing administration sets." ]

[ "In previous studies the contamination of the catheter hub was found to be a common portal of entry for bacteria causing catheter-related sepsis. Since hub manipulations during tubing changes may increase the risk of contamination, a prospective trial was conducted to find out the effects of the frequency of tubing replacements on hub colonization and catheter sepsis rates. The results were compared with those obtained during an outbreak of coagulase negative staphylococci septicemia. Fifty-two patients were randomly allocated into two groups. Group A (n = 20) had the line changes every 2 days while group B (n = 32) had it replaced every 4 days. When the catheter was removed, the catheter tip and the hub were cultured by a quantitative method. Sterile, colonized, or infected hubs were equally distributed in both groups (A: 80, 15, and 5% vs B: 84, 6, and 10%). There were three episodes of catheter sepsis, one in group A and one in group B due to hub infection, and one in group B due to hematogenous seeding of the catheter tip. There were significant (p less than 0.001) differences between the trial and the historic series in respect to rates of hub colonization infection (19 vs 50%) and catheter sepsis (5.7 vs 40%). Delaying tubing changes does not increase catheter sepsis or hub contamination rates and, together with adequate hub protection, has proved to be a valuable factor in controlling an outbreak of catheter sepsis due to the coagulase negative staphylococci.", "No studies testing the safety of changing intravenous systems containing in-line burettes at 72 hours in an intensive care setting have been performed. Patients entering a medical or surgical intensive care unit were alternatively assigned to have any line with an in-line burette changed at either 48 hour (105 patients) or 72 hour (65 patients) intervals. Daily quantitative cultures with a 2 ml aliquot of burette fluid were obtained. Contaminated burette fluid was detected in 60 of 1181 (5.0%, 95% confidence interval, 3.7% to 6.3%) samples from the burettes changed at 48 hour intervals, and in 40 of 901 (4.4%, 95% confidence interval, 3.0% to 5.8%) samples from 72 hour interval burettes. Significant bacterial contamination of burette fluid, defined as ten or more colonies per milliliter, occurred in only seven (0.6%) cultures from patients in the 48 hour interval group compared with only three (0.3%) cultures in the 72 hour group. None of the contaminated burette fluids was associated with a primary bacteremia. Change of in-line burettes in patients in intensive care at 72-hour intervals is safe and should result in substantial cost savings to hospitals.", "To examine the effects of changing i.v. administration sets at 48 versus 24 hours on the incidence of infusion-related septicemia in neutropenic patients with cancer.\n Prospective, randomized clinical trial with repeated measures.\n Large urban cancer center.\n 50 adult inpatients with a primary diagnosis of hematologic malignancy, breast cancer, or testicular cancer or who were receiving a stem cell transplant.\n Subjects were assigned randomly to have their i.v. sets changed every 48 or 24 hours. Subjects continued in the study for a maximum of five measurements, until they were no longer neutropenic, or until transferred or discharged from the hospital.\n Rates of infusate colonization, microorganisms identified, incidence of infusion-related septicemia.\n Colonized infusate was detected in 18 (5%) of 413 i.v. sets; 9 (5%) of 177 sets were changed at 48 hours, and 9 (4%) of 236 sets were changed at 24 hours (p > 0.05). A trend toward increased colonization of i.v. sets used to administer parenteral nutrition (19%) and, to a lesser extent, electrolytes (9%) was identified in the 48-hour group. Coagulase-negative staphylococci were the most frequently isolated microorganisms in the i.v. infusate. Similar organisms were isolated from blood cultures and administration sets, however, no subject had identical organisms isolated from both i.v. infusate and blood cultures. No subject with colonized infusate developed infusion-related septicemia.\n No difference existed in the incidence of colonization or infusion-related septicemia between subjects whose i.v. administration sets were changed at 48 versus 24 hours.\n Changing i.v. administration sets every 48 hours is recommended. Exceptions to this include i.v. administration sets used to administer blood products and total parenteral nutrition.", "To determine the safety and cost-effectiveness of replacing the intravenous (IV) tubing sets in hospitalized patients at 4- to 7-day intervals instead of every 72 hours.\n Prospective, randomized study of infusion-related contamination associated with changing IV tubing sets within 3 days versus within 4 to 7 days of placement.\n A tertiary university cancer center.\n Cancer patients requiring IV infusion therapy were randomized to have the IV tubing sets replaced within 3 days (280 patients) or within 4 to 7 days of placement (232 patients). Demographic, microbiological, and infusion-related data were collected for all participants. The main outcome measures were infusion- or catheter-related contamination or colonization of IV tubing, determined by quantitative cultures of the infusate, and infusion- or catheter-related bloodstream infection (BSI), determined by quantitative culture of the infusate in association with blood cultures in febrile patients.\n The two groups were comparable in terms of patient and catheter characteristics and the agents given through the IV tubing. Intent-to-treat analysis demonstrated a higher level of tubing colonization in the 4- to 7-day group versus the 3-day group (median, 145 vs 50 colony-forming units; P=.02). In addition, there were three episodes of possible infusion-related BSIs, all of which occurred in the 4- to 7-day group (P=.09). However, when the 84 patients who received total parenteral nutrition, blood transfusions, or interleukin-2 through the IV tubing were excluded, the two groups had a comparable rate of colonization (0.4% vs 0.5%), with no catheter- or infusion-related BSIs in either group.\n In patients at low risk for infection from infusion- or catheter-related infection who are not receiving total parenteral nutrition, blood transfusions, or interleukin-2, delaying the replacement of IV tubing up to 7 days may be safe, as well as cost-effective", "Daily change of intravenous (i.v.) infusion administration sets has been recommended by the Center for Disease Control since 1973 to reduce the risk of infusion bacteremia. To evaluate this recommendation, we undertook a prospective, randomized, controlled trial that compared the rates of i.v.-associated bacteremia, in-use i.v. fluid contamination, and phlebitis in 300 patients whose administration sets were changed every 24 h with those in 300 patients whose administration sets were changed every 48 h. No i.v.-associated bacteremia occurred. Twelve of 600 infusions (2%) had positive infusion-fluid cultures: five in one group and seven in the other. Both groups had comparable rates of phlebitis. In this study population with low rates of fluid contamination, no benefit accrued from changing the administration sets every 24 h instead of every 48 h. In hospitals with low rates of fluid contamination, the routine changing of i.v. administration sets every 48 h will result in substantial financial savings.", "We prospectively studied the safety of replacing intravenous delivery systems, including those used in total parenteral nutrition, at 72- compared with 48-hour intervals in 487 patients. Although the prevalence of contamination of intravenous fluid was higher in administration sets replaced at 72-hour intervals (10/664, 1.5%) than in sets replaced every 48 hours (6/710, 0.8%), the difference is not statistically significant. Contamination in both groups was almost exclusively with small numbers of coagulase-negative staphylococci (range, 1 to 27 colony-forming units/mL); no contaminated infusion was associated with clinical signs of sepsis or concordant bacteremia. Contaminants were recovered less frequently from peripheral venous infusions (0.6%) than from infusions used for central venous access or hemodynamic monitoring (1.5%) or total parenteral nutrition (3.6%); infusions in an intensive care unit were more frequently contaminated (2.5%) than infusions on medical and surgical wards (0.9%). These data indicate that extrinsic contamination of intravenous fluid is a rare cause of endemic nosocomial septicemia, and for most infusions it is unnecessary to routinely replace delivery systems more frequently than every 72 hours.", "No studies of safety in changing intravenous systems containing in-line burettes at 48 hours in an intensive care setting have been performed. Patients entering a surgical intensive care unit were alternatively assigned to have any line with an in-line burette changed at either 24-hour (64 patients) or 48-hour (59 patients) intervals. Daily quantitative cultures with a 2-mL aliquot of burette fluid were obtained. Contaminated burette fluid was detected in nine of 452 (2.0%; 95% confidence interval, 0.7% to 3.3%) samples from 24-hour interval burettes and in nine of 224 (4.0%; 95% confidence interval, 1.4% to 6.6%) samples from 48-hour interval burettes. Bacterial contamination of burette fluid with ten or more colonies per milliliter occurred in only five (1.1%) cultures from patients in the 24-hour interval group compared with only two cultures (0.9%) in the 48-hour group. None of the contaminated burette fluids was associated with primary bacteremia. Change of in-line burettes in intensive care at 48-hour intervals is safe and should result in substantial cost savings.", "To determine whether changing total parenteral nutrition fluid administration sets (TAS) every 48 h rather than every 24 h results in a greater infusate contamination rate.\n Prospectively, 166 infants were assigned at random to have TAS changed either every 24 h or every 48 h. Samples of the infusate were cultured to determine contamination rates of the infusate in the sets and were tested from 149 of these infants. TAS was replaced every 24 h in the control group, and 445 amino acid plus dextrose solutions (AADS) and 449 lipid emulsions samples were taken for bacterial culture. Fungal cultures were also performed on 449 samples. The study group had TAS replaced every 48 h, and 454 samples of AADS were cultured for bacteria. The numbers of lipid emulsion samples sent for bacterial culture and fungal culture were 449 and 440, respectively. Information on type of intravenous access device, administration of antibiotics and blood cultures was also collected.\n There was no difference in bacterial contamination rates for AADS or lipid emulsion from TAS changed every 24 or 48 h (c2, P>0.05). Lipid emulsion sampled from the 24 h group showed a statistically significant higher rate of fungal contamination than specimens from the 48 h group (P<0.01).\n Changing TAS every 48 h versus 24 h does not increase the contamination rate of infusate in newborns.", "To determine the effect of routine intravenous (IV) administration set changes on central venous catheter (CVC) colonization and catheter-related bacteremia.\n Prospective, randomized, controlled trial.\n Eighteen-bed intensive care unit (ICU) in a large metropolitan hospital.\n Two hundred fifty-one patients with 404 chlorhexidine gluconate and silver sulfadiazine-coated multi-lumen CVCs.\n CVCs inserted in the ICU and in situ on day 4 were randomized to have their IV administration sets changed on day 4 (n = 203) or not at all (n = 201). Use of fluid containers and blood product administration sets was limited to 24 hours. CVCs were removed when not required, infection was suspected, or in place on day 7. Catheter cultures were performed on removal by blinded laboratory staff. Catheter-related bacteremia was diagnosed by a blinded intensivist using strict definitions. Data were collected regarding catheter duration, site, Acute Physiology and Chronic Health Evaluation (APACHE) II score, patient age, diagnosis, hyperglycemia, hypoalbuminemia, immune status, number of fluid containers and IV injections, and administration of propofol, blood, total parenteral nutrition, or lipid infusion.\n There were 10 colonized CVCs in the group receiving a set change and 19 in the group not receiving one. This difference was not statistically significant on Kaplan-Meier survival analysis. There were 3 cases of catheter-related bacteremia per group. Logistic regression found that burns diagnosis and increased ICU stay significantly predicted colonization.\n IV administration sets can be used for 7 days in patients with short-term, antiseptic-coated CVCs.", "Medical patients receiving IV therapy were randomly assigned to one of two IV tubing change groups. One group had a 48-hour tubing change and the other had no tubing change for the remainder of the cannula placement. A daily IV fluid specimen was processed microbiologically. To complete the study, a minimum of 3 continuous days of therapy and three fluid specimens was required. There were two contaminated specimens, one in each tubing change group. The contamination rate in the 48-hour change group was 0.87% and 0.96% in the no change group. The rate difference of 0.09% has a 95% confidence interval (-0.035 to +0.036) which includes zero. Survival analysis also revealed no significant difference in the cumulative probability of survival, however the mean duration of continuous tubing use of 4.3 days in the no change group and 1.8 days in the 48 hour change group were significantly different (p less than 0.05). The cumulative probability of surviving contamination free was 0.988 in the 48-hour group and 0.987 in the no-change group. We conclude that it is safe to change IV tubing at intervals up to but not exceeding 4 days.", "To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals.\n Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets.\n A 35-bed, teaching, referral, neonatal intensive-care unit (NICU).\n All neonates admitted to the NICU for whom intravenous lipid was ordered.\n Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access.\n During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia.\n Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate.", "Intravenous administration sets were changed at varying time intervals between every 24 h and 120 h in 387 patients. The rates of intraluminal contamination of the cannulae and of local inflammation were measured in relation to the time interval between changing sets. There was no correlation between phlebitis and intraluminal contamination, but a significant association was found between phlebitis and fever, infusion of potassium at greater than 10 mmol l-1, Venflon type 140 and infusion of blood or intralipid. No correlation was found between septicaemia and intraluminal contamination of the infusion systems. Contamination of cannulae increased slightly with time, but this was not statistically significant. We conclude that there will be no clinical benefit by daily changing of administration sets, compared with changing up to every fifth day." ]

[ "21889410" ]

[ "Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial." ]

[ "Efficacious and safe monotherapy options are needed for adult patients with newly diagnosed epilepsy. As an adjunctive treatment for partial seizures, pregabalin compares favourably with lamotrigine and is an effective, approved treatment. We studied the efficacy and safety of pregabalin as monotherapy, using a design that complied with European regulatory requirements and International League Against Epilepsy guidelines.\n This phase 3, double-blind, randomised, non-inferiority study compared the efficacy and tolerability of pregabalin and lamotrigine monotherapy in patients with newly diagnosed partial seizures at 105 centres, mostly in Europe and Asia. Randomisation to treatment groups (1:1 ratio) was by a computer-generated pseudorandom code (random permuted blocks), with patients sequentially assigned numbers by telephone. Investigators, site staff, and patients were masked to the assigned treatment. After randomisation, patients were titrated to either 75 mg oral pregabalin or 50 mg oral lamotrigine twice daily during a 4-week dose-escalation phase, followed by a 52-week efficacy assessment phase during which the daily dose could be increased as needed to a maximum of 600 mg and 500 mg, respectively. The primary efficacy endpoint was the proportion of patients who remained seizure-free for 6 or more continuous months during the efficacy assessment phase; analysis included all patients who were randomly assigned to treatment groups and received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT00280059.\n 660 patients were randomly assigned to treatment groups (330 pregabalin, 330 lamotrigine), of whom 622 entered the efficacy assessment phase (314 pregabalin, 308 lamotrigine). Fewer patients in the pregabalin group than in the lamotrigine group became seizure-free for 6 or more continuous months (162 [52%] vs 209 [68%]; difference in proportion, -0·16, 95% CI -0·24 to -0·09). The overall incidence of adverse events was similar between the groups and consistent with that in previous studies; dizziness (55 [17%] vs 45 [14%] patients), somnolence (29 [9%] vs 14 [4%]), fatigue (27 [8%] vs 19 [6%]), and weight increase (21 [6%] vs 7 [2%]) were numerically more common in the pregabalin group than in the lamotrigine group.\n Pregabalin has similar tolerability but seems to have inferior efficacy to lamotrigine for the treatment of newly diagnosed partial seizures in adults. Inferior efficacy of pregabalin might have been attributable to limitations in the study design, as treatment doses might have not been optimised adequately or early enough.\n Pfizer Inc.\n Copyright © 2011 Elsevier Ltd. All rights reserved." ]

[ "20565316", "9377282", "9828778", "14507756", "15887725", "3281706", "20547942", "3311988", "21105974" ]

[ "Topical amphotericin B and subconjunctival injection of fluconazole (combination therapy) versus topical amphotericin B (monotherapy) in treatment of keratomycosis.", "Trial of chlorhexidine gluconate for fungal corneal ulcers.", "Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh.", "A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis.", "Efficacy of topical and systemic itraconazole as a broad-spectrum antifungal agent in mycotic corneal ulcer. A preliminary study.", "Topical silver sulphadiazine--a new drug for ocular keratomycosis.", "Comparison of natamycin and voriconazole for the treatment of fungal keratitis.", "Silver sulphadiazine in the treatment of mycotic keratitis.", "Voriconazole versus natamycin as primary treatment in fungal corneal ulcers." ]

[ "The aim of the study was to compare the use of combination therapy of topical amphotericin B (0.5 mg/mL) eye drops together with subconjunctival injection of fluconazole (2 mg/mL) with the use of topical amphotericin B (0.5 mg/mL) eye drops alone in dealing with cases of fungal keratitis.\n The study was performed in the Ophthalmology Department, Zagazig University and included 48 eyes of 48 patients who presented clinically with fungal keratitis. Laboratory investigations were performed, including direct microscopy of corneal smear using gram staining and culture of corneal specimens using Saboraud agar media and bacterial agar media. According to laboratory results, cases were classified into 2 groups: group 1 comprising 24 eyes treated by a combination therapy of topical amphotericin B eye drops (0.5 mg/mL) with subconjunctival injection of fluconazole (2 mg/mL) and group 2 comprising 24 eyes treated by topical amphotericin B eye drops (0.5 mg/mL) alone.\n Direct corneal smear for all 48 eyes included in the study revealed 18 eyes (38%) with positive fungal spores, 3 of them (6%) with gram-positive bacterial infection. Fungal culture of corneal specimens revealed positive result in 36 eyes (75%), including the positive corneal smear cases showing Candida in 12 eyes and filamentous fungi in 24 eyes. Treatment by a combination therapy in group 1 revealed statistically significant result (P < 0.05) of healing of corneal ulcers in 20 eyes (83%), with a mean duration of healing of 31 days (standard deviation [SD] +/-3), in comparison to group 2 with monotherapy, which revealed 16 eyes (67%), with a mean duration of healing of 37 days (SD +/-2).\n Combination therapy of topical amphotericin B eye drops with subconjunctival injection of fluconazole was more efficient (according to the percentage and the duration of healing of the ulcers) than the use of topical amphotericin B eye drops alone in dealing with cases of fungal keratitis--it may be contributed to the broad spectrum of the antifungal agents of the combination therapy than the monotherapy.", "Suppurative corneal ulcers due to filamentous fungi are a serious and intractable problem in many tropical developing countries. In vitro studies and a small pilot study have shown that chlorhexidine gluconate is effective. The aim was to establish the optimum concentration which would be appropriate to use in a larger randomized clinical trial.\n A masked randomized clinical trial of three concentrations of chlorhexidine compared with natamycin 5% was carried out in consecutive patients with established corneal ulcers shown by microscopy to contain fungal hyphae and later proven to be culture positive. Topical treatments were applied 1/2-hourly to 2-hourly for up to 5 days, with reduced frequency thereafter, and all patients were re-assessed at 21 days.\n Of 60 patients entered in the trial, 2 were lost to follow-up, and 12 were classified as 'severe' with little prospect of recovery. At 5 days the response was related to the concentration of chlorhexidine, with 0.2% giving the best results. Compared with the response to natamycin as the referent, the relative efficacy was 1.17 with chlorhexidine 0.05%, 1.43 with 0.1%, and 2.00 with 0.2%. The superiority of 0.2% chlorhexidine over natamycin was statistically significant (relative efficacy 2.20, p = 0.043) in patients not having had prior antifungal treatment.\n This preliminary study justifies further trials of chlorhexidine as a primary treatment for fungal corneal ulcers in circumstances where specific antifungal agents are not available.", "The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis.\n Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, \"treatment failure\" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial.\n 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment.\n Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.", "To compare 2% econazole and 5% natamycin in the management of fungal keratitis.\n A randomised clinical trial was performed using 2% econazole or 5% natamycin as the two treatment arms on patients presenting with culture positive fungal keratitis to the cornea service at Aravind Eye Care System, Madurai, India.\n 116 patients were recruited, and 112 continued in the study. There were no significant differences between the two arms at baseline or for success (defined as a healed or healing ulcer) at final visit (p = 0.79).\n 2% Econazole appears to be as effective as 5% natamycin for the management of fungal keratitis.", "To evaluate the efficacy of topical (1%) and systemic itraconazole against common fungi such as Aspergillus and other filamentous fungi that cause mycotic corneal ulcer.\n A prospective randomised, controlled study was done in 54 clinically suspected cases of fungal keratitis of which 44 were culture proven. Half the cases (n=27) with superficial involvement were treated with only topical itraconazole (1%) and the other half were treated with both topical and systemic itraconazole.\n Aspergillus, Penicillium and Fusarium were the most common fungi isolated. The ulcer resolved in 42 eyes (77%) and 12 eyes (23%) did not respond well to treatment. Four of 12 non-responding eyes were caused by Fusarium species.\n Itraconazole, given either topically or systemically, is effective in treating mycotic corneal ulcers.", "The efficacy of silver sulphadiazine in human keratomycosis has not been evaluated so far. Encouraged by the success of an earlier experimental trial, a prospective, controlled, randomised double masked clinical study was designed to evaluate the efficacy of 1% silver sulphadiazine ophthalmic ointment in 20 eyes of mycotic keratitis. Miconazole 1% was used for comparative evaluation in another 20 eyes. Silver sulphadiazine had a higher success rate (80% vs 55%) than miconazole. It had broad antifungal activity and was found to be effective in fusarium keratitis. Absence of side effects, economy, and its efficacy in deeper and extensive lesions were additional advantages. It is concluded from this study that silver sulphadiazine is a safe and effective broad spectrum antifungal agent which can be used for the treatment of human keratomycosis.", "To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis.\n The multicenter, double-masked, clinical trial included 120 patients with fungal keratitis at Aravind Eye Hospital in India who were randomized to receive either topical natamycin or topical voriconazole and either had repeated scraping of the epithelium or not.\n The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months. Other outcomes included scar size, perforations, and a subanalysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400.\n Compared with those who received natamycin, voriconazole-treated patients had an approximately 1-line improvement in BSCVA at 3 months after adjusting for scraping in a multivariate regression model but the difference was not statistically significant (P = .29). Scar size at 3 months was slightly greater with voriconazole after adjusting for scraping (P = .48). Corneal perforations in the voriconazole group (10 of 60 patients) were not significantly different than in the natamycin-treated group (9 of 60 patients) (P >.99). Scraping was associated with worse BSCVA at 3 months after adjusting for drug (P = .06). Patients with baseline BSCVA of 20/40 to 20/400 showed a trend toward a 2-line improvement in visual acuity with voriconazole (P = .07).\n Overall, there were no significant differences in visual acuity, scar size, and perforations between voriconazole- and natamycin-treated patients. There was a trend toward scraping being associated with worse outcomes. Application to Clinical Practice The benefit seen with voriconazole in the subgroup of patients with baseline visual acuity of 20/40 to 20/400 needs to be validated in a confirmatory clinical trial. Trial Registration clinicaltrials.gov Identifier: NCT00557362.", "nan", "To evaluate the efficacy of topical 1% voriconazole versus 5% natamycin in treatment of fungal corneal ulcers.\n A prospective, randomized pilot study in a tertiary care hospital.\n Thirty patients of microbiologically proven fungal keratitis divided randomly in two groups of 15 patients each.\n Two groups were treated with either 5% natamycin (group A) or 1% voriconazole (group B) topically as a primary treatment for fungal keratitis. The mean size, depth of infiltrate and LogMAR visual acuity at presentation were comparable in both groups (P > 0.05). Patients were followed up for minimum of 10 weeks or till complete resolution of ulcer, whichever was later. Cultures to identify the causative organisms were performed.\n Time of resolution of the ulcer.\n Twenty-nine of the total 30 patients showed complete resolution. Average time of resolution and gain in LogMAR visual acuity was 24.3 days and 1.12 in group A and 27.2 days and 0.77 in group B. These were comparable in the two groups (P > 0.05%). Aspergillus spp. (40%) and Curvularia spp. (30.0%) were found to be most common isolates.\n Topical 1% voriconazole was found to be safe and effective drug in primary management of fungal keratitis, its efficacy matching conventional natamycin. There was no added advantage of using topical 1% voriconazole over topical natamycin as primary treatment in fungal keratitis.\n © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists." ]

[ "7710583" ]

[ "Quasistatic volume-pressure curve to predict the effects of positive end-expiratory pressure on lung mechanics and gas exchange in neonates ventilated for respiratory distress syndrome." ]

[ "The shape of the volume-pressure (V/P) curve indicates alveolar collapse if it is convex to the pressure axis and indicates overdistension if it is concave. Positive end-expiratory pressure (PEEP) should either improve or decrease compliance and oxygenation in neonates ventilated for respiratory distress syndrome (RDS), depending on predominance of either alveolar collapse or overdistension. To test this hypothesis, we determined quasistatic V/P curves in 13 preterm neonates and characterized their shape by an alveolar distension index (ADI) at PEEP levels of 2, 4, and 6 cm H2O. We calculated the ADI dividing the V/P ratio at a low tidal volume by the V/P ratio at a high tidal volume. This ADI was then related to the effect of PEEP changes on respiratory compliance and alveolar to arterial oxygen tension difference (AaDO2). ADI was assumed to indicate alveolar collapse if less than 1 and overdistension if more than 1. An increased PEEP in neonates with alveolar collapse (ADI less than 1) decreased AaDO2 more (12 vs 10 mm Hg/cm PEEP, not significant) and decreased compliance less (3 vs 17%/cm PEEP; P < 0.05) than in those neonates with alveolar overdistension (ADI more than 1). Conversely, a decreased PEEP in neonates with alveolar overdistension increased compliance more (19 vs 5%; not significant) and increased AaDO2 less (7 vs 26 mm Hg; P < .01) than in those with alveolar collapse. AaDO2 and compliance changes after PEEP alterations were significantly correlated to the ADI before PEEP alterations (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "16052276", "8619207", "9841760", "9462386" ]

[ "Preoperative epoetin alfa in colorectal surgery: a randomized, controlled study.", "Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study.", "Recombinant human erythropoietin and hemoglobin concentration at operation and during the postoperative period: reduced need for blood transfusions in patients undergoing colorectal surgery--prospective double-blind placebo-controlled study.", "Randomized multicentre trial of the influence of recombinant human erythropoietin on intraoperative and postoperative transfusion need in anaemic patients undergoing right hemicolectomy for carcinoma." ]

[ "Colorectal cancer patients are often anemic before surgery, and this leads to an increased requirement for allogeneic blood transfusion. This may result in transfusion-induced immunosuppression, which in turn leads to increased morbidity and possibly an increased rate of tumor relapse. We investigated the possible benefits of perioperative epoetin alfa administration in anemic patients to correct hemoglobin levels and reduce transfusion needs.\n A total of 223 colorectal cancer patients with anemia scheduled for surgery were randomized to a group that received epoetin alfa 150 or 300 IU/kg/day subcutaneously for 12 days (day -10 to +1) or to a control group. All received iron (200 mg/day by mouth) for 10 days before surgery. Hemoglobin levels, hematocrit, and the number of blood units transfused were recorded.\n A total of 204 patients were eligible for analysis. Mean hemoglobin levels and hematocrit were significantly higher in the 300 IU/kg group than in the control group, both 1 day before surgery (hemoglobin, P = .008; hematocrit, P = .0005) and 1 day after surgery (hemoglobin, P = .011; hematocrit, P = .0008). Blood loss during and after surgery was similar in all groups. Patients who received epoetin alfa 300 IU/kg required significantly fewer perioperative transfusion units than control patients (.81 vs. 1.32; P = .016) and significantly fewer postoperative units (.87 vs. 1.33; P = .023). There were no significant differences in the number of units in the 150 IU/kg group.\n Preoperative epoetin alfa (300 IU/day) increases hemoglobin levels and hematocrit in colorectal surgery patients. These effects are associated with a reduced need for perioperative and postoperative transfusions.", "Blood transfusions are associated with higher postoperative morbidity and tumor recurrence rates in colorectal cancer surgery, To reduce the need for transfusions in patients with tumor-induced anemia who are not suitable for autologous blood donation, it was tested whether perisurgical erythropoietin application would be able to stimulate hematopoiesis adequately.\n In a double-blind randomized study 150 IU/kg body weight erythropoietin was given subcutaneously every 2 days beginning 10 days before operation and continuing until postoperative day 2. Twenty patients were randomized into the erythropoietin group with three observed dropouts and 10 patients into the placebo group.\n In the erythropoietin group two episodes of hypertension and one deep venous thrombosis were observed. Preoperative hemoglobin response in the erythropoietin group (p = 0.069) was paralleled by a highly significant reticulocyte increase (p = 0.0004). However, frequency of blood transfusion was not different between both study groups (erythropoietin, 1.82 +/- 0.80 units/ patient; placebo, 1.80 +/- 0.97 units/patient). If iron availability was analyzed, a strong correlation between ferritin blood levels and transferrin iron saturation with hemoglobin response was observed in regression analysis (p < 0.001).\n These results indicate that hematopoiesis in anemic patients with colorectal cancer can be stimulated by erythropoietin; however, clinical efficacy is to be expected only in selected patients with high iron availability, which calls for further studies combining erythropoietin and parenteral iron application.", "In a double-blind placebo-controlled study we investigated the effect of recombinant human erythropoietin (r-HuEPO), on the perioperative hemoglobin concentration and the use of blood transfusions in patients undergoing elective colorectal surgery with a preoperative hemoglobin level </=8.5 mmol/L. Altogether 100 were included, and 81 patients could be evaluated. A total of 38 patients received r-HuEPO in a dose of 300 IU/kg body weight on day 4 before surgery and 150 IU/kg daily for the following 7 days; 43 patients received placebo. In addition, all patients received daily doses of 200 mg iron orally for 4 days before surgery. There were no differences between the two groups with regard to sex, height, weight, serum electrolytes, and liver function tests at study entry. The preentry hemoglobin concentration was similar in the two groups, with a median value of 7.9 (range 5.3-8.5) mmol/L in the erythropoietin group and 7.6 (5.1-8.5) mmol/L in the placebo group. On the day of surgery the median hemoglobin concentration was 7.8 (5. 3-9.2) mmol/L in the erythropoietin group and 7.2 (4.6-8.5) mmol/L in the placebo group (p < 0.05). On postoperative days 3 and 7 the values were 7.2 (5.3-8.2) and 7.5 (5.4-9.4) mmol/L, respectively, in the erythropoietin group compared to 6.7 (5.2-7.8) and 6.9 (5.1-8.6) mmol/L in the placebo group (p < 0.01). At discharge the hemoglobin concentration was 7.8 (5.9-8.8) mmol/L in the erythropoietin group and 7.2 (5.4-8.6) mmol/L in the placebo group (p < 0.002). The blood loss during operation was similar in the two groups. In the erythropoietin group the median value was 280 ml (range 25-2000 ml), with the lower and upper quartiles 150 and 500 ml, respectively. In the placebo group the blood loss was median 300 ml (range 50-1800 ml), with the lower and upper quartiles 200 and 750 ml, respectively. The number of blood transfusions given was significantly lower in the erythropoietin group, with a mean of 0.3 (range 0-6) units compared to 1.6 (0-9) units in the control group (p < 0.05). In conclusion, the hemoglobin concentration at the time of surgery and during the week following surgery was significantly higher in the group of patients receiving r-HuEPO perioperatively compared to the placebo group together with a significant lower use of blood transfusions in the r-HuEPO group. However, the clinical implications of these findings has yet to be proven.", "The possible immunosuppressive effect of blood transfusion and its influence on survival after surgery for cancer makes it worthwhile to seek methods to avoid transfusion wherever possible. Patients with right-sided colonic cancer are frequently anaemic. Such patients were entered into a study that employed erythropoietin to avoid homologous transfusion.\n In a prospectively randomized double-blind placebo-controlled multicentre trial, patients with moderate anaemia (haemoglobin concentration greater than 8.5 g/dl and less than or equal to 13.5 g/dl) presenting with right-sided colonic cancer and scheduled for hemicolectomy were treated with recombinant human erythropoietin (epoetin beta) 20,000 units/day subcutaneously or placebo for at least 10 days over the operative period.\n Perioperative treatment with epoetin beta was well tolerated and there were no significant differences in morbidity and mortality. Following hemicolectomy, median cumulative blood loss in the two groups was similar (epoetin beta 440 ml versus placebo 345 ml). Sixteen (33 per cent) of 48 patients treated with epoetin beta and 15 (28 per cent) of 54 in the placebo group received perioperative blood transfusions (P not significant). The increase in reticulocyte count between baseline and the last preoperative value was more pronounced in the epoetin beta group than in those receiving placebo (P = 0.036).\n Despite the perioperative administration of 20,000 units erythropoietin per day for at least 10 days, it was not possible to reduce the intraoperative and postoperative transfusion need. None the less, a positive change in the haematological variables of treated patients was clearly discernible. The negative result may be due to the short treatment interval and to iron deficiency, which was present in the majority of patients. The general change of attitude towards allogeneic blood transfusion is demonstrated by the overall low frequency of blood transfusion in this study." ]

[ "8705223", "2203517", "8518017", "9563140", "2285605", "8367920", "1834864", "3309973", "2681086", "3116551", "2151276", "8776812", "2144207", "2973169", "9186345", "2503724", "9761805", "8252509" ]

[ "Bilateral orchidectomy and flutamide versus orchidectomy alone in newly diagnosed patients with metastatic carcinoma of the prostate--an Australian multicentre trial.", "A controlled trial of castration with and without nilutamide in metastatic prostatic carcinoma.", "Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. The Italian Prostatic Cancer Project (PONCAP) Study Group.", "Complete androgen blockade versus chemical castration in advanced prostatic cancer: analysis of an Italian multicentre study. Italian Leuprorelin Group.", "A randomized double-blind study evaluating Anandron associated with orchiectomy in stage D prostate cancer.", "Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center.", "A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. The International Prostate Cancer Study Group.", "Anandron (RU 23908) associated to surgical castration in previously untreated stage D prostate cancer: a multicenter comparative study of two doses of the drug and of a placebo.", "[Therapy of metastatic prostatic cancer by orchiectomy plus Anandron versus orchiectomy plus placebo. Initial results of a randomized multicenter study].", "Double-blind study of Anandron versus placebo in stage D2 prostate cancer patients receiving buserelin. Results on 49 cases from a multicentre study.", "Total androgen blockade with Zoladex plus flutamide vs. Zoladex alone in advanced prostatic carcinoma: interim report of a multicenter, double-blind, placebo-controlled study.", "Combination treatment versus LHRH alone in advanced prostatic cancer.", "A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate.", "Evaluation of total versus partial androgen blockade in the treatment of advanced prostatic cancer.", "Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. International Anandron Study Group.", "A controlled trial of leuprolide with and without flutamide in prostatic carcinoma.", "Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.", "Combination treatment in M1 prostate cancer." ]

[ "To investigate the hypothesis that maximal androgen blockade improves the outcome of patients with metastatic prostate cancer.\n A total of 222 previously untreated patients with metastatic prostatic cancer were entered into a randomized, double-blind, placebo-controlled trial of bilateral orchidectomy with or without androgen blockade (112 receiving flutamide and 110 a placebo) which commenced in 1985 in four Australian centres. The characteristics of the patients, e.g. age, performance status, the presence of bone pain, duration of disease and the use of prior radiation, were well balanced between the groups. Patients commenced the protocol therapy with flutamide or placebo within the 7 days preceding surgery and continued this medication for a minimum of 2 years, unless there was unequivocal evidence of tumour progression.\n Apart from a difference in grade 3 or 4 gastrointestinal toxicities between the flutamide and placebo arms (13% and 3%, respectively), serious or life-threatening toxicities were uncommon and equally balanced. The assessment of response in six patients (three in each arm) was inevaluable. The objective response rates were 45% and 56% in the flutamide and placebo arms, respectively. There was no difference in survival between the treatments.\n This study was not sufficiently powerful to detect small differences in outcome (although the trend in survival favoured the placebo arm) but nevertheless failed to show any benefit for maximal androgen blockade over orchidectomy in this group of patients.", "A randomized double-blind trial in patients with disseminated, previously untreated prostate cancer (Stage D2) was conducted in eight Canadian centers. All 203 patients enrolled in this study underwent bilateral orchiectomy and were randomized to receive either the nonsteroidal anti-androgen nilutamide or a placebo. Patient responses were graded according to the criteria of the National Prostatic Cancer Project (NPCP). Patients treated with nilutamide had a significantly greater number of positive objective responses (partial and complete regression) than did the patients treated with castration alone (46% versus 20%, P = 0.001). Progression-free survival was improved initially in the nilutamide group, but the median time to progression was 12 months for both groups. Despite an increase in the median length of survival from 18.9 to 24.3 months with the nilutamide, the survival time was not significantly longer in the nilutamide group (log = rank test, P = 0.048). Although minor side effects were frequent, adverse effects related to the medication and leading to discontinuation of treatment were observed in 9% of cases. These results suggest some benefit of the combined treatment (orchiectomy + nilutamide) over orchiectomy alone in the treatment of metastatic prostatic carcinoma.", "From March 1987 to December 1990, 373 patients with stage C and D prostate cancer were randomized to receive either goserelin acetate alone or goserelin acetate plus flutamide. At a median follow-up time of 24 months, there was no significant difference in the response rate, progression-free and overall survival between the two treatment groups. In particular, median time to progression was 18 months in the goserelin arm and 24 months in the combined treatment arm (P = 0.09). However, median time to progression in stage D patients was 12 months in both treatment groups. Median time to death was 32 and 34 months, respectively. The combination regimen produced a more rapid normalisation of prostatic acid phosphatase levels and a prompt relief of bone pain. However, significantly more patients in the combination arm experienced treatment-related side-effects such as diarrhoea and increases in transaminase levels. The concurrent use of goserelin acetate and flutamide does not seem to significantly improve the results that can be achieved with goserelin acetate alone.", "In spite of a great amount of data, the hormonal treatment of advanced prostatic carcinoma (CaP) still remains controversial. As a relevant amount of dihydrotestosterone is present within the prostate tissue after castration, complete androgen blockade (CAB), with inhibition of the activity of both testicular and adrenal androgens, has been advocated as up-front treatment of advanced CaP. However, many controlled studies have failed to demonstrate a benefit for CAB in comparison with simple surgical or chemical castration. The present study was performed to bring additional data for a worldwide meta-analysis of all phase III trials comparing castration and CAB.\n This is a centrally controlled phase III study in which chemical castration with leuprorelin acetate depot was compared with leuprorelin plus flutamide in stage C and D CaP. Two hundred and forty-one eligible and evaluable patients with histologically proven CaP were recruited for the study (120 treated with castration and 121 with CAB). The diagnostic and staging workup consisted of blood chemistry, general condition assessment, prostate-specific antigen (PSA), abdominal sonography and computed tomography scan, and whole-body isotopic bone scan. End points of the study were survival, time to treatment failure, and time to progression. The patients were followed every 6 months with PSA and sonography.\n At a cut-off analysis performed in December 1996, when the mean follow-up period was 43.7 +/- (SD) 24.1 months, no statistical differences in terms of time to treatment failure, time to progression, and death rate could be detected. Also considering the common risk factors, such as basal PSA, haemoglobin, alkaline phosphatase, and Gleason score, the outcome did not show any clear advantage for CAB.\n This study appears to confirm that the advantages of first-line CAB in CaP are at best marginal. The final analysis will be performed when the follow-up period has reached 5-years, but it seems unlikely that the present results will change.", "A randomized double-blind study with a 3-yr follow-up comparing the two arms \"orchiectomy + Anandron (300 mg)\" vs \"orchiectomy + placebo\" in 125 patients with stage D prostate cancer has confirmed the beneficial effects of the combined Anandron therapy on subjective parameters and on the best objective response (NPCP criteria), although these effects were not statistically significant, but failed to detect any improvement in time-to-disease progression or survival. Comparison with the results of other trials emphasizes the urgent need to establish suitable prognostic factors by further clinical research before evaluating the benefits of individual drugs.", "Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.", "A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.", "nan", "In the course of a randomized double blind trial conducted by 7 Swiss urological centres, 51 patients with advanced, not pretreated carcinoma of the prostate were included. Following orchiectomy the patients were either administered 300 mg Anandron daily (Roussel RU 23908) or Placebo. Twelve months later the Anandron-group shows a slightly better objective response whereas there is no difference in survival rates. The adverse effects of Anandron-treatment are described.", "nan", "A double-blind, placebo-controlled, randomized, multicenter study was undertaken to investigate the effects of Zoladex plus flutamide vs. Zoladex plus placebo in patients with advanced prostatic cancer. Interim analysis has revealed no differences between the 2 groups in objective or subjective responses at 6 months' follow-up or in overall survival and time to disease progression at 15 months' follow-up.", "Androgen deprivation based on hormone manipulation is the treatment of choice in advanced prostatic cancer. The unequivocal role of adrenal androgens in the growth of prostatic cancer after medical or surgical castration requires a new logical approach (complete androgen blockade) in the treatment of advanced prostate cancer. One hundred and fifty patients with biopsy-proven advanced prostatic cancer were randomized into two groups. One group (74 patients) received leuprolide + flutamide (complete androgen blockade); the second group (76 patients) received only leuprolide and, during the first 3 weeks of treatment, cyproterone acetate (150 mg/day) to prevent flare-up phenomena. The aim of the study was to evaluate the differences between the two groups on overall survival and time to progression (log-rank test). One hundred and twenty-five patients were evaluable, 62 in the leuprolide-only group and 63 in the leuprolide + flutamide group. Median duration of follow-up was 102 weeks. No statistical difference between the two groups was observed in overall survival, in time to disease progression, and in time to treatment failure. In the combination (leuprolide + flutamide) treatment group, a positive trend for overall survival and in time to progression was observed in a subgroup of patients with good performance status and no bone metastases. We observed mild gastrointestinal toxicity (diarrhea, nausea) in the group treated with leuprolide + flutamide. The aim of this study was to compare the effectiveness of total androgen withdrawal with medical testicular suppression in advanced prostatic cancer. No significant statistical difference was observed between the two groups in overall survival and in time to progression, but probably too few patients were enrolled in each treatment arm to give a statistical interpretation of our results. We conclude that there is a positive trend in the combination treatment arm in patients with good prognostic factors.", "In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate.", "In order to evaluate the proposed benefit of complete androgen blockade in the treatment of patients with advanced prostatic cancer, we initiated a multicenter prospective and randomized study. At the time of this report 99 patients with newly diagnosed, previously untreated prostatic cancer were randomly distributed to one of the following treatments: group I, orchiectomy plus antiandrogen Flutamide; group II, depot LH-RH analog Zoladex plus Flutamide; group III, orchiectomy alone, and group IV, Zoladex alone. Our preliminary data fail to demonstrate a superiority of total androgen blockade over partial androgen blockade in the treatment of patients with advanced cancer of the prostate.", "We studied the long-term efficacy and tolerability of nilutamide, a nonsteroidal antiandrogen, combined with orchiectomy in patients with advanced prostate cancer.\n A large double-blind trial was done on 457 patients randomized to receive nilutamide or placebo after orchiectomy.\n At 8.5 years of followup significant benefits were found for progression and survival in favor of patients receiving nilutamide and orchiectomy. In addition, normalized prostate specific antigen levels at 3 months from the start of therapy were predictive of good long-term outcome. Moreover, combined androgen blockade with nilutamide increased the chance of patients having normal prostate specific antigen levels at 3 months. Nilutamide was well tolerated in the long term with no increase in the incidence of drug specific adverse events.\n With long-term followup of patients with advanced prostate cancer, the combination of nilutamide and orchiectomy has significant benefits in interval to progression and improved survival compared to orchiectomy and placebo.", "To test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer, we conducted a randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2). All 603 men received leuprolide, an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins, in combination with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. As compared with the 300 patients receiving leuprolide and placebo, the 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival (16.5 vs. 13.9 months; P = 0.039) and an increase in the median length of survival (35.6 vs. 28.3 months; P = 0.035). The differences between the treatments were particularly evident for men with minimal disease and good performance status; however, further studies should be conducted in this subgroup. Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade, when leuprolide alone often produces a painful flare in the disease. We conclude that in patients with advanced prostate cancer, treatment with leuprolide and flutamide is superior to treatment with leuprolide alone.", "Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy.\n We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status.\n Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall, the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease.\n The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.", "The treatment of advanced prostate cancer is based on hormone manipulation to eliminate the trophic effect of testosterone on sensitive androgen tissue of the tumor. In this study, we evaluated the efficacy of the partial androgen blockage versus the complete androgen blockage. One hundred, twenty-two patients were entered in this study and randomly were treated with buserelin alone or with buserelin and flutamide. The group that received buserelin was given cyproterone acetate (200 mg/day) during first 3 weeks of treatment to avoid \"flare-up\". During the follow-up (range 0-244 +/- 1 weeks), we evaluated 59 patients (61.4%) that had positive response and 37 patients (38.6%) that showed progressive disease: There were no statistically significant differences between the two treatment groups, not even in the evaluation of median time to response and of median time to treatment failure. In conclusion, the results emphasize that total androgenic blockage is as effective as a luteinizing hormone-releasing hormone analog used alone." ]

[ "10328861", "15493096", "7844481" ]

[ "Fast and slow namers: benefits of segmentation and whole word training.", "Remediating the core deficits of developmental reading disability: a double-deficit perspective.", "Early identification and remediation of phonological-processing deficits in first-grade children at risk for reading disabilities." ]

[ "Poor readers in Grade 2 (mean age 7 years 7 months) were categorized into fast and slow namer groups based on their performance on a Rapid Automatized Naming (RAN) task. The fast and slow groups were then trained to read words using 3 different training regimes: one that taught onset/rime segmentation, one that taught phonemic segmentation, and one that used whole word repetition. The main results were that the slow namers acquired the words more slowly across experiences than the fast namers, irrespective of training condition, but they were particularly disadvantaged when trained with word-level units. Unlike beginning nonreaders, poor Grade 2 readers showed poorer retention following onset/rime training compared with phoneme or word level training, even when final level of learning was controlled. Further, they showed the best generalization to reading new words and nonwords following phoneme training and the worst following whole word training, even when final level of acquisition was controlled. The data are related to the P. G. Bowers and M. Wolf (1993, Reading and Writing, 5, 69-85) double-deficit hypothesis and to the specific deficits associated with early reading failure.\n Copyright 1999 Academic Press.", "The double-deficit hypothesis (Wolf, 1997; Wolf & Bowers, 1999, this issue) contends that deficits in phonological awareness and deficits in visual naming speed represent two independent causal impediments to reading acquisition for children with developmental reading disabilities (RD). One hundred and sixty-six children with severe RD from 7 to 13 years of age were classified into three deficit subgroups according to a double-deficit framework. A total of 140 children with RD, 84% of the sample, were classified; 54% demonstrated a double deficit (DD), 22% a phonological deficit only (PHON), and 24% a visual-naming speed deficit only (VNS). Diagnostic test profiles highlighted the joint contributions of the two core deficits in depressing written language acquisition. The children in the DD group were more globally impaired than those in the other subgroups, and the VNS group children were the highest achieving and most selectively impaired readers. Following 35 hours of word identification training, sizable gains and significant generalization of training effects were achieved by all subgroups. A metacognitive phonics program resulted in greater generalized effects across the domain of real English words, and a phonological training program produced superior outcomes within the phonological processing domain. The greatest non-word reading gains were achieved by children with only phonological deficits.", "The present study assessed 486 first-quarter first graders on their reading and phonological-processing skills and intelligence. Based on this assessment, and using the classification data from Hurford et al.'s (1993) study, 99 children were identified as being at risk for reading difficulties: 53 children at risk for reading disabilities (RD) and 46 children at risk for becoming \"garden-variety\" poor readers (GV). Half of the RD and GV groups received the phonological-processing intervention. Posttraining assessment indicated that the training procedure not only was effective in increasing the phonological-processing skills of the trained participants, but also increased their reading ability. Both of the RD and GV trained groups benefited from the training. Analyses also indicated that the initial screening device was somewhat less accurate in the present study in identifying at-risk children than in our previous studies (85% vs. approximately 98%, respectively). The results of the present study indicate that it is possible to identify children at risk for reading difficulties and to significantly improve their phonological-processing and reading abilities." ]

[ "3456849", "9239953", "6948831", "12532056", "14718877", "11455374", "9699448", "10926433", "280551", "9800441", "11029829", "9472145", "2650531", "11455377" ]

[ "Action of fluoride on initiation of early enamel caries in vivo. A microradiographical investigation.", "White spot reduction when using glass ionomer cement for bonding in orthodontics: a longitudinal and comparative study.", "MFP versus stannous fluoride mouthrinses for prevention of decalcification in orthodontic patients.", "In vivo inhibition of demineralization around orthodontic brackets.", "In vivo effect of a resin-modified glass ionomer cement on enamel demineralization around orthodontic brackets.", "Effects of combined application of antimicrobial and fluoride varnishes in orthodontic patients.", "Fluoride release and cariostatic ability of a compomer and a resin-modified glass ionomer cement used for orthodontic bonding.", "A comparative clinical trial of a compomer and a resin adhesive for orthodontic bonding.", "Control of decalcification by use of fluoride mouthrinse.", "Cariostatic effect of a light-cured, resin-reinforced glass-ionomer for bonding orthodontic brackets in vivo. A combined study using microradiography and confocal laser scanning microscopy.", "Fluoride-releasing elastomerics--a prospective controlled clinical trial.", "Cariostatic effect of glass ionomer retained orthodontic appliances. An in vivo study.", "An evaluation of a fluoride-releasing, visible light-activated bonding system for orthodontic bracket placement.", "Modified composite or conventional glass ionomer for band cementation? A comparative clinical trial." ]

[ "nan", "The aim of this clinical study was to test the benefit from using glass ionomer cement (GIC) instead of a conventional diacrylate in bracket bonding for the prevention of white spot formation. Before treatment 7.2 per cent of all examined surfaces (n = 222) were classified as having white spots. No additional fluoride treatment other than fluoride toothpaste was prescribed. At debonding 8-39 months later, white spots were found in 24 per cent of the surfaces bonded with the cement, significantly lower than the 40.5 per cent bonded with the diacrylate (P < 0.01). At recall 12 months after debonding (examined surfaces n = 214) the frequency of surfaces with white spots was reduced to 22 and 24 per cent respectively. Re-examination after a further 12 months (n = 160) showed that white spot surfaces were less frequent with the cement (16 per cent compared with the diacrylate 29 per cent), but still significantly more frequent in both groups than before treatment. With longer treatment time (17 months) teeth bonded with diacrylate were more frequently affected with white spots (P < 0.05). Neither sex nor age affected the results. It is concluded that the use of a GIC for orthodontic bonding will result in a significant reduction in the number of white spot surfaces at debonding compared with the use of conventional diacrylate. Although markedly reduced in both groups, the number of affected surfaces was still higher 2 years after debonding than before treatment.", "Twenty-two orthodontic patients in the eleven to fifteen-year age-group participated in a one-year fluoride rinsing program. A 0.1 percent SnF2 solution was compared to a MFP solution containing an equivalent amount of fluoride. A laboratory study evaluated the enamel solubility reducing capacities of the two solutions. Enamel solubility reduction by a two-minute treatment with 0.1 percent SnF2 was 77.8 percent; that for MFP solution was only 13.1 percent. Rinsing daily with SnF2 prevented decalcification completely in twelve patients; two of ten patients rinsing with MFP developed new decalcification during orthodontic treatment. Thus, SnF2 was more effective than MFP in both the laboratory and clinical phases of the study. These results support the requirement for frequent applications, if patients are at advanced risk, and suggest that the method of treatment is at least as important as the choice of specific fluoride.", "Demineralization around orthodontic appliances is a problem. Suboptimal oral hygiene, long intervals between appointments, and potentially poor patient cooperation with using fluoride dentifrices and mouth rinses necessitate a compliance-free means of preventing tooth decay. The hypothesis of this study was that fluoride released by glass ionomer cement inhibits the formation of carious lesions around orthodontic brackets in vivo. Brackets were bonded on 2 first premolars in 21 randomized, consecutively selected patients 11 to 18 years old. Eleven test-group subjects were bonded with fluoride-releasing glass ionomer cement, and 10 control subjects were bonded with composite resin (no fluoride). The teeth were extracted after 4 weeks, sectioned, and evaluated quantitatively by cross-sectional microhardness testing. Fluoride levels in patient saliva were measured by the Taves diffusion method in samples taken at days 0 (baseline), 1, 2, 3, 7, 14, 21, and 28 to determine whether fluoride from the glass ionomer cement influenced the overall intraoral fluoride levels. The results demonstrated significantly more demineralization around the brackets of the control patients (P <.01, Wilcoxon signed rank test). For whole-mouth salivary fluoride levels, no significant overall difference between the groups (P >.05) and no noticeable trend within groups (P >.05) were found. These results indicate that using fluoride-releasing glass ionomer cement for bonding orthodontic brackets successfully inhibited caries in vivo. This cariostatic effect was localized to the area around the brackets and was statistically significant after 4 weeks.", "Because the risk of dental caries increases with the use of orthodontic appliances and its control cannot depend only on the patient's self-care, this study evaluated the effect of a glass ionomer cement on reducing enamel demineralization around orthodontic brackets. Fourteen orthodontic patients were randomly divided into 2 groups of 7; they received 23 brackets fitted to their premolars, bonded with either Concise (3M Dental Products, St Paul, Minn), a composite resin (control group), or Fuji Ortho LC (GC America, Chicago, Ill), a resin-modified glass ionomer cement (experimental group). The volunteers lived in a city that has fluoridated water, but they did not use fluoridated dentifrices during the study. After 30 days, the teeth were extracted and longitudinally sectioned; in the enamel around the brackets, demineralization was assessed by cross-sectional microhardness. The determinations were made at the bracket edge cementing limits, and at occlusal and cervical points 100 and 200 microm away from them. In all of these positions, indentations were made at depths from 10 to 90 microm from enamel surface. Analysis of variance showed statistically significant effects for position, material, depth, and their interactions (P<.05). The Tukey test showed that the glass ionomer cement was statistically more efficient than the control, reducing enamel demineralization in all analyses (P<.05). The use of glass ionomer cement for bonding can be encouraged because it decreases the development of caries around orthodontic brackets.", "A randomized prospective clinical study, with 220 patients scheduled for fixed orthodontic therapy, was conducted to test the hypothesis that application of an antimicrobial varnish in combination with a fluoride varnish (group 1) is significantly more efficient in reducing white spot lesions on the labial surfaces than application of the fluoride varnish alone (group 2). The effects of the antimicrobial varnish on the occurrence of gingivitis and plaque formation were also studied. A third aim was to investigate whether white spot lesion development could be predicted early during treatment. The antimicrobial varnish significantly reduced the number of mutans streptococci in plaque during the first 48 weeks of treatment. This effect did not result in significantly less development of white spot lesions on the labial surfaces compared with the group receiving only the fluoride varnish application. There was however a clear trend that the combination of the antimicrobial and fluoride varnishes more effectively reduced the increments of new lesions on the maxillary incisors. It was speculated that this could be due partly to an inhibiting effect of the antimicrobial varnish in an area with low oral clearance (with low pH and loss of fluoride) and partly to an inhibiting effect of the varnish on mutans streptococci. No significant differences between the groups with respect to gingivitis and plaque were found. Lesion development was difficult to predict early after bonding, despite a number of caries-relevant parameters of orthodontic importance. The best predictors for white spot lesions at debonding were visible plaque and mutans streptococci (eg, the level of oral hygiene and thus the cariogenic challenge) around the appliance shortly after bonding.", "The aims of this study were to compare the local and systemic uptake of fluoride released from a compomer material (Dyract Ortho) and a resin-modified glass ionomer cement (Vitremer) with that of a conventional resin adhesive (Right-On) and to compare the cariostatic ability of each of the test materials with that of the resin control.\n Twenty six patients were randomly allocated to have a bracket bonded to a premolar on one side of the arch with one of the test materials and on the opposite side with the control material. Premolars destined for extraction as part of an orthodontic treatment plan were selected for bonding. A non-fluoride toothpaste was used by all participants for 4 weeks prior to bracket bonding and throughout the 4 week trial period. Fluoride release was measured in saliva, plaque and urine samples taken pre-bonding and 4 weeks post-bonding. Enamel demineralisation was assessed by scoring the buccal surface of each extracted tooth using a caries index.\n Neither Vitremer nor Dyract Ortho altered salivary or urinary fluoride concentration significantly 4 weeks post-bonding but plaque fluoride concentration increased significantly around premolars bonded with Vitremer. The test materials as a combined group were associated with significantly less demineralisation than the control material but there was no significant difference in cariostatic ability detected between either Dyract Ortho or Vitremer when each group was compared separately with the control.\n Fluoride released from Dyract Ortho or Vitremer is likely to exert a local and not a systemic effect. In a 4-week clinical study, the cariostatic ability of the fluoride-releasing cements, as a combined group, was superior to that of the non-fluoride releasing control but there was no significant difference in cariostatic ability between the two test materials when each test group was compared separately with the control.", "The study aimed to compare the survival time and cariostatic potential of a compomer to that of a resin adhesive when used to bond stainless steel orthodontic brackets to labial segment teeth only. The effect of the patients' sex, age at the start of treatment and presenting malocclusion on bracket survival time was assessed also. Forty-five consecutive patients who attended for fixed appliance therapy were randomly selected. Four hundred twenty-six brackets were bonded (213 with compomer and 213 with resin adhesive) with a split mouth design; the right or left side allocation of compomer in either arch was alternated. Color transparencies of the maxillary incisors, mandibular incisors, or both, and transparencies of the canines, were taken before treatment. At the debond stage, the transparencies were projected (20x) and assessed by an experienced examiner, who used a caries index. The survival time distributions for brackets bonded with each bonding agent were not significantly different (P = .74, paired Prentice-Wilcoxon test; P = .75, Akritas test), with bracket failure rates of 17% and 20% recorded for compomer and resin adhesive, respectively. Neither the patients' sex (P = .85) nor malocclusion (P = .26) appear to affect significantly bracket survival, but patient age was identified as a useful prognostic indicator of bracket survival (P < .001). On average, there was more decalcification related to brackets bonded with resin adhesive than with compomer (P = .0075). Survival time distributions of brackets bonded with compomer or resin adhesive appear comparable, but decalcification was reduced significantly by bonding with compomer.", "nan", "The aim of this study was to evaluate in vivo the cariostatic potential of the resin-reinforced glass-ionomer (Vitremer core build-up restorative; 3M Dental Product Division) when used as a bonding agent for orthodontic brackets. The mineral distribution and topography of the enamel surface adjacent to the bracket base was determined by quantitative microradiography (TMR) and confocal laser scanning microscopy (CLSM). The study was designed in split-mouth technique using 9 pairs of premolars to be extracted for orthodontic reasons. One tooth of each pair was bonded with the resin-reinforced glass-ionomer, and the control contralateral premolar with the non-fluoridated composite (Concise, 3M Dental Products Division). After 4 weeks all teeth were extracted and stored until analysis. The lesion depths and mineral loss values in enamel adjacent to brackets bonded with Vitremer were significantly lower than in teeth bonded with the composite, indicating that the resin-reinforced glass-ionomers significantly reduced caries lesion development in vivo. CLSM images show a severe cariogenic challenge around orthodontic brackets and support TMR measurements.", "A prospective controlled clinical trial was undertaken to evaluate the effectiveness of stannous fluoride-releasing elastomeric modules (Fluor-I-Ties) and chain (Fluor-I-Chain) in the prevention of enamel decalcification during fixed appliance therapy. Forty-nine patients (782 teeth) were included in the experimental group, where the fluoride-releasing elastomerics were used. Forty-five patients (740 teeth) who received non fluoride-releasing elastomerics formed the control group. All patients had their elastomerics replaced at each visit. Enamel decalcification incidence and distribution were recorded using an index by direct clinical observation. In the control group enamel decalcification occurred in 73 per cent of patients and in 26 per cent of all teeth. In the experimental group the corresponding incidence was 63 and 16 per cent, respectively. The overall reduction in score per tooth produced by the fluoride-releasing elastomerics was 49 per cent, a highly significant difference (P < 0.001). A significant difference was seen in all but the occlusal enamel zones. The majority (over 50 per cent) of lesions occurred gingivally. The teeth most severely affected were the maxillary lateral incisors and mandibular second premolars. There was no difference in treatment duration between groups.", "The cariostatic effect of a fluoride releasing bonding agent was investigated and compared with a conventional composite based material in connection with bonding of orthodontic brackets in 22 homologous pairs of premolars. All subjects had malocclusions requiring orthodontic treatment with fixed appliances and extraction of at least two premolars. 6-13 weeks prior to extraction, orthodontic brackets were bonded to the labial surfaces of the extraction teeth with either a glass ionomer cement or a bis-GMA resin. Initially, the children were instructed in tooth brushing and the regular use of fluoride. After extraction, the bonded teeth were stained and evaluated in a stereo-microscope regarding the incidence and extension of initial enamel demineralisation. The zone of intact enamel adjacent to the bracket base and bonding material was measured in a stereo-microscope at four predetermined locations with the aid of an electronic ruler and scored according to four categories. The incidence of enamel demineralisation adjacent to glass ionomer bonded and composite bonded brackets was 68% and 77% respectively. In 12 pairs of premolars however, the demineralisation appeared to a lesser extent on the enamel around the brackets was generally wider when glass ionomer cement was used compared to the composite resin. These differences were statistically significant (p < 0.05) mesially and distally, but non-significant cervically and incisally. The results indicate that bonding with glass ionomer cement may have a local cariostatic effect in children requiring fixed orthodontic appliances.", "In spite of improved preventive measures, decalcification around bonded orthodontic appliances continues to be a problem for the clinician. Various fluoride-containing mediums have been proposed as aiding in the elimination of this problem; however, almost all are dependent on patient cooperation for their success. An ideal preventive system would be one that would operate independently of patient cooperation. The purpose of the present study was to compare a visible light-activated, fluoride-releasing bonding system with a visible light-activated conventional bonding system relative to bracket retention and prevalence of decalcification. Twenty-two patients were entered into the study, representing 206 experimental brackets and 206 control brackets. The average treatment period was 25 months. No significant differences in bracket retention rates were found between the two systems. Significantly, 26 teeth in the control group demonstrated decalcification (12.6%), whereas none of the teeth in the experimental group did. The results of this study suggest that a visible light-activated, fluoride-releasing bonding system is capable of adequately retaining brackets while aiding in the prevention of decalcification around bonded appliances.", "The time to first failure, the position of band failure at deband, and the change in enamel white spot lesions of teeth bonded with a modified composite or a conventional glass ionomer were compared in a randomized half-mouth trial over the full course of orthodontic treatment. One hundred forty band pairs were cemented in 98 subjects. Overall band failure rates of 5% and 2.8% were recorded for the modified composite and the conventional glass ionomer, respectively, with no significant difference found between their times to first band failure. At the end-of-treatment deband, the position of band failure was predominantly at the enamel-cement interface for the modified composite and at the band-cement interface for the conventional glass ionomer (P <.001). A comparison of changes in mean enamel white spot lesion scores during treatment did not reveal significant differences between the cement groups (P =.16)." ]