Datasets:

allenai

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mslr2022

like 8

[ "3300672", "16105793", "2646187", "1584259", "17329511", "7096941", "3109575", "4898652", "9359441", "15925045", "1350540", "11767219", "3472467", "48000", "7710467", "16142136", "2698591" ]

[ "A randomized trial of induction at 42 weeks gestation versus expectant management for postdates pregnancies.", "Comparison of elective induction of labor with favorable Bishop scores versus expectant management: a randomized clinical trial.", "Is induction of labor indicated in prolonged pregnancy? Results of a prospective randomised trial.", "Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. A randomized controlled trial. The Canadian Multicenter Post-term Pregnancy Trial Group.", "Induction of labor or serial antenatal fetal monitoring in postterm pregnancy: a randomized controlled trial.", "[Comparison of 2 obstetrical attitudes vis-à-vis inducing labor at term. Randomized study].", "Randomised comparison of early versus late induction of labour in post-term pregnancy.", "A controlled trial of surgical induction of labour and amnioscopy in the management of prolonged pregnancy.", "Pregnancy outcome beyond 41 weeks gestation.", "Induction of labor with three different techniques at 41 weeks of gestation or spontaneous follow-up until 42 weeks in women with definitely unfavorable cervical scores.", "Prolonged pregnancy: the management dilemma.", "Management of prolonged pregnancy: a randomized trial of induction of labour and antepartum foetal monitoring.", "Management of prolonged pregnancy: induction of labor versus antepartum fetal testing.", "Elective induction of labour. A randomised prospective trial.", "A clinical trial of induction of labor versus expectant management in postterm pregnancy. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.", "[Management of pregnancies beyond forty-one week's gestation with an unfavorable cervix].", "Comparison of induced versus non-induced labor in post-term pregnancy. A randomized prospective study." ]

[ "A randomized prospective clinical trial of induction of labor at 42 completed weeks gestation versus expectant management in postdates pregnancies was performed. The primary screening test was the 24-hr urinary estriol creatinine ratio. The cesarean section rate was high in both groups and did not differ statistically. Intervention by delivery at 42 weeks decreased the development of small for gestational age infants, but costs slightly more. Twenty-four-hour urinary estriol creatinine ratio determinations predicted fetal distress in labor, but could not predict postmaturity syndrome or infants who were small for gestational age. As expectant management did not differ from induction of labor at 42 weeks from the standpoint of maternal outcome, and as the cost difference was small, induction of labor at 42 weeks may be the preferred management as it improves infant outcome.", "To determine if elective induction (IND) increases the risk of cesarean delivery compared to expectant management (EM).\n A randomized clinical trial involving women 39 weeks' gestation, according to strict dating criteria, with a Bishop score of 5 or more in nulliparous patients and 4 or more in multiparous patients. The control group was expectantly managed and delivered for obstetric indications, but not later than 42 weeks' gestation. The study had 80% power to detect a three-fold increase in cesarean delivery.\n One-hundred-and-sixteen patients (45 nulliparous) were randomized to IND and 110 (58 nulliparous) to EM. Demographic characteristics were no different between the groups. The cesarean delivery rate in the IND group was 6.9% (8/116) compared to 7.3% (8/110) in the EM group (p = NS). Rates of cesarean delivery for nulliparous patients randomized to IND compared to EM were also not significantly different: 13.3% (6/45) versus 10.3% (6/58) respectively (p = NS). Neonates delivered of IND patients weighed less than those of the EM group (3459 +/- 347 versus 3604 +/- 438, p = 0.006).\n In women with favorable Bishop scores, elective induction of labor resulted in no increase in cesarean delivery compared to expectant management.", "In 345 women with a favorable cervical score at due date, labor was either induced by means of intravaginal application of tablets containing 3 mg of prostaglandin E2 or spontaneous onset of labor was awaited until the 42nd week of pregnancy. Eighty percent of the nulliparae and 96.3% of the multiparae of the induction group gave birth within 24 h of the administration of the first tablet. All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labor was awaited. The rate of operative deliveries was lower in the induction group. With the exception of 1 fetal death 3 days after due date, fetal outcome was excellent in both groups. Elective induction was at least equivalent to awaiting the onset of spontaneous labor and was not associated with higher complication rates due to the method of induction.", "The rates of perinatal mortality and neonatal morbidity are higher for post-term pregnancies than for term pregnancies. It is not known, however, whether the induction of labor results in better outcomes than does serial fetal monitoring while awaiting spontaneous labor.\n We studied 3407 women with uncomplicated pregnancies of 41 or more weeks' duration. The women were randomly assigned to undergo induction of labor or to have serial antenatal monitoring and spontaneous labor unless there was evidence of fetal or maternal compromise, in which case labor was induced or cesarean section was performed. In the induction group, labor was induced by the intracervical application of prostaglandin E2. Serial antenatal monitoring consisted of counts of fetal kicks, nonstress tests, and assessments of amniotic-fluid volume. The outcomes we measured were the rates of perinatal mortality, neonatal morbidity, and delivery by cesarean section.\n Among the 1701 women in the induction group, 360 (21.2 percent) underwent cesarean section, as compared with 418 (24.5 percent) of the 1706 women in the monitoring group (P = 0.03). This difference resulted from a lower rate of cesarean section performed because of fetal distress among the women in the induction group (5.7 percent vs. 8.3 percent, P = 0.003). When two infants with lethal congenital anomalies were excluded, there were no perinatal deaths in the induction group and two stillbirths in the monitoring group (P not significant). The frequency of neonatal morbidity was similar in the two groups.\n In post-term pregnancy, the induction of labor results in a lower rate of cesarean section than serial antenatal monitoring; the rates of perinatal mortality and neonatal morbidity are similar with the two approaches to management.", "To compare induction of labor at gestational age 41 weeks with expectant management in regard to neonatal morbidity. Secondary aims were to assess the effect of these managements on mode of delivery and maternal complications.\n Between September 2002 and July 2004, postterm women with singleton cephalic presentation and no prelabor rupture of membranes were randomly assigned to induction of labor at 289 days or antenatal fetal surveillance every third day until spontaneous labor. Main outcome measures were neonatal morbidity, operative delivery rates, and maternal complications.\n Five hundred eight women were randomly assigned, 254 in each group. No differences of clinical importance were observed in women in whom labor was induced compared with women who were expectantly managed with regard to the following outcomes: neonates whose 5-minute Apgar score was less than 7 (three neonates in the induction group compared with four in the monitoring group, P=.72); neonates whose umbilical cord pH was less than 7 (three compared with two, P=.69); prevalence of cesarean delivery (28 compared with 33, P=.50); or prevalence of operative vaginal delivery (32 compared with 27, P=.49). In the induction group more women had precipitate labors (33 compared with 12, P<.01; number needed to treat was 13), and the duration of second stage of labor was more often less than 15 minutes (94 compared with 56, P<.01; number needed to treat was 7).\n No differences were found between the induced and monitored groups regarding neonatal morbidity or mode of delivery, and the outcomes were generally good.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00385229.\n I.", "nan", "In a prospective randomised study of mothers referred for prolonged pregnancy (around the 42nd week) 214 (group 1) were submitted to attempted induction of labour and 195 (group 2) assigned to continue for a further week without intervention. Strict selection criteria were used for the certainty of term. Mothers in group 2 were given regular non-stress tests to ensure fetal wellbeing, as were those in group 1 in whom induction failed. In group 1, 48 (23%) out of 210 first attempted inductions failed. In group 2, 135 (69%) of the births started spontaneously as compared with 38 (18%) in group 1. The mean duration of labour was 7.5 hours in each group. There was no significant difference in incidence of operative delivery, use of analgesics, or signs of perinatal asphyxia. Significantly more children in group 1 needed phototherapy for hyperbilirubinaemia. There was a clustering of births in the late afternoon and evening, which was most pronounced in group 1. A policy of vigilant non-intervention up to the 44th completed week of pregnancy does not appear to jeopardize mother or fetus.", "nan", "To determine maternal and perinatal morbidity and the spontaneous labor rate beyond 41 weeks of gestation.\n Patients with uncomplicated pregnancy were recruited at 41 weeks and screened for fetal or maternal well-being. Following observation between 41 and 42 weeks, patients were randomized to either serial monitoring by cardiotocography and measurement of amniotic fluid index, or to immediate induction. Comparisons were made using the chi(2) test. Results after 42 weeks were analyzed according to intention at randomization.\n Morbidity was not increased before 42 weeks. After 42 weeks, the cesarean section rate and incidence of meconium below the vocal cords were increased in monitored patients. The median gestational age in patients who were monitored was 298.5 (294-321) days. In patients observed from 41 weeks, 91.6% labored spontaneously.\n It is reasonable to observe uncomplicated pregnancy until 42 weeks with adequate monitoring. After 42 weeks, induction of labor is preferred.", "To compare the obstetric outcome of induction of labor at 41 weeks and of follow-up until 42 weeks and induction if the patient has still not given birth at 42 weeks.\n Six hundred women at 287+/-1 days of gestation with definitely unfavorable cervical scores were randomized to labor induction (N=300) or spontaneous follow-up (N=300) with twice-weekly nonstress testing and amniotic fluid measurement and once-weekly biophysical scoring. The treatments used in the induction group were (1) vaginal administration of 50 microg misoprostol (n=100), (2) oxytocin induction (n=100), and (3) transcervical insertion of a Foley balloon (n=100). The primary outcome measures were the cesarean delivery rate, whether or not the normal hospital stay had to be extended, and the neonatal outcomes. Secondary outcome measure included number of emergency cesarean deliveries performed for abnormalities of the fetal heart rate (FHR).\n The abdominal delivery rate was 19.3% in the induction group and 22% in the follow-up group (p=0.4). The mean length of hospital stay in the two main groups was 1.4+/-0.8 days and 1.3+/-1 days, respectively (p=0.1). Significantly higher rates of macrosomia and shoulder dystocia were seen in the follow-up group (24.6 and 2.3%) than in the induction group (7.6%, p<0.001; 0.3%, p=0.03). Meconium-stained amniotic fluid and meconium aspiration syndrome were observed significantly less frequently in the induction group (9.3 and 1.3%) than in the follow-up group (20.3%, p<0.001; 4%, p=0.03). Rates of emergency abdominal delivery in response to worrying FHR traces, neonatal intensive care unit admission, and low umblical artery pH were similar in the two groups. There was one intrauterine fetal death in the follow-up group.\n Induction of labor at 41 weeks of gestation does not increase the cesarean delivery rate or cause a longer stay in hospital than follow-up until 42 weeks, and neonatal morbidity is also lower after induction.", "In a prospective randomized study, pregnancies with unfavorable cervix and well established gestational age of at least 42 weeks were selected for management by either antepartum fetal testing or prostaglandin gel induction of labor. Of the 108 pregnancies studied, 57 (53%) had labor induced and 51 (47%) continued without intervention. Comparison of the two groups showed no difference in meconium staining, fetal distress, length of first stage of labor, the need for intervention, or the mode of delivery. In terms of Apgar score the neonatal outcome was not significantly different but a greater proportion of the babies (7.8% versus 1.8%) in the noninduced group required intubation. Our data show that there is no particular advantage in letting the pregnancy go beyond 42 completed weeks of gestation especially if prostaglandin is available for induction of labor.", "The two methods of management of prolonged pregnancy, induction of labour and expectant management with foetal surveillance, have pros and cons. Therefore, we compared the induction of labour with serial antenatal foetal monitoring in the management of post-term pregnancy.\n Seventy-four women with uncomplicated pregnancy at 41 weeks (287 days) of gestation were randomly assigned to undergo either induction of labour or serial antenatal foetal monitoring. Labour was induced in the latter group whenever there was evidence of foetal compromise. Antenatal monitoring consisted of the foetal kick count, non-stress test and biophysical profile.\n Fifty-seven per cent of women went into spontaneous labour by 41 weeks and 4 days (291 days) of gestation and only 14% developed foetal compromise before that. However, when the gestational age was more than 41 weeks and 4 days (291 days), the incidence of meconium staining of amniotic fluid and evidence of uteroplacental insufficiency increased significantly. The rate of caesarean section, instrumental delivery, foetal distress and duration of labour did not differ significantly between the two groups.\n The policy of inducing labour at 41 weeks and 4 days (291 days of gestation) in uncomplicated pregnancies is justified in our population. However, foetal monitoring should begin at 41 weeks of gestation.", "Three hundred two low-risk obstetric patients with an unfavorable cervical examination and well-established gestational age of at least 287 days were randomly selected for management by either antepartum fetal testing or prostaglandin gel cervical ripening followed by aggressive induction of labor and delivery. The patients managed by induction of labor had a lower incidence of meconium-stained amniotic fluid, meconium aspiration, low Apgar scores, postmaturity syndrome, fetal distress, and cesarean delivery than did patients managed with antepartum fetal testing. Our data suggest that prostaglandin gel cervical ripening and induction of labor and delivery by 42 weeks' gestation may be the most appropriate management for patients with well-established gestational age and an unfavorable cervical examination.", "In a prospective, randomised trial, 111 obstetrically normal pregnant women, who had elective induction of labour performed between 39 and 40 weeks, were compared with 117 controls who were managed expectantly until 41 weeks. Compared with the controls, the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery. The mean length of labour, the amount of pethidine used, and the Apgar scores at 1 minute were similar in the two groups. In the electively induced group, the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls, but the differences were mot statistically signficant. The hour of delivery was similar in the two groups, suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour. There was no evidence that the hazards to mother and child were increased by elective induction, and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths.", "Management of the uncomplicated pregnancy prolonged beyond the estimated date of confinement is controversial, particularly when the cervix is unfavorable for induction. The benefit of reducing potential fetal risk with induction of labor must be balanced against the morbidity associated with this procedure. The objective of this study was to compare two strategies for managing postterm pregnancy (i.e., immediate induction and expectant management).\n Four hundred forty patients with uncomplicated pregnancies at 41 weeks' gestation were randomized to either immediate induction of labor (n = 265) or expectant management (n = 175). Patients with expectant management underwent nonstress testing and amniotic fluid volume assessment twice per week. Patients in the induction group underwent induction within 24 hours of randomization. To evaluate the efficacy of intracervical prostaglandin E2 gel, patients in the induction group were randomized in a 2:1 scheme to receive either 0.5 mg prostaglandin E2 gel or placebo gel intracervically 12 hours before induction of labor with oxytocin.\n The incidence of adverse perinatal outcome (neonatal seizures, intracranial hemorrhage, the need for mechanical ventilation, or nerve injury) was 1.5% in the induction group and 1% in the expectant management group (p > 0.05). There were no fetal deaths in either group. There were no differences in mean birth weight or the frequency of macrosomia (birth weight > or = 4000 gm) between the two groups (p > 0.05). Regardless of parity, prostaglandin E2 intracervical gel was not more effective than placebo in ripening the cervix. The cesarean delivery rate was not significantly different in the expectant (18%), prostaglandin E2 gel (23%), or placebo gel (18%) groups.\n Adverse perinatal outcome in otherwise uncomplicated pregnancies of > or = 41 weeks is very low with either of the management schemes described. Thus from the perspective of perinatal morbidity or mortality either management scheme is acceptable.", "Our purpose was to determine the optimal management of pregnancies beyond 41 week's gestation with a cervix unfavorable for induction.\n All uncomplicated pregnancies that reached 41 weeks'gestation with a Bishop score of< or =4, were randomly assigned to one of two groups\n The duration of labor was shorter in the group \"prépidil\" compared with the control group (P=0.002). Identification of an unfavorable cervix at 41 weeks was unlikely to change by 42 weeks and cervical ripening was required in 40% cases. There was no significant difference in caesarean section rates. Rates of admission into the neonatal unit and fetal outcomes were similar in the two groups.\n Cervical ripening with prostaglandin gel at 41 week's gestation for uncomplicated singleton pregnancies is safe and should be advocated.", "To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks.\n Randomized controlled trial of induction of labor at or shortly after the 42-week limit, versus close monitoring without induction except when indicated for medical reasons.\n Hospital's obstetrical department\n 188 pregnant women, randomly allocated to two groups with 94 in each.\n Induction of labor by stripping of membranes and i.v. oxytocin infusion, with artificial rupture of membranes when the cervical opening was 3 cm or more in diameter. The control group was followed with clinical, biochemical and electronic tests, intervention being applied according to needs.\n Frequency and modes of operative delivery, maternal and perinatal morbidity and mortality.\n The distribution of gestational age (in weeks) at birth was almost identical in the two groups, but there were more operative deliveries in the control group than in the induction group (64 versus 48, p less than 0.05). Maternal complications and perinatal morbidity rates were equally distributed between the groups. There was one perinatal death in the induction group and two deaths among the controls.\n With due reservation for small numbers, routine induction after term may result in fewer operative deliveries. No other advantage has been demonstrated when compared with close monitoring and intervention when medically indicated." ]

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[ "Comprehesiven clinical studies with thiothixene.", "A study of chlorpromazine: methodology and results with chronic semi-disturbed schizophrenics.", "The effect of chlorpromazine on serum cholesterol in chronic schizophrenic patients.", "Schizophrenia treated with and without chlorpromazine.", "Evaluation of trifluperidol in chronic schizaphrenia.", "Chlorpromazine in chronic schizophrenic women: I. Experimental design and effects at maximum point of treatment.", "Are there schizophrenics for whom drugs may be unnecessary or contraindicated?", "Prediction of relapse in schizophrenic outpatients treated by drug and sociotherapy.", "Psychological effects of single-dose antipsychotic medication.", "Chlorpromazine used with an intensive occupational therapy program; a controlled study.", "A controlled comparative investigation of the effects of promazine, chlorpromazine, and a placebo in chronic psychosis.", "A placebo-controlled comparison of zotepine versus chlorpromazine in patients with acute exacerbation of schizophrenia.", "Propranolol in schizophrenia. I. Comparison of propranolol, chlorpromazine and placebo.", "Family interaction patterns, drug treatment, and change in social aggression.", "A comparison of thioridazine, trifluoperazine, chlorpromazine, and placebo: a double-blind controlled study on the treatment of chronic, hospitalized, schizophrenic patients.", "Acute paranoid schizophrenia. (Treatment with chlorpromazine, trifluoperazine and placebo).", "Comparative study of TPS-23, chlorpromazine and placebo in chronic schizophrenic patients.", "Prophylactic effect of neuroleptics in symptom-free schizophrenics.", "Chlorpromazine in schizophrenic withdrawal and in the withdrawn schizophrenic.", "Does sigma receptor antagonism predict clinical antipsychotic efficacy?", "A controlled clinical study of chlorpromazine and reserpine in chronic schizophrenia.", "Premorbid asocial adjustment and response to phenothiazine treatment among schizophrenic inpatients.", "Parenteral haloperidol for rapid control of severe, disruptive symptoms of acute schizophrenia.", "LONG-TERM FOLLOW-UP STUDY OF SCHIZOPHRENIC PATIENTS.", "The immediate effects of chlorpromazine in newly admitted schizophrenic patients.", "Chlorpromazine and the untreated chronic schizophrenic: a long-term trial.", "Drug treatment in newly admitted schizophrenic patients.", "Evaluation of loxapine succinate in chronic schizophrenia.", "Phenothiazine effects on psychological and psychophysiological dysfunction in chronic schizophrenics.", "PHENOTHIAZINES IN PREVENTION OF PSYCHIATRIC HOSPITALIZATION. 3. DELAY OR PREVENTION OF HOSPITALIZATION.", "Effects of chlorpromazine on primary-process thought manifestations.", "The relative efficacy of vespral and chlorpromazine in the treatment of a group of chronic schizophrenic patients.", "Evaluation of butaclamol in chronic schizophrenic patients.", "The comparative effectiveness of six phenothiazine compounds, phenobarbital and inert placebo in the treatment of acutely ill patients: global measures of severity of illness." ]

[ "nan", "nan", "nan", "nan", "nan", "nan", "This study reports that there are schizophrenics who do relatively well long term without the routine or continuous use of antipsychotic medication. Specially selected young males undergoing an acute schizophrenic episode were followed, after hospitalization, for up to three years. While hospitalized they were assigned randomly to either placebo or chlorpromazine treatment. Many unmedicated-while-in-hospital patients showed greater long-term improvement, less pathology at follow-up, fewer rehospitalizations and better overall function in the community than patients who were given chlorpromazine while in the hospital. Factors related to post-hospital outcome were good premorbid history and short-lived paranoid characteristics. Considerations which may have an effect on the successful management of acute schizophrenic patients not on medication are mentioned. The findings underline the need for further study of how to utilize antipsychotic medication more selectively in the treatment of schizophrenia.", "Despite the established efficacy of neuroleptics for maintaining schizophrenics in the community, there are data suggesting that those with very good prognostic signs may do as well without drugs. In testing this, we find no evidence that patients with good signs are not in need of drugs; instead they profit most from drug treatment. Patients who benefit little (1) are men whose families were disrupted earlier in their lives, (2) live alone or with extended families whose attitudes toward the study are not positive, and (3) are irregular in taking their medication. The practical implication is that the drug nonresponder can be helped by some means to ensure regularity of medication taking, such as a visiting nurse or long-acting medication. A second research question is whether major role therapy (MRT, a combination of social casework and vocational rehabilitation) can lengthen the time until relapse. Major role therapy affected time to relapse in a disordinal manner; asymptomatic patients benefited from MRT, while in patients with greater symptom severity MRT- suprisingly--hastened relapse. It is hypothesized that symptomatic patients are suffering from an inability to manage an expanded and enriched cognitive field; MRT, a therapy that urges the patient to become more responsible and to expand his horizons, may actually induce a state with which the patient cannot cope. It is recommended that a therapy such as MRT be deferred until the patient is essentially asymptomatic.", "nan", "nan", "nan", "The aim of this study was to evaluate the efficacy of zotepine in the treatment of acute episodes of schizophrenia.\n Patients with acute exacerbation of schizophrenia (DSM-III-R criteria; n = 158) were allocated on a random, double-blind basis to receive zotepine (150 or 300 mg/day), chlorpromazine (300 or 600 mg/day) or placebo for 8 weeks. Symptoms were assessed on the BPRS, SANS and CGI scales at baseline and weeks 1, 2, 4, 6 and 8 and patients were assessed at these times for adverse effects. Analysis was by analysis of variance on the intent-to-treat population, with last observation carried forward.\n Mean BPRS scores improved statistically significantly more with zotepine than chlorpromazine (point estimate of difference -12.4, 95% CI -18.3 to -6.5) or placebo (point estimate of difference -12.7, 95% CI -18.6 to -6.8). Zotepine produced significantly fewer extrapyramidal symptoms (EPS) than chlorpromazine.\n Zotepine is an effective antipsychotic with low propensity for EPS.", "Fifty-three hospitalized chronic schizophrenic patients were treated with either propranolol, chlorpromazine or placebo in a double-blind randomized trials for up to three months. Propranolol in a usual dose of 640 mg/day, produced marked cardiovascular effects but no improvement in schizophrenic symptomatology relative to placebo. The effects of chlorpromazine were small and inconsistent.", "nan", "nan", "nan", "nan", "Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the \"first assigned drugs\" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics.", "nan", "The psychotogenic actions of sigma receptor agonists, such as pentazocine, have led to the hypothesis that sigma receptor antagonists may be putative antipsychotic agents. In this study, BW234U, a selective but relatively weak sigma receptor antagonist was compared at two different dosage ranges with chlorpromazine and placebo in a double-blind randomized treatment trial in schizophrenic patients undergoing acute exacerbation. During the 4-week blinded treatment period, there was a modest drop in Brief Psychiatric Rating Scale (BPRS) score in the chlorpromazine group, however, neither dosage range of BW234U, nor placebo produced a significant drop in the BPRS. Our results suggest that BW234U is an ineffective anti-psychotic agent in schizophrenics experiencing acute exacerbation of their illness. Due to BW234U's relatively weak antagonism at the sigma recognition site, this does not rule out the possibility that more potent and equally selective sigma antagonists may possess antipsychotic efficacy.", "nan", "nan", "Intramuscular haloperidol, at three dose levels, (5 mg, 2 mg, and 1 mg) chlorpromazine (25 mg), and placebo were compared for efficacy, rapidity of therapeutic onset, and safety in 50 acute psychotic patients requiring rapid control. The drugs were administered parenterally under double-blind conditions at half-hour intervals until successful control of moderate to very severe symptomatology was achieved or a maximum of four injections had been given. Global evaluation, BPRS, and target symptom ratings were performed. The overall results indicated that the 5 mg and 2 mg haloperidol doses were significantly superior to the 1 mg haloperidol and 25 mg chlorpromazine doses and to placebo. Transfer of patients to oral haloperidol was satisfactorily accomplished. Side effects for all medications were minimal and included slight to moderate EPS and drowsiness. The use of antiparkinson drugs completely controlled the extrapyramidal symptoms.", "nan", "To evaluate the clinical effectiveness of chlorpromazine in comparison with placebo over a brief period of hospitalization, the authors conducted a double-blind study of the drug in 44 acutely ill schizophrenic patients. These patients had been newly admitted to a brief treatment unit where the average length of stay was 7 to 10 days. The results of this study indicate that chlorpromazine had no more calming or antipsychotic effect than placebo during the first 5 days of treatment. The authors suggest that 5 days is too short a time for a clinical trial to gauge patient response to chlorpromazine.", "nan", "nan", "nan", "This study examined the effects of phenothiazine treatment on attentional-perceptual, cognitive, and psychophysiological dysfunction in chronic schizophrenics. Under double-blind conditions, 20 patients receiving chlorpromazine and 20 receiving placebo for eight weeks were tested by performance measures, clinically rated, and monitored for skin resistance and heart rate on four occasions. Phenothiazine effects on measures of attention-perception and on psychophysiological response were demonstrable, but not on tests and ratings of cognitive dysfunction. The direction of effects was toward normalization of function. Drug treatment tended to improve ability to sustain set, to increase efficiency of selective attention, and to increase rate of information processing. Autonomic reactivity was reduced and a deactivation effect suggested. Clinical improvement was correlated with reduction in attentional dysfunction. The results are discussed in terms of their implications for hypothesized behavioral mechanisms of drug action, primary \"behavioral site\" of drug action, therapeutic response measurement, and functional theories of schizophrenic psychopathology.", "nan", "nan", "nan", "In a double-blind, placebo-controlled study, an attempt was made to evaluate butaclamol in chronic schizophrenic patients using chlorpromazine (CPZ) as the standard comparative drug. With doses up to 50 mg/day, butaclamol was shown to have significant antipsychotic activity comparable to CPZ but with a much higher incidence of extrapyramidal signs. A more reasonable maintenance dose may be in the range of 5 to 20 mg/day. Rebound insomnia was noted again with butaclamol, which warrants further study.", "nan" ]

[ "8792266", "7608035", "17610057", "10755175" ]

[ "The long-term effects of auditory training on children with autism.", "Brief report: a pilot study of auditory integration training in autism.", "Brief report: the effects of Tomatis sound therapy on language in children with autism.", "Auditory integration training for children with autism: no behavioral benefits detected." ]

[ "Eighty children, 3-17 years of age, with autism or Asperger syndrome and mild to severe distress in the presence of some sounds, were randomly allocated to two groups. The experimental group received auditory training and the control group listened to the same unmodified music under the same conditions. Significant improvements in behavior and severity of autism were maintained for 12 months by both groups. Informal data suggested that a range of abnormal responses to sound and other sensory abnormalities may also have improved. Verbal and performance IQ increased significantly 3 to 12 months after interventions. Findings suggest that some aspect of both auditory training and listening to selected unmodified music may have a beneficial effect on children with autism and sound sensitivity, and indicate a need for further research into the effects that led to these changes and the mechanisms involved in the sensory abnormalities commonly associated with autism.", "nan", "Due to the myriad of problems associated with autism, parents often consider alternative treatments. The investigation was undertaken to determine the effects of the Tomatis Method on language skills in children with autism utilizing a randomized, double-blind, placebo-controlled, crossover design. The results indicated that although the majority of the children demonstrated general improvement in language over the course of the study, it did not appear to be related to the treatment condition. The percent change for Group 1 (Placebo/Treatment) for treatment was 17.41%, and placebo was 24.84%. Group 2 (Treatment/Placebo) showed -3.98% change for treatment and 14.15% change for placebo. The results reflect a lack of improvement in language using the Tomatis Method for children with autism.", "Auditory integration training and a control treatment were provided for 16 children with autism in a crossover experimental design. Measures, blind to treatment order, included parent and teacher ratings of behavior, direct observational recordings, IQ, language, and social/adaptive tests. Significant differences tended to show that the control condition was superior on parent-rated measures of hyperactivity and on direct observational measures of ear-occlusion. No differences were detected on teacher-rated measures. Children's IQs and language comprehension did not increase, but adaptive/social behavior scores and expressive language quotients decreased. The majority of parents (56%) were unable to report in retrospect when their child had received auditory integration training. No individual child was identified as benefiting clinically or educationally from the treatment." ]

[ "10834894" ]

[ "Preventing dog bites in children: randomised controlled trial of an educational intervention." ]

[ "nan" ]

[ "8497353", "7947499", "10731", "677195", "3554055", "3893132", "16828100", "3736600", "5895", "453276", "3536631", "7294080" ]

[ "A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation.", "Intermittent versus continuous electronic monitoring in labour: a randomised study.", "Controlled trial of fetal intensive care.", "An assessment of continuous fetal heart rate monitoring in labor. A randomized trial.", "A randomized trial of electronic fetal monitoring in preterm labor.", "The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring.", "Intrapartum electronic fetal monitoring vs. intermittent auscultation in postcesarean pregnancies.", "A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies.", "The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy.", "A controlled trial of the differential effects of intrapartum fetal monitoring.", "Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: a controlled clinical trial.", "A controlled trial of fetal heart rate monitoring in a low-risk obstetric population." ]

[ "To determine whether continuous intrapartum electronic fetal heart rate monitoring (EFM) is associated with decreased perinatal mortality and morbidity compared with intermittent auscultation.\n The study was conducted simultaneously at two university hospitals in Athens, Greece (Alexandra and Marika Iliadi Hospitals) from October 1, 1990 to June 30, 1991. All patients with singleton living fetuses and gestational ages of 26 weeks or greater were eligible for inclusion. The participants were assigned to continuous EFM or intermittent auscultation based on the flip of a coin. Both groups were followed during labor according to the most recent ACOG guidelines. However, fetal scalp blood pH and crossover from one group to the other were not used.\n A total of 1428 patients were included, 746 in the EFM group and 682 in the auscultation group. There were no differences between the groups in terms of maternal age, gravidity, parity, gestational age, and number of antepartum high-risk factors. More patients monitored electronically received oxytocin for either augmentation (52.4 versus 38.1%; P = .0001) or induction (15.6 versus 7%; P = .0001). The length of labor was longer in the EFM group (first stage 6.1 +/- 4.3 versus 5.5 +/- 3.7 hours; P = .006; second stage 29.4 +/- 18.6 versus 26.9 +/- 16.9 minutes; P = .01). There was a higher incidence of nonreassuring fetal heart rate patterns in the EFM group (23.4 versus 10.7%; P = .0001) and a higher rate of surgical intervention (11.2 versus 4.8%; P = .0001). This difference pertained to both vacuum extraction (5.8 versus 2.4%; P = .002) and cesarean delivery for suspected fetal distress (5.3 versus 2.3%; P = .005). There were no differences in 1- and 5-minute Apgar scores, fetal acidosis at birth, need for neonatal resuscitation, neonatal intensive care unit admission, use of assisted ventilation, neonatal hospital stay, or any other neonatal complications. Two neonatal deaths occurred in the EFM group and nine perinatal deaths in the auscultation group (two intrapartum and seven neonatal deaths). The perinatal mortality rates were 2.6 per 1000 and 13 per 1000 total births, respectively (P = .04). The two deaths in the EFM group and three of the neonatal deaths in the auscultation group may not have been prevented by intrapartum monitoring; however, four neonatal deaths from the auscultation group occurred in depressed (5-minute Apgar scores less than 7), acidotic (cord artery pH at or below 7.13) infants. The perinatal death rate related to fetal hypoxia was significantly less in the EFM group (zero of 746 versus six of 682; P = .03).\n In this controlled trial, intrapartum EFM, as the primary and only method of intrapartum fetal surveillance, was associated with decreased perinatal mortality due to fetal hypoxia but also with higher rates of surgical intervention for suspected fetal distress.", "To compare the efficacy in detecting signs of fetal hypoxia in labour of intermittent (I-group) versus continuous (C-group) electronic fetal monitoring in women with low or moderate risk factors for fetal distress.\n A prospective, randomised study.\n A tertiary referral centre.\n Four thousand and forty-four parturients at low risk for obstetric complications with a reactive fetal heart rate admission test at arrival in labour. During the study period (October 5 1989 to May 31 1991), 5647 women were delivered in the labour ward. Of these, 1178 women (20.9%) were excluded because of high risk factors in pregnancy or at admission for labour, including women undergoing elective caesarean section. Of the remaining 4469 women 4044 (90.5%) were randomised to either intermittent (n = 2015) or continuous monitoring (n = 2029) during the first stage of labour.\n In the C-group the fetal heart rate was recorded continuously with electronic fetal monitoring during the first stage of labour. In the I-group the fetal heart rate was recorded with electronic fetal monitoring for 10 to 30 min every 2 to 2.5 h during the first stage of labour, and the fetal heart rate was auscultated every 15 to 30 min in between recording periods. If complications occurred, recording was changed to continuous. In the second stage of labour all the women were monitored continuously. Umbilical cord artery acid-base status was assessed at birth.\n Duration of electronic fetal monitoring, rates of abnormal fetal heart rate patterns, caesarean section for fetal distress, acidosis in umbilical cord arterial blood at birth, Apgar scores of less than 7 at 1 or 5 min, and referrals to the neonatal intensive care unit.\n There were no significant differences between the study groups in the incidence of ominous fetal heart rate recordings: 6.3% (I-group) versus 6.6% (C-group), or the interval from arrival to first detected abnormal fetal heart rate, although the number of suspicious fetal heart rate patterns was higher in the C-group (28.6%) than in the I-group (24.6%). In the I-group electronic fetal monitoring was performed for (median monitoring time) 38.8% of the first stage of labour as compared with 78.6% in the C-group. The incidence of caesarean section for fetal distress was similarly low in both groups: 1.2% versus 1.0%. There were no significant differences in the immediate neonatal outcome in terms of umbilical artery pH, Apgar scores, or admissions to the neonatal care unit.\n Intermittent use of electronic fetal monitoring at regular intervals (with stethoscopic auscultation in between) appears to be as safe as continuous electronic fetal monitoring in low risk labours.", "A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified.", "Intrapartum continuous fetal heart rate monitoring has been routinely performed at the Jessop Hospital for Women for some years. However, no controlled trials had ever been performed to show its advantages over intermittent auscultation in low-risk patients. A prospective randomized study of 504 patients compared continuous fetal heart rate monitoring with intermittent auscultation. There was no significant difference between the two groups in neonatal deaths, Apgar scores, maternal and neonatal morbidity, and cord blood gases. The cesarean section rate was significantly increased (p less than 0.05) in the monitored patients but this did not seem attributable to fetal monitoring. No beneficial or deleterious effects of continuous fetal heart rate monitoring in labor were shown.", "Intrapartum electronic fetal heart rate (FHR) monitoring and fetal blood gas sampling were compared with periodic auscultation of FHR in a multicentered randomized trial of preterm singleton pregnancies with fetal weights of 700-1750 g. Two hundred forty-six pregnancies were studied (electronic FHR monitoring N = 122, auscultation N = 124). Perinatal or infant death was associated with 14% of pregnancies with electronic FHR monitoring and 15% with auscultation. No significant differences were noted in the prevalence of low five-minute Apgar scores, intrapartum acidosis, intracranial hemorrhage, or frequency of cesarean section (P greater than .10). Compared with electronic FHR monitoring, intrapartum auscultation as done in this study is unlikely to be associated with detectable differences in perinatal outcomes within the high-risk setting of preterm labor.", "In a randomized controlled trial involving 12,964 women, a policy of continuous electronic intrapartum fetal heart monitoring was compared with an alternative policy of intermittent auscultation, both policies including an option to measure fetal scalp blood pH. Women allocated to electronic fetal heart monitoring had shorter labors and received less analgesia. The caesarean delivery rates were 2.4% for electronic fetal heart monitoring and 2.2% for intermittent auscultation but this small difference arose from the identification of nearly twice as many fetuses with low scalp pH (less than 7.20) in the electronic fetal heart monitoring group. The forceps delivery rate was 8.2% in the electronic fetal heart monitoring group compared with 6.3% in the intermittent auscultation group, and this excess was explained by more instrumental deliveries prompted by fetal heart rate abnormalities. There were 14 stillbirths and neonatal deaths in each group, with a similar distribution of causes. There were no apparent differences in the rates of low Apgar scores, need for resuscitation, or transfer to the special care nursery. Cases of neonatal seizures and persistent abnormal neurological signs followed by survival were twice as frequent in the intermittent auscultation group, and this differential effect was related to duration of labor. Follow-up at 1 year of babies who survived neonatal seizures revealed three clearly abnormal infants in each group. The implications of these findings for both theory and practice are discussed.", "nan", "We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Predominant risk factors included oxytocin stimulation of labor, dysfunctional labor, abnormal fetal heart rate, or meconium-stained amniotic fluid. This prospective alternate-month clinical trial took place over a 36-month period during which 34,995 women gave birth. In alternate months, either 7 (for \"selective monitoring\") or 19 (for \"universal monitoring\") fetal monitors were made available in the labor and delivery unit. During the \"selective\" months, 6420 of 17,409 women (37 percent) were electronically monitored, as compared with 13,956 of 17,586 women (79 percent) during the \"universal months.\" Universal monitoring was associated with a small but significant increase in the incidence of delivery by cesarean section because of fetal distress, but perinatal outcomes as assessed by intrapartum stillbirths, low Apgar scores, a need for assisted ventilation of the newborn, admission to the intensive care nursery, or neonatal seizures were not significantly different. We conclude that not all pregnancies, and particularly not those considered at low risk of perinatal complications, need continuous electronic fetal monitoring during labor.", "Intrapartum electronic fetal heart rate monitoring of the high-risk obstetric patient is thought to improve the perinatal outcome. A prospective randomized study of 483 high-risk obstetric patients in labor was carried out comparing the effectiveness of electronic fetal monitoring with auscultation of fetal heart tones. The infant outcome was measured by neonatal death, Apgar scores, cord blood gases, and neonatal nursery morbidity. There were no differences in the infant outcomes in any measured category between the electronically monitored group and the auscultated group. The cesarean section rate was markedly increased in the monitored group (16.5 vs. 6.8 per cent in the auscultated patients). The presumptive benefits of electronic fetal monitoring for improving fetal outcome were not found in this study.", "A controlled prospective study of the differential effects of intrapartum fetal monitoring on mothers and infants has been conducted at Denver General Hospital, Denver, Colorado. A total of 690 high-risk obstetric patients in labor were randomly assigned to one of three monitoring groups--auscultation, electronic fetal monitoring alone, or electronic monitoring with the option to scalp sample. There were no differences in immediate infant outcomes in any measured category (Apgar scores, cord blood gases, neonatal death, neonatal morbidity, nursery course) among the three groups. There were no differences in rates of infant or maternal infections. The cesarean section rate was markedly increased in the electronically monitored groups, especially in the electronically monitored alone (18%) as compared with the auscultated (6%) (P less than 0.005). In this controlled trial electronic monitoring did not improve neonatal outcomes and the mothers were at increased risk of cesarean section.", "In a prospective clinical randomized investigation 487 women had the condition of the fetus during labour supervised by means of stethoscope (AUS), while 482 women went through labour under surveillance of electronic fetal monitoring, cardiotocography (EFM). 349 women refused to participate in the investigation (NAI) and had delivery conducted according to the normal procedures of the department (70% AUS, 30% EFM). Significantly more pathological fetal heart rate patterns (FHR) were found in the EFM group compared to the AUS group in both the first and the second stage of labour. As a result significantly more vacuum extractions were performed in the EFM group than in the AUS group, while no statistical difference was found between the groups in the incidence of acute cesarean sections carried out for asphyxia. One case of intrapartum death occurred in the AUS group. No differences were found in Apgar scores after 1 and 5 min or in neonatal morbidity at examination on the 2nd and 5th days after delivery. A tendency towards more biochemically compromised children was found in the AUS group. The specificity for both methods was found to be acceptably high (80%), while the predictive value for both methods was low (50%). More research is therefore urgently needed to evaluate supplementary investigations and parameters for the evaluation of the intrapartum fetal condition.", "A controlled trial of fetal heart rate (FHR) monitoring in a low-risk obstetric population was carried out in 989 patients at the Mercy Maternity Hospital and Queen Victoria Medical Centre. The use of monitoring failed to demonstrate any improvement in perinatal outcome. Monitoring was associated with an increased intervention rate and a small increase in the number of babies who remained in the isolette beyond 3 days. This study does not support the view that FHR monitoring should be used in all labors. Further study in a larger sample is recommended." ]

[ "3786037", "7049013", "9449495", "7439516", "3511936", "17075269", "8160567", "6810863", "3537092", "6788244", "65508", "8516087", "7003383", "7047707", "6791596", "2662130", "6435085", "13835085", "9164358", "108152", "8760776", "3535686", "8175622", "6653683", "3315687", "6775752", "2179367", "6346833", "7056011", "3365858" ]

[ "Behavior abnormalities and poor school performance due to oral theophylline use.", "Comparison of the long-term effect of fenoterol hydrobromide and theophylline syrups in pre-school asthmatic children.", "Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group.", "A comparative trial of slow-release aminophylline, salbutamol and a half dose combination in the prevention of childhood asthma.", "Once daily theophylline in childhood asthma.", "A randomized open-label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children.", "Study of the effects of treatment with theophylline on the cognitive process and behaviour of children with bronchial asthma.", "Comparison of nebulised sodium cromoglycate and oral theophylline in controlling symptoms of chronic asthma in pre-school children: a double blind study.", "Extrapulmonary effects of maintenance therapy with theophylline and inhaled albuterol in patients with chronic asthma.", "Nocturnal wheezing in children: management with controlled-release aminophylline.", "Comparison of cromoglycate (cromolyn) and theophylline in controlling symptoms of chronic asthma. A collaborative study.", "Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children.", "The value of maintenance theophylline in steroid-dependent asthma.", "Comparison of orally administered metaproterenol and theophylline in the control of chronic asthma.", "Nebulised cromoglycate, theophylline, and placebo in preschool asthmatic children.", "Slow-release terbutaline and theophylline for the long-term therapy of children with asthma: a Latin square and factorial study of drug effects and interactions.", "A double-blind study comparing the effectiveness of cromolyn sodium and sustained-release theophylline in childhood asthma.", "Choline theophyllinate in children with asthma: a controlled trial.", "Salmeterol versus theophylline in the treatment of asthma.", "Monitoring response to bronchodilator therapy in asthma in childhood.", "Fluticasone propionate compared with theophylline for mild-to-moderate asthma.", "Slow release theophylline in preschool asthmatics.", "Administration of half-dose theophylline together with ketotifen to asthmatic children--a double-blind, placebo-controlled study.", "Long-term treatment of children with sustained-release theophylline.", "A once daily theophylline preparation in prevention of nocturnal symptoms in childhood asthma.", "Controlled trial of cromoglycate and slow-release aminophylline in perennial childhood asthma.", "Long-term, double-blind comparison of controlled-release albuterol versus sustained-release theophylline in adolescents and adults with asthma.", "A controlled comparison of slow-release theophylline, ketotifen and placebo in the prophylaxis of asthma in young children.", "A comparison of metaproterenol and theophylline for control of childhood asthma.", "Need for theophylline in severe steroid-requiring asthmatics." ]

[ "Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 micrograms/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.", "Eleven asthmatic children less than six years were treated double-blind for eight weeks with fenoterol, theophylline or placebo syrups. Both active drugs significantly decreased the incidence of cough compared to placebo. Nocturnal symptoms and wheezes were also reduced but were not improved to a statistically significant degree.", "Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma.\n We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray.\n A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 microg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements.\n Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed.\n Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/ benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children.", "The effect of slow-release aminophylline, salbutamol and a half dose combination of both was compared in children with chronic asthma. Drugs were given over three consecutive 5-week periods during which patients recorded daily peak flow measurements and symptom scores. At the end of each treatment period pulmonary function tests were done. Sixteen of twenty-nine children completed the trial satisfactorily and their results have been used for analysis. The data show slow-release aminophylline and salbutamol to be equally effective and the half dose combination as effective as either drug alone. The results suggest there may be a therapeutic advantage in combining a beta 2 agonist with theophylline when high doses of either drug alone are not fully effective or when toxic effects occur.", "A new sustained-release theophylline preparation has been designed with the purpose of providing 24-hour protection against bronchospasm in asthmatics when given as a single dose. Fifteen children with moderate asthma completed a double-blind, placebo-controlled crossover trial of this product given once a day before bed. There was a significant fall in night symptoms (P less than 0.05), a rise in the mean early morning peak expiratory flow rate (PEFR) (P less than 0.01) and a fall in the number of mornings on which PEFR was less than 2 SD under the mean for height (P less than 0.01). An improvement in mean day symptom scores and evening PEFR was not significant. Thus we have shown that this product given once a day before bed is suitable for this way.", "Inhaled corticosteroids (ICSs) are widely used in combination with other classes of drugs for treatment of childhood asthma. The efficacy and the safety of montelukast added to low-dose ICS therapy were compared with those of sustained-release theophylline added to low-dose ICS therapy in asthmatic children in the present study.\n Following the 2-week run-in period, 6-to 14-year old patients receiving treatment with ICSs were randomized to treatment for 4 weeks with either montelukast 5 mg once daily or sustained release theophylline 5-8 mg/kg (dry syrup) or 100-200 mg (tablet) twice daily. Patients also received a fixed dose of ICS throughout the run-in and treatment periods. The primary efficacy endpoint was the change from baseline in peak expiratory flow (PEF) at Week 2.\n A significant increase in morning PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 2 (change from baseline of 22.8 L/minvs. 8.7 L/min; p = 0.041 for between-group difference) and at Week 4 (31.0 L/minvs. 9.8 L/min; p = 0.012). A significant increase in evening PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 4 (24.7 L/minvs. 8.7 L/min; p = 0.027). There were no significant differences between the treatment groups in incidences of clinical and laboratory adverse experiences.\n The results indicate that montelukast added to low-dose ICS is an effective and safe option for the treatment of asthma in children.", "The effects of theophylline (T) on cognitive and emotional aspects were evaluated in nine children with mild bronchial asthma (7-14 years). The study was double blind crossover against placebo (P) for a period of 30 days for each. The children admitted to the study had an average IQ (80-101) and were able to perform pulmonary function studies (PFS). On days 0, 30 and 60 patients were evaluated by psychological tests (Wisc, Bender, Complex Figure A. Rey and Miss Goodenough/Machouver). PPS an T serum levels were performed on days 15 and 45. During the T period all patients had T serum levels greater than 5 mcg/ml (5 to 22). The final evaluation showed no changes in the psychological tests. Behaviour alterations were not reported by the parents. In conclusion, in this group of patients there was no influence of T on the asthmatic children's behavior. These results are in agreement with the recent data published by Schlieper et al. (J. Pediatr. 118: 449-455, 1991).", "The efficacy of nebulised sodium cromoglycate and an oral theophylline solution at currently recommended doses were compared in one to six-year-old children with chronic asthma. Twenty-six children completed a 24-week double-blind trial of treatment with sodium cromoglycate (SCG), theophylline and a combination of both. The three regimens were administered, each for eight weeks, in a random sequence. SCG was administered by inhalation as a nebulised solution in standard doses of 20 mg qid and serum drug concentrations were recorded. Theophylline was given as liquid aminophylline. Dosage was individualised with the assistance of serum theophylline measurements and averaged 6.1 mg/kg/dose q6h. Patients had an average of 61% symptom-free days while on SCG and combination regimens, compared with only 46.5% for days free of symptoms when on theophylline alone (p less than 0.05). There was significantly less use of supplementary medication for acute symptoms (p less than 0.05) when on the combination of SCG and theophylline. No regimen was more frequently associated with symptoms of exercise intolerance or decreased appetite. Numerous adverse side effects to theophylline were recorded, but none were recognised with SCG. SCG is at least as effective as theophylline in controlling asthmatic symptoms in the 1-6-year-old age group.", "The extrapulmonary effects of slow-release theophylline and an inhaled beta 2-agonist (albuterol) were examined separately and in combination among 18 adults and adolescents with asthma during a 3-month randomized, double-blind, crossover trial. Although neither global impressions nor daily diaries revealed differences in adverse effects, a structured questionnaire completed at the end of each regimen suggested a small but statistically significant increase in nausea and depressive and caffeine-like symptoms during the theophylline-containing regimens. Theophylline was also associated with improved verbal learning but decreased motor steadiness. Metabolic effects associated with theophylline included lower serum bicarbonate, greater urinary calcium excretion, and higher serum calcium, uric acid, and creatinine. Albuterol was associated with lower neutrophil counts and lower serum theophylline concentrations. There were no drug-induced effects on cardiac rhythm.", "nan", "28 children with chronic asthma (15 in Denver and 13 in London) completed a 12 wk double-blind trial of treatment with sodium cromoglycate (cromolyn sodium), theophylline, and a combination of both. The three regimens were administered, each for 4 wk, in random sequence as part of a collaborative investigation of the relative efficacy of the two antiasthmatic agents. Cromoglycate was administered by inhalation in standard doses of 20 mg q.i.d. Theophylline dosage was individualized with the assistance of serum-theophylline measurements and averaged 6 mg/kg/dose q.i.d. (range 3-8--8-5 mg/kg/dose). Peak expiratory-flow rates measured twice daily on all patients averaged 75% of that predicted during cromoglycate administration, 79% during theophylline, and 81% during the combined-drug regimen (P less than 0.05). Patients had an average of 59% of days free of symptoms while on cromoglycate and 71% of days symptom-free when on both the theophylline and the combination regimens (P less than 0.025). None of the 13 patients whose asthmatic symptoms were previously controlled with cromoglycate was unable to complete the 4 wk trial with theophylline alone; 1 patient whose symptoms had been previously controlled with theophylline twice developed severe asthmatic symptoms while receiving cromoglycate, and he had to be withdrawn from that study period. No significant differences in adverse effects of the medication were observed during the 12 wk trial.", "To compare the benefits and adverse reactions of theophylline and beclomethasone (BDP) in the long-term control of mild to moderate chronic asthma in children.\n Multicentered, double-blind, double-placebo, randomized, controlled trial.\n One hundred ninety-five children between the ages of 6 and 16 years with mild to moderate asthma.\n Treatment with either BDP, 84 micrograms four times a day, or sustained-release theophylline administered twice daily in doses adjusted for optimum control of symptoms.\n Daily diary record of symptoms, peak flow rates, supplemental bronchodilator and glucocorticoid treatment, doctor and hospital visits, absence from work and school, and side effects.\n Aerosol BDP and sustained-release theophylline were effective primary treatments for mild to moderate chronic asthma. Beclomethasone resulted in comparable symptom control with less bronchodilator use and fewer courses of systemic steroids than did theophylline. Side effects were observed significantly more frequently with theophylline than with BDP. Growth velocity suppression was noted with BDP and was more pronounced in boys. Suppression was not associated with alterations in cortisol measurements either at baseline or following stimulation.\n Both theophylline and BDP are effective therapy for mild to moderate asthma. Caution must be used with the administration of BDP in children because of possible growth velocity suppression.", "We examined the value of maintenance theophylline at serum concentrations of 10 to 20 micrograms per milliliter in a placebo-controlled, randomized, double-blind trial of 33 children with steroid-dependent chronic asthma. Patients were free of all symptoms 63 +/- 6 per cent of the days (mean +/- S.E.M.) when taking theophylline as compared with 42 +/- 6 per cent when taking placebo (P < 0.01). Inhaled metaproterenol was required twice as often with placebo (P < 0.01), and additional daily corticosteroids were needed more than three times as often with placebo (P = 0.02). Daily peak flow measurements improved with theophylline (P < 0.01) as did monthly spirometric measurements and residual volume measured by plethysmography. Theophylline was associated with a 50 per cent increase in the number of patients able to complete an exercise test (P = 0.01) and with a smaller decrease in forced expiratory volume in one second among patients completing the exercise (P < 0.02). We conclude that maintenance bronchodilator therapy with theophylline can provide clinically important benefit for patients with chronic steroid-dependent asthma.", "The efficacy of metaproterenol (orciprenaline) and theophylline given orally at currently recommended doses was examined in 34 children with chronic asthma using a randomized double-blind cross-over evaluation of four weeks' duration for each active regimen. No serious adverse effects were seen with either medication, but tremor occurred more frequently with metaproterenol (P less than 0.01). No significant differences were observed in the frequency of nausea, vomiting, headache, or insomnia (P greater than 0.05). Symptoms of wheezing, coughing, exercise intolerance, and interference with sleep were more frequently associated with the oral metaproterenol regimen; completely asymptomatic days occurred 50% more frequently in association with theophylline therapy (P less than 0.01). Mean peak flows, performed twice daily during each of the four-week study periods, were 86 and 92% of predicted for metaproterenol and theophylline, respectively (P less than 0.05). Pulmonary function decreased significantly less with theophylline than with metaproterenol among those who completed six minutes of treadmill exercise during both regimens (P less than 0.05). Corticosteroids, used for acute symptoms that failed to respond to the addition of inhaled metaproterenol, were required in four patients during both regimens, in ten patients only during the metaproterenol regimen, and in one patient only during the theophylline regimen (P less than 0.02). Thus, theophylline therapy was associated with fewer adverse effects, fewer symptoms of asthma, better pulmonary function, better exercise tolerance, and less requirements for corticosteroids than was treatment with metaproterenol.", "Sixteen children aged under 5 years with chronic asthma completed a double-blind crossover trial of treatment with oral choline theophyllinate (6.7 mg/kg four times daily) and nebulised sodium cromoglycate (20 mg four times daily). The trial comprised three 8-week treatment periods during which active sodium cromoglycate, active choline theophyllinate, and placebo were given in random order. Symptom scores for sleep disturbance, cough, wheeze, and daily activities were similar during the three treatment periods if results were analysed using Friedman's non-parametric analysis of variance. However the Mantel-Haenszel test showed that sodium cromoglycate was superior to placebo (P less than 0.05) in maintaining normal daily activities. Either regimen is safe and well tolerated by young children.", "To evaluate the long-term effects of slow-release formulations of theophylline and terbutaline on pulmonary function, clinical symptoms, and side effects, 24 children with stable and moderately severe perennial asthma participated in a prospective double-blind cross-over study. The patients and the treatments were randomized according to the Latin square design to eliminate all possible period/climate biases throughout the protracted study period. The treatments consisted of terbutaline, 5 mg, theophylline, 200 mg, the combination, and placebo, given twice daily orally and crossing over every 28 days. The two drugs, administered alone or in combination, improved lung function and symptoms when compared with placebo. The interaction of theophylline and terbutaline was quantitatively shown by 2 x 2 factorial statistical design to be essentially additive rather than synergistic in the control of asthma. No increase in side effects was noted when the combined therapy was used. These findings suggest therapeutic advantages to combining submaximal oral doses of sustained-release theophylline and terbutaline for the long-term treatment of children with asthma.", "The effectiveness of cromolyn sodium and theophylline on asthma in children was compared during a 3-month trial. Forty-six children (aged 5 to 15 years) with asthma were assigned at random to cromolyn or theophylline (Theo-Dur) treatment groups. Each subject received theophylline placebo or cromolyn placebo in addition to the active drugs. A methacholine challenge test was done at the start of the study to document asthma and was repeated during the third month. The theophylline dosage was regulated to obtain serum levels of 10 to 15 micrograms/mL by a physician not involved directly with patient care. Forty patients completed the study. Both theophylline and cromolyn treatment groups showed improvement from base-line status in terms of symptom scores, pulmonary function, and decreased use of inhaled albuterol. Patients treated with theophylline had more side effects and required more frequent office visits than those treated with cromolyn. Both groups had decreased sensitivity to methacholine, and for one statistical test patients treated with cromolyn improved significantly. These results indicate that cromolyn is as effective as theophylline in treating mild to moderate asthma in children; additional benefits were fewer side effects and a possible decrease in bronchial hyperactivity.", "nan", "Although theophylline is recommended by current guidelines for the management of asthma in patients with persistent symptoms, theophylline has a narrow therapeutic index, requiring individual dose titration and regular monitoring of serum theophylline concentrations to avoid adverse effects.\n To compare the inhaled long-acting bronchodilator, salmeterol, with the oral bronchodilator, theophylline, in the maintenance treatment of asthma.\n In two multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group studies, patients received salmeterol aerosol 42 micrograms, extended-release theophylline capsules, or placebo twice daily for 12 weeks.\n Of 638 adult and adolescent patients with moderate asthma who entered the prebaseline theophylline titration period, 154 were withdrawn prior to randomization (71 due to theophylline-related adverse effects); 484 patients comprised the intent-to-treat population. The mean serum theophylline concentration measured approximately seven hours postdose during the titration period in the theophylline group was 12.7 mg/L (70 mumol/L). The same dose during the treatment period resulted in a mean serum theophylline concentration between 7.6 to 7.9 mg/L (42-44 mumol/L) when measured approximately 12 hours postdose. Salmeterol was significantly more effective than theophylline or placebo in improving mean morning PEF over the entire 12 weeks (P < or = .02). Mean predose FEV1 improved significantly with salmeterol compared with placebo (P < .001); there was no difference between theophylline and placebo. Salmeterol was also significantly more effective than theophylline or placebo (P < .02) in improving asthma symptoms, reducing nighttime awakenings, and reducing the daily use of albuterol. After 12 weeks of treatment, patients in the salmeterol group expressed significantly greater overall satisfaction with their asthma medication than did patients who received theophylline (P < .01). Patients in the theophylline group experienced more gastrointestinal adverse events than did patients in the salmeterol group (P < .05).\n Salmeterol, 42 mg twice daily, was better tolerated and significantly more effective than extended-release theophylline twice daily in the maintenance treatment of asthma.", "Recently there has been increased interest in the role of bronchodilators in the maintenance therapy of asthma in childhood. We report the use of slow-release aminophylline (Phyllocontin Continus tablets) in childhood asthma. Ten patients, all of whom were receiving disodium cromoglycate (DSG), were given a single dose of Phyllocontin tablets (12.5 mg/kg) and observed over a period of 8 hours. Measurements of peak flow rate (PFR) and forced expiratory volume in one second (FEV1) showed an increase of at least 30% at 3 to 5 hours and the improvement continued to 8 hours. No effect was noted on heart rate. Ten patients were assessed over a 4-week period on DSG then over two 4-week periods on Phyllocontin tablets and placebo on a double-blind crossover basis. The dosage of Phyllocontin tablets used was 12.5 mg/kg twice daily. Using twice daily PFR recordings there was no significant difference between the two periods on DSG and Phyllocontin tablets. The reduction in PFR during the period on placebo was significant, however, and more markedly so between the period of placebo and the period on Phyllocontin tablets. We conclude that Phyllocontin tablets in these patients compared favourably with DSG in the maintenance therapy of asthma in childhood. The results obtained after single dose administration also suggest that a proportion of children with asthma may benefit from combined treatment with DSG and regular bronchodilators.", "The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma.\n The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma.\n In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms.\n Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%).\n Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.", "A double blind crossover trial with active or placebo slow release theophylline (Slo-phyllin) in children with asthma aged up to 4 years is described. Although no difference in symptom scores was shown, other differences in favour of active treatment were noted. We conclude that this preparation is of benefit in the management of the wheezing preschool child. The value of symptom scores as an index of clinical improvement is discussed.", "Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 micrograms/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T+K-Placebo (T group); T+K (T+K group); half-dose T+K (T/2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T+P, T+K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.", "After one year of sustained-release theophylline (SRT) treatment, 19 children with severe perennial asthma participated in a 6-week, placebo-controlled, randomized, double-blind cross-over study. The severity of their asthma was evaluated before SRT-treatment (pre-period) and one year later, both during the theophylline period and the placebo period of the double-blind study. Compared with the pre-period, all observed parameters, except the number of extra bronchodilators required, were statistically significantly improved in the placebo period of the double-blind trial performed after one year. In addition, except for peak expiratory flow measured at home and the number of acute attacks, all parameters were significantly improved during the theophylline period when compared with placebo treatment. During this study, mean serum theophylline level was 13.3 mg/l (range 7.8-19.4 mg/l). The results show that theophylline remains efficient after one year's administration. The much better control of the children's asthma following one year of treatment emphasizes the need for regular re-evaluation of children receiving continuous prophylactic treatment.", "Twenty school children with chronic asthma who despite regular prophylactic therapy continued to have troublesome nocturnal wheeze or cough entered a double-blind cross-over study in which a once daily theophylline preparation was compared with placebo to assess control of these symptoms. Seventeen children completed both phases of the study. Significant improvement was noted in the day and night symptom scores, the morning dip index and daily peak flow readings with a significant reduction in rescue bronchodilator inhaler usage during the active treatment period. Satisfactory serum theophylline concentrations were obtained 11-12 h post dose in all children using a standard dose of 18 mg/kg per day at 2000 hours. Three children were withdrawn because of minor side-effects. The theophylline preparation studied in conjunction with other conventional anti-asthma therapy was thus effective in controlling nocturnal symptoms.", "nan", "This parallel-group study compared the safety and efficacy of controlled-release albuterol versus sustained-release theophylline, both administered every 12 hours. One hundred twenty-four adolescent and adult patients with asthma and with chronic reversible obstructive airway disease were studied. All patients qualified with an FEV1 less than or equal to 80% of predicted (not receiving treatment) and greater than or equal to 15% reversibility in FEV1 or greater than or equal to 25% reversibility in FEF25-75% after inhaled isoproterenol. All patients were known to be able to take theophylline without unacceptable adverse effects. Theophylline was titrated for patients to receive, unblinded, theophylline serum concentrations of 10 to 20 micrograms/ml. With subsequent randomization, 62 patients continued to receive theophylline and 62 patients started taking albuterol in the 12-week, double-blind, double-dummy portion of the study. Pulmonary function was measured during a pretreatment visit (unmedicated) and serial assessment was made starting just before the morning dose and continuing for 12 hours after the dose at the end of 1, 6, and 12 weeks of treatment. Both treatment groups exhibited statistically significant increases in FEV1 from the pretreatment visit to all times of observation at weeks 1, 6, and 12. The increases in FEV1 were not significantly different between albuterol and theophylline administration. There was no evidence of tolerance to the bronchodilatory effect during 12 weeks in either treatment group. Only one patient in the study stopped treatment because of an adverse effect. This patient had tremor during albuterol administration. All other adverse events were tolerated or resolved during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "A double blind crossover comparison of slow-release theophylline, ketotifen and placebo was carried out in 18 young children with perennial asthma. Theophylline significantly reduced symptoms and increased the mean peak expiratory flow rate. Transient nausea and vomiting was commoner during theophylline treatment but did not usually necessitate discontinuance of therapy.", "Twenty asthmatic children who had daily wheezing requiring constant medication as outpatients were given oral metaproterenol or oral theophylline in a randomized double-blind crossover study. Each medication was given for four weeks, after the theophylline dosage necessary to give a therapeutic level was established. Pulmonary function parameters, daily peak-flow measurements and diary symptom scores were statistically comparable in most patients during these four-week intervals. Metaproterenol may be used in place of oral theophylline for at least a four-week interval with no decrease in effectiveness.", "Concern about side-effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi-medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti-asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in-patients, 12-15 years old, completed a double-blind, cross-over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long-acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10-30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids." ]

[ "11865833", "15300074" ]

[ "Treatment of vascular retinal disease with pentoxifylline: a controlled, randomized trial.", "Accelerated reperfusion of poorly perfused retinal areas in central retinal artery occlusion and branch retinal artery occlusion after a short treatment with enhanced external counterpulsation." ]

[ "The aim of this study was to evaluate the effect of PXF (1800 mg daily) in patients with sudden loss of vision (SLV) in a 4-week trial, evaluating clinical outcome and retinal flow parameters. Inclusion criteria were SLV associated with thrombosis of the retinal artery; decrease in retinal blood flow (PSF: peak-systolic flow; EDF: end-diastolic flow velocity) and asymmetry between the two retinal arteries (>40%) documented by duplex scanning. All 10 included patients completed the study. The groups were comparable. No side effects were reported. A significant improvement in flow velocity (p<0.05) and a decrease in analogue score in both groups were observed. PSF increase was 550% in the PXF group vs 288% in the placebo group (262% difference). EDF increase was 400% in the PXF group vs 200% in the placebo group (200% difference). There was a significant difference in the analogue score decrease (33.3% difference larger in the PXF group; p<0.05). In conclusion, PXF treatment improved retinal flow after retinal artery occlusion better than placebo and should be considered as an important option in this condition.", "To date, no satisfactory therapy has become available for patients with acute central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO). Enhanced external counterpulsation (EECP) is a new noninvasive procedure that increases perfusion of inner organs. In the current study, the authors measured the impact of EECP on reperfusion in ischemic retinal tissue.\n In a prospective, randomized study, 20 patients with CRAO or BRAO were included. Ten patients were given hemodilution therapy and 2 hours of EECP, and 10 patients were given regular hemodilution therapy only. Quantification of changes in retinal perfusion was carried out by means of scanning laser Doppler flowmetry (in arbitrary units).\n Enhanced external counterpulsation caused no observable adverse events. A significant increase in perfusion occurred immediately after EECP in the ischemic retinal areas (57 +/- 19 arbitrary units versus 99 +/- 14 arbitrary units). In contrast, no change was measured in the group not treated with EECP (83 +/- 19 arbitrary units versus 89 +/- 44 arbitrary units). Forty-eight hours later, a significant increase in perfusion could be shown in the ischemic retina of both groups, and no significant difference of perfusion was found between the two groups any longer.\n The current study suggests that EECP could be a clinically useful and safe procedure in patients with CRAO or BRAO to accelerate recovery of perfusion in ischemic retinal areas." ]

[ "17452166", "15993860", "15814161", "16566626", "10926942", "8171171", "1557484", "8202964", "19406291", "18311826", "8891089", "12638027", "3521524", "12169073", "3881418", "8018452", "12789682", "18653034", "9892304", "9501747", "10698809", "3901675", "15232328", "19092112", "10834419", "2221162", "18164939", "9283926", "9632030", "6141377", "17244833", "17846258", "15960563", "11138997", "7915270", "10534546", "8894194", "9565715" ]

[ "A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure.", "A randomized trial of citalopram versus placebo in outpatients with asthma and major depressive disorder: a proof of concept study.", "An evaluation of efficacy and safety of reboxetine in elderly patients affected by \"retarded\" post-stroke depression. A random, placebo-controlled study.", "A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.", "Fluoxetine in early poststroke depression: a double-blind placebo-controlled study.", "Structured group therapy and fluoxetine to treat depression in HIV-positive persons.", "Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease.", "Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram.", "A randomized controlled trial of sertraline for the treatment of depression in persons with traumatic brain injury.", "Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study.", "The effect of fluoxetine on anxiety and depression symptoms in cancer patients.", "Early fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up.", "Doxepin treatment of depressed patients with chronic obstructive pulmonary disease.", "Sertraline treatment of major depression in patients with acute MI or unstable angina.", "Trimipramine in physical illness with depression.", "The effect of low dose lofepramine in depressed elderly patients in general medical wards.", "SSRIs in the treatment of depression in Parkinson's disease.", "Trazodone therapy of the post-stroke depression.", "Fluoxetine treatment for depression in patients with HIV and AIDS: a randomized, placebo-controlled trial.", "Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients.", "Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study.", "Efficacy and safety of mianserin in the treatment of depression of women with cancer.", "Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial.", "A controlled trial of antidepressants in patients with Parkinson disease and depression.", "Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial.", "Antidepressant pharmacotherapy of depression associated with multiple sclerosis.", "Efficacy of paroxetine in treating major depressive disorder in persons with multiple sclerosis.", "Placebo-controlled treatment trial of depression in elderly physically ill patients.", "Treatment of major depression in HIV-seropositive men. HIV Neurobehavioral Research Center Group.", "Nortriptyline treatment of post-stroke depression: a double-blind study.", "Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial.", "Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine.", "Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression.", "Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial.", "Effects of fluoxetine on mood and immune status in depressed patients with HIV illness.", "The effects of dothiepin on subjects with rheumatoid arthritis and depression.", "Pharmacological treatment of depression in cancer patients. A placebo-controlled study of mianserin.", "Fluoxetine in depressed patients on dialysis." ]

[ "Depression is frequently observed in patients with heart failure and is associated with poor quality of life and adverse prognosis. However, the prevalence of depression in heart failure could be overestimated because symptoms of depression overlap with those of heart failure. Similarly, the importance of depression may be overestimated if depression merely reflects worse heart failure. Because the response to depression treatment has not been evaluated in this patient population, we evaluated the efficacy of controlled-release paroxetine (paroxetine CR), a selective serotonin reuptake inhibitor, on depression and quality of life in chronic heart failure.\n A double-blind, randomized, placebo-controlled design was used to evaluate reductions in depression following 12 weeks of treatment with paroxetine CR (n = 14, age 62.1 +/- 12.3 years) or placebo (n = 14, age = 61.9 +/- 9.0 years). Patients with symptomatic congestive heart failure and a score of at least 10 on the Beck Depression Inventory (BDI) were eligible. Beck Depression Inventory was obtained at baseline and 4, 8, and 12 weeks of follow-up. Quality of life was assessed using the Medical Outcomes Study Short Form and the Minnesota Living with Heart Failure Questionnaire.\n Controlled-release paroxetine resulted in significantly more recovery from depression (BDI <10) than placebo (69% vs 23%, P = .018) and resulted in lower continuous BDI scores throughout the intervention (P = .024). Controlled-release paroxetine was associated with higher general health levels compared with placebo on the Medical Outcomes Study 36-Item Short Form survey (38 +/- 10 vs 30 +/- 6, P = .016) at 12 weeks of follow-up. Reductions in depression were correlated with improvements in psychological aspects of quality of life (P < .05) but not with physical quality of life measures (P > .10).\n Antidepressant therapy with paroxetine CR results in significant reductions in depression among patients with heart failure. The reductions in depression with paroxetine CR are accompanied by improvements in psychological aspects of quality of life. Larger controlled trials are needed to further document the effectiveness of paroxetine CR and other selective serotonin reuptake inhibitors in patients with heart failure and to determine patient subgroups that are most likely to benefit from antidepressive interventions.", "The prevalence of asthma has increased in recent years and depression is common in this population. Minimal data are available on the treatment of depressed asthma patients.\n Ninety adults with asthma and current major depressive disorder were randomized to receive citalopram or placebo for 12 weeks. At each visit, the Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology - Self-Report, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire were administered, and oral corticosteroid use assessed.\n In the evaluable sample (n = 82), the primary outcome, a random regression analysis of HRSD scores, revealed no significant between-group differences. Bonferroni corrected secondary outcomes revealed HRSD scores decreased significantly in both groups with a significantly greater decrease in the citalopram group at week 6. Changes in asthma symptoms were similar between groups. The groups had similar rates of oral corticosteroid use at baseline, but the citalopram group had less corticosteroid use during the study. Changes in asthma symptom severity correlated with changes in depressive symptom severity.\n A reduction in depressive symptoms was associated with improvement in asthma. Corticosteroid use, an important measure of severe asthma exacerbations, was lower in the citalopram group. Larger clinical trials in this population are warranted.", "Depression occurs frequently in post-stroke patients and appears to be associated with an impairment in their rehabilitation and functional recovery. Although selective serotonin reuptake inhibitors (SSRI) are often used in post-stroke depression (PSD), it has been observed that only a subset of patients is responsive to this treatment. Other patients respond to tricyclic antidepressants or MAO inhibitors, which, however, may not have a favorable profile of safety and tolerability in post-stroke patients. In this double-blinded, placebo-controlled study, we evaluated the efficacy and tolerability of the noradrenaline reuptake inhibitor, reboxetine, in a subset of PSD patients classified as affected by \"retarded\" depression. Reboxetine (4 mg, twice daily, for 16 weeks) was administered to patients that developed depression after a single ischaemic or hemorrhagic stroke. We assessed the severity of depressive symptoms by the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). HDRS and BDI scores (mean+/-S.D.) at baseline were, respectively, 24+/-1.31 and 19.87+/-1.46 in the placebo group, 24.06+/-1.52 and 20.56+/-2.16 in the reboxetine group. After 16 weeks, HDRS and BDI mean scores were respectively 22.73+/-2.4 and 18.4+/-3.33 in the placebo group, 9.26+/-2.15 and 8.06+/-3.43 in the reboxetine group [p<0.01 versus the respective baseline (paired t-test); (#)p<0.01 versus retarded depressed patients treated with placebo (one-way analysis of variance (ANOVA) applied to the difference from baseline, associated with Dunnett's t-test to isolate the differences)]. Reboxetine showed a good efficacy, safety and tolerability in PSD patients affected by \"retarded\" depression. We conclude that reboxetine is well tolerated and may be a useful therapeutic option in PSD patients with \"retarded\" depression.", "This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV.\n In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score.\n Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups.\n The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.", "Early poststroke depression (PSD) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients. This trial was designed to study the efficacy and tolerance of fluoxetine (FLX) in the treatment of early PSD.\n This was a multicenter, double-blind, placebo-controlled study. Recent hemiplegic patients (<3 months) suffering from major depressive disorder (determined by International Classification of Diseases, 10th Revision, and Montgomery-Asberg Depression Rating Scale [MADRS] >19) were randomized to receive either 20 mg/d fluoxetine (FLX) or placebo for 6 weeks. Patients were evaluated by use of the Motricity Index, Mini-Mental State Examination, Functional Independence Measure, and MADRS. Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 (baseline) and days 15, 30, and 45 (end point).\n Of 121 patients screened, 31 were included in the study, 16 in the FLX group and 15 in the placebo group. There were no significant differences in baseline characteristics among the 2 groups. The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point (11.8+/-6. 7 [mean+/-SD] versus 18.7+/-10.0, respectively; P=0.05). FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate (62.5% versus 33.3%, respectively) and greater mean decrease of MADRS (16.6 versus 8.4, respectively; P=0.02). There were no differences in motor, cognitive, or functional improvement and no significant side effects after FLX treatment, except for a patient with a moderate and transient increase of transaminases.\n FLX is an efficacious and well-tolerated treatment for early PSD. Further research is needed to evaluate the efficacy and safety of long-term treatment in this population.", "In 1990, 20 asymptomatic persons diagnosed with the human immunodeficiency virus (HIV-positive) and mild-to-moderate depression were divided into 2 comparison groups. One group received structured group therapy plus fluoxetine, while the other received the same therapy plus a placebo. Affective, neurocognitive, and immune variables were measured before and after the intervention. In the patients receiving group therapy and fluoxetine, its administration did not improve treatment outcome compared to the therapy and placebo group. No significant differences between the two groups were noted on immune variables. However, symptoms of depression decreased in both groups, and both groups showed significant incorporation of the skills in active behavioral coping taught in therapy.", "Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.", "The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated.\n A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups.\n Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat analysis, P < .05) and excluding patients who dropped out during the first 3 weeks (efficacy analysis, P < .005). Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke. No serious side effects related to the treatment were detected; those present were mild and usually transient.\n This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective.", "To examine the efficacy of sertraline in the treatment of depression after traumatic brain injury (TBI).\n Double-blind, randomized controlled trial.\n Research center at a major urban medical center.\n Subjects were a referred and volunteer sample of 52 participants with TBI, a diagnosis of major depression disorder (MDD), and a score on the Hamilton Rating Scale for Depression (HAM-D) of 18 or greater. The majority of the sample was male (58%), had less than 14 years of education (73%), had incomes below $20,000 (82%), and were from minority backgrounds (75%). Approximately one third of the sample had mild brain injuries, and two thirds had moderate to severe brain injuries. The mean age was 47+/-11, and the mean time since injury was 17+/-14 years. One participant withdrew from the study because of side effects.\n Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg) or placebo for 10 weeks.\n The HAM-D, the Beck Anxiety Inventory, and the Life-3 quality of life (QOL).\n No statistically significant differences were found at baseline between drug and placebo groups on baseline measures of depression (24.8+/-7.3 vs 27.7+/-7.0), anxiety (16.4+/-12.3 vs 24.0+/-14.9), or QOL (2.96+/-1.0 vs 2.9+/-0.9). The income level of those receiving placebo was significantly lower than those participants receiving medication. Analyses of covariance revealed significant changes from preintervention to posttreatment for all 3 outcome measures (P<.001) but no group effects. Random-effects modeling did not find any significant difference in patterns of scores of the outcome measures between the placebo and medication groups.\n Both groups showed improvements in mood, anxiety, and QOL, with 59% of the experimental group and 32% of the placebo group responding to the treatment, defined as a reduction of a person's HAM-D score by 50%.", "Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short-term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short-term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double-blind, randomized, placebo- controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short-term clinical advantage.\n (c) 2008 Movement Disorder Society.", "Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients. A double-blind placebo-controlled study was therefore designed to assess the effectiveness of 20 mg fluoxetine. Of 115 cancer patients who fulfilled entry criteria for levels of distress, 45 patients were randomized to a fluoxetine treatment group (FA) and 46 patients to a placebo group (PA) after a 1-week placebo period designed to exclude placebo responders. The Montgomery and Asberg Depression Scale (MADRS), the Hamilton Anxiety Scale (HAS), the Hospital Anxiety and Depression Scale (HADS), the Revised Symptom Checklist (SCL90-R) and the Spitzer Quality of Life Index (SQOLI) were used to assess the efficacy of fluoxetine. The response rate, defined by a HADS score lower than 8 after 5 weeks of treatment, was not significantly higher in the FA group (11%) compared to the PA group (7%). Compared to the PA group, patients in the FA group showed a significantly greater decrease in SCL90-R mean total score after 5 weeks, but not a greater decrease in HADS mean score. No difference between the two groups was found in observer-reported assessments (MADRS, HAS and SQOLI). Significantly more drop-outs were observed in the FA group (n = 15) than in the PA group (n = 7), although the frequencies of side-effects were not significantly different.", "Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients.\n This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment.\n 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected.\n The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe.", "During each of two six-week treatment periods, 12 depressed outpatients with chronic obstructive pulmonary disease received increasing doses of doxepin hydrochloride or a placebo as tolerated. The mean maximal doses of doxepin hydrochloride and placebo were 105 and 128 mg, respectively. Three of the 12 patients dropped out because of doxepin's side effects. The depression and anxiety scores at the end of the treatment periods were virtually identical and not significantly different from baseline scores. Changes in the 12-minute walking distance were more closely correlated with changes in the depression and anxiety scores than with changes in the forced expiratory volume in 1 s or forced vital capacity. Thus, doxepin is ineffective in treating depressed patients with chronic obstructive pulmonary disease; improvements in the 12-minute walking distance were closely correlated with improvements in the depression or anxiety scores.", "Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.\n To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions.\n Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001.\n A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%).\n After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks.\n The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD.\n Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline.\n Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.", "To assess whether tricyclic antidepressants are useful in patients with a serious physical disorder who develop symptoms of major depression, 42 medically ill outpatients who met RDC criteria for endogenous major depression and had a Raskin depression score of at least 7 were studied. The patients were randomly assigned to a 6-week trial of trimipramine or placebo under double-blind conditions. In the placebo group, depressive symptoms improved when the physical disorder improved; in the trimipramine group, improvement was seen in the depressive symptoms even when there was no concomitant improvement in physical condition.", "A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.", "nan", "The incidence of depression following a hemispheric stroke ranges from 25 to 60%. The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known. We studied subjects both with and without evidence of depression, as indicated by any one of three criteria: (i) Clinical diagnosis of depression, (ii) Abnormal Zung-depression score. (iii) Abnormal dexamethasone suppression test (DST). Patients in a stroke rehabilitation program (22) were randomized to receive either placebo or 300 mg/day trazodone-HCl, beginning 30 days after the stroke. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living (ADL) scores, with antidepressant therapy, as compared to patients receiving placebo. An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone, i.e., in post-stroke depression such a treatment seems to be beneficial.", "The goals of this study were to determine whether fluoxetine is superior to placebo in treating HIV-seropositive patients with major depression or dysthymia or both, whether severity of immunosuppression is associated with treatment response, and whether fluoxetine treatment is associated with change in immune status as measured by CD4 cell count.\n A double-blind, randomized, placebo-controlled 8-week trial of fluoxetine was conducted in a university-affiliated research outpatient clinic. The fluoxetine-placebo randomization was 2:1. All patients were offered 4 months of additional open treatment. Main outcome measures included the Clinical Global Impression, Hamilton Depression Rating Scale, and CD4 cell count.\n Of 120 patients randomly assigned to fluoxetine or placebo, 87 completed 8 weeks of treatment. In the total group, 51% had AIDS. All but three were men, 35% were nonwhite, and 6% had intravenous drug use as a risk factor. In an intention-to-treat analysis, 57% of fluoxetine patients and 41% of placebo patients were responders. Among patients who completed the study, 74% responded to fluoxetine and 47% to placebo; this difference was statistically significant. Severity of immunosuppression was not related to antidepressant response, attrition, or side effects, and fluoxetine treatment was not associated with change in CD4 cell count.\n Fluoxetine is an effective antidepressant in the context of HIV illness. However, both placebo response and attrition were substantial, suggesting both that nonspecific factors may be more salient and that yet another medication (i.e., an antidepressant) may be less acceptable among patients with serious medical illness already requiring multiple concomitant medications.", "This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection.\n Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12.\n Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%).\n Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.", "This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke.\n A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind randomized study comparing nortriptyline, fluoxetine, and placebo over 12 weeks of treatment. The majority of patients were recruited from a rehabilitation hospital in Des Moines, Iowa, but other enrollment sites were also used. Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression. Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks. Response to treatment of depression for individual patients was defined as a greater-than-50% reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression. Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial, compared with patients treated with placebo, on measures of impairment in activities of daily living and levels of cognitive and social functioning.\n Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression, in improving anxiety symptoms, and in improving recovery of activities of daily living as measured by the Functional Independence Measure. There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients. Fluoxetine in increasing doses of 10-40 mg/day led to an average weight loss of 15. 1 pounds (8% of initial body weight) over 12 weeks of treatment that was not seen with nortriptyline or placebo.\n Given the doses of medication used in this study, nortriptyline was superior to fluoxetine in the treatment of poststroke depression. Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients, alternative measurement scales, or the optimal time of treatment.", "Depression is a major complication of cancer. The efficacy and safety of mianserin were evaluated in a randomized placebo-controlled trial of 73 depressed women with cancer. According to RDC diagnosis, all patients showed situational major depression. Both groups were well matched for cancer localization, clinical stages, Karnofsky scores, duration of depression, baseline values on the Hamilton Depression Rating Scale (HDRS), Zung Self-Rating Depression Scale (ZSRDS), and Clinical Global Impression of Illness Severity (CGI-S), and for type of depression, whether dominantly depressive or depressive-anxious. Between days 7-21, there were significantly fewer dropouts with mianserin (7) than with placebo (15). When compared with placebo, there were significant improvements for mianserin for HDRS on days 7, 21 and 28, for ZSRDS on days 7 and 28, and for CGI-S on days 7, 14, 21 and 28. According to Clinical Global Impression of Illness Improvement (CGI-I) there were significantly more responders with mianserin (28) than with placebo (18). The efficacy index for mianserin was significantly greater than for placebo on days 21 and 28. At the end of the trial the scores for HDRS sleep disturbance factor and HDRS anxiety-somatization factor were significantly reduced for mianserin than for placebo. There were no significant differences in side-effects between treatment groups. It is concluded that mianserin is superior to placebo in reducing the severity and duration of depression which is present especially in patients with advanced cancer.(ABSTRACT TRUNCATED AT 250 WORDS)", "While testosterone's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature, no placebo-controlled trial selecting for depressive disorders and including a standard antidepressant has been conducted. Accordingly, this double-blind trial was designed to determine whether testosterone, as well as fluoxetine, is superior to placebo for depression, fatigue, or both.\n One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depressive disorder entered the 8-week trial and were randomized to testosterone (up to 400 mg IM testosterone cypionate biweekly), fluoxetine (up to 60 mg/d), or double placebo. Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue, the Hamilton Rating Scale for Depression, and the Chalder Fatigue Scale.\n Ninety men completed the trial. In intention-to-treat analyses, mood response rates were 54%, 47%, and 44% for fluoxetine, testosterone, and placebo, respectively. Among completers, mood response rates were 70%, 57%, and 53%, respectively; in neither analysis were differences between treatments statistically significant. In contrast, testosterone was superior to fluoxetine and placebo for completers regarding fatigue. In intention-to-treat analysis, response rates were 39%, 56%, and 42% for fluoxetine, testosterone, and placebo, respectively, and for study completers, 41%, 63%, and 52%, respectively, (P < 0.05),\n While over 50% of patients treated with testosterone reported improved mood, this rate was not statistically superior to placebo. Thus, our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men. However, if validated in additional studies, testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression.\n Copyright 2004 Lippincott Williams and Wilkins", "Parkinson disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Depression affects up to 50% of these patients and is associated with a variety of poor outcomes for patients and their families. Despite this, there are few evidence-based data to guide clinical care.\n An NIH-funded, randomized, controlled trial of paroxetine CR, nortriptyline, and placebo in 52 patients with PD and depression. The primary outcomes were the change in the Hamilton Depression Rating Scale (HAM-D) and the percentage of depression responders at 8 weeks.\n Nortriptyline was superior to placebo for the change in HAM-D (p < 0.002); paroxetine CR was not. There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks (p < 0.079). Response rates favored nortriptyline (p = 0.024): nortriptyline 53%, paroxetine CR 11%, placebo 24%. In planned contrasts of response rates, nortriptyline was superior to paroxetine CR (p = 0.034). Nortriptyline was also superior to placebo in many of the secondary outcomes, including sleep, anxiety, and social functioning, while paroxetine CR was not. Both active drug treatments were well tolerated.\n Though relatively modest in size, this is the largest placebo-controlled trial done to date in patients with Parkinson disease (PD) and depression. Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not. When compared directly, nortriptyline produced significantly more responders than did paroxetine CR. The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors.", "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.", "In a double-blind clinical trial involving 28 patients with multiple sclerosis and major depressive disorder, 14 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy and 14 to placebo plus psychotherapy. Clinical judgments indicated that patients treated with desipramine improved significantly more than the placebo group. This was confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck Depression Inventory scores. Side effects limited desipramine dosage in half of the treated patients. The authors conclude that desipramine has a modest beneficial effect in serious depression associated with multiple sclerosis but that side effects may be more of a limiting factor than in patients without medical or neurologic disease.", "The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder (MDD) in persons with multiple sclerosis (MS).\n In this double-blind trial, 42 participants with MS and MDD were randomly assigned to one of two parallel 12-week treatment arms: paroxetine or placebo. The participants started at an initial dose of 10 mg/day paroxetine or placebo, titrated up to 40 mg daily based on symptoms response and side effects. The primary outcome measure was the Hamilton Rating Scale for Depression (HAM-D). Secondary outcomes included fatigue, anxiety and self-reported quality of life.\n Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment. Although the treatment group improved more than the control group on most measures, few differences were statistically significant. For the primary outcome, 57.1% of participants in the treatment arm had at least a 50% reduction in HAM-D score, compared with 40% in the control group (nonsignificant). Treatment effects were greater among the participants who completed the study; 78.6% of completers had a treatment response compared with 42.1% of controls (P=.073).\n Although paroxetine may not be efficacious for all persons with MS and MDD, it appears to benefit some individuals.", "To determine the response of physically ill elderly depressed patients to treatment.\n Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine.\n Response rate as defined by the 17-item Hamilton Depression Rating Scale.\n Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02).\n The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important.", "The purpose of this randomized double-blind, placebo-controlled study was to compare the efficacy and safety of fluoxetine plus group psychotherapy versus group psychotherapy alone in HIV-seropositive men (based on 1986 CDC classes II, III, and IV.C.2) who had been diagnosed with major depressive disorder (DSM-III-R).\n During a 7-week trial, patients were treated with fluoxetine 20-60 mg or placebo 1-3 capsules per day and were seen in weekly supportive group psychotherapy. In addition, subjects were rated on the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions scales for Improvement (CGI-I) and Severity of Illness (CGI-S), and the short version of the Beck Depression Inventory (BDI-13). Of the 47 patients enrolled in the study, 25 were administered fluoxetine and 22 were given placebo.\n Subjects who received fluoxetine began to show significantly more improvement than patients who received placebo on both self- and observer-rated scales by the end of the first week of treatment. By endpoint, patients treated with fluoxetine experienced greater mean changes from baseline compared with placebo-treated patients on the HAM-D-17 (12.1 vs. 6.6; F = 6.53, df = 1,45; p < .05) and BDI-13 (5.9 vs. 1.2; F = 5.73, df = 1,45; p < .05), and a greater percentage of fluoxetine-treated patients experienced a > or = 50% in HAM-D-17 scores (64% vs. 23%; chi2= 8.60, df = 1, p < .01). Differences were particularly apparent in subjects whose initial depressive episodes were rated as severe (i.e., HAM-D-17 score > or = 24). Severely depressed patients treated with fluoxetine had an endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated with placebo (F = 6.02, df = 1,11; p < .05). Further, side effects were generally mild and transient. The most frequently noted effects reported by subjects treated with fluoxetine were nausea, dry mouth, headache, and diarrhea, in decreasing order of frequency.\n This study supports the efficacy and safety of fluoxetine over and above group psychotherapy for the treatment of HIV-associated major depression.", "The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients.", "Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy.\n To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression.\n The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 x 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher.\n Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142).\n The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .017).\n Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (-2.26 points; 96.7% CI, -4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, -1.90 to 4.16; P = .37; effect size = 0.11).\n This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression.\n isrctn.org Identifier: ISRCTN15858091.", "To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited.\n In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale.\n Using the \"last observation carried forward\" (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant.\n This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression.", "Poststroke depression is a frequent condition and important to treat. The aim of this trial was to study the efficacy and tolerability of sertraline.\n In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were enrolled during the period September 1998 to January 2001 in a randomized, double-blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3-375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale. The Emotional Distress Scale (EDS) was administered and the occurrence of emotionalism and quality of life (QoL) were assessed, as well as neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week 6) and long-term (week 26).\n Of the 123 patients, 62 were treated with sertraline (50-100 mg/day) and 61 with placebo. Both groups improved substantially, with no differences between the treatments, either for major depressive episode or minor depressive disorder, or for short- or long-term antidepressant effect and neurologic outcome. EDS revealed a better outcome with sertraline at week 6 (p < .05). At week 26, the improvement in QoL was better in sertraline patients (p < .05) and there was a trend for emotionalism (p = .07). No serious side effects were seen.\n Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment. Positive effects specific to sertraline were identified in emotional distress, emotionalism, and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy.", "Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI.\n Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography.\n The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. Conclusions: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event.", "When present, depression in the context of human immunodeficiency virus (HIV) illness not only detracts from quality of remaining life but may interfere with motivation to obtain good medical care as well, thus directly influencing life's duration. This study was undertaken to assess the efficacy of fluoxetine in treating depression occurring in the context of HIV illness and to assess effects, if any, of fluoxetine on immune status (T-cell subsets).\n Patients had originally participated in a double-blind, placebo-controlled, 6-week study of imipramine. Imipramine nonresponders or relapsers and side effect dropouts were offered open treatment with fluoxetine for 12 weeks. Adjunctive dextroamphetamine was prescribed if the treating psychiatrist considered it clinically indicated. Eligibility criteria for the original study included a DSM-III-R diagnosis of major depression, dysthymia, or both. Concurrent HIV medications were permitted.\n Measures included the clinician-rated Hamilton Rating Scale for Depression and Clinical Global Impressions Scale, and patient-rated Brief Symptom Inventory and Beck Hopelessness Scale. Of the 23 patients receiving only fluoxetine, 83% (N = 19) were classified as responders. Of the 7 (30%) who also received adjunctive dextroamphetamine, all responded. Patients with CD4 cell counts under 200/cu mm did as well as others. CD4 cell count was not influenced by duration of treatment with fluoxetine; the average decline was that expected due to the passage of time alone. Side effects were mild and relatively infrequent.\n In this open treatment study, fluoxetine alone and fluoxetine plus dextroamphetamine were found to be effective treatments for patients with HIV illness and Axis I depression, regardless of the initial level of immune deficiency or number or type of HIV medications used concurrently. No negative effects on immune status were observed.", "The relative importance of direct analgesic and antidepressant effects of antidepressant drugs in rheumatoid arthritis (RA) is not clear.\n Forty-eight female out-patients with RA, with depression and/or anxiety, were entered into a double-blind, placebo-controlled study of dothiepin in doses up to 150 mg daily to assess the effects on mood [Hospital Anxiety and Depression (HAD) scale and Hamilton Rating Scale (HRS) for Depression], pain [visual analogue scale (VAS)] and disability [Health Assessment Questionnaire (HAQ)].\n Repeated measures multivariate analysis of variance revealed that treatment had a significant effect on pain (F(d.f. 1,39) =5.7, P=0.02). There were further interaction effects between treatment and time on pain (F(d. f. 3,117) =3.3, P=0.03), disability (F(d.f. 3,117)=4.2, P=0.008) and duration of early morning stiffness (F(d.f. 3,117) =3.3, P=0.03). Depression (HRS) was considerably reduced in both the dothiepin and placebo groups, and there was no significant difference between groups. Post hoc analyses using analysis of covariance revealed that, in the dothiepin group, pain was significantly reduced by week 4 and remained so at week 12. Disability scores and duration of early morning stiffness were consistently lower in the dothiepin group, although differences failed to reach statistical significance at any follow-up assessment. In the group as a whole, reductions in pain were highly significantly correlated with reductions in HAD depression (r =0.63, P<0.0005), HAD anxiety (r=0.46, P=0.001) and HRS depression (r=0.37, P=0.01).\n Dothiepin is effective in relieving pain, disability and reducing the duration of early morning stiffness in out-patients with RA. Although there is a general association between pain reduction and improved anxiety and depression, the analgesic effect of dothiepin is independent of its antidepressant effect. Individual variation is considerable and further research should try to identify mechanisms of interaction between the antidepressant and analgesic effects of treatment in different patient groups.", "Depression has a reported mean prevalence of 24% in patients diagnosed with cancer. However, little systematic research on the efficacy of antidepressants in patients with cancer has been performed.\n The efficacy and safety of mianserin were studied in 55 depressed women with breast cancer (stage I or II and without known metastases), in a randomised, double-blind, six-week, placebo-controlled study.\n Statistically significant differences in the decrease in score from baseline on the Hamilton Rating Scale for Depression and the number of responders, favouring mianserin, were present after 28 and 42 days of treatment. Significantly more placebo-treated patients prematurely terminated the study due to lack of efficacy while the safety profile of mianserin was similar to that of placebo.\n Treatment with mianserin resulted in a significant improvement in depressive symptoms in cancer patients, and was well tolerated.", "To test the safety and efficacy of fluoxetine in patients with renal failure on dialysis.\n Fourteen patients with major depression and end stage renal disease on hemodialysis were randomized into two groups for an eight-week study. Subjects as well as investigators were blinded as to which subject received fluoxetine and which placebo. Patients were carefully monitored concerning adverse events, serum fluoxetine and norfluoxetine levels, and psychological measurements of degree of depression.\n No patients discontinued treatment because of adverse events, all of which were minor. All psychological tests showed improvement in depression at the four-week and eight-weeks point, although statistical significance could only be demonstrated at the fourth week of this study. All patients in the active group had serum plasma concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight weeks, similar to levels in patients with normal renal function in a previous open label study.\n This study confirms the relative safety of fluoxetine in depressed patients in renal failure on hemodialysis. It also suggests that fluoxetine may be efficacious in depressed patients on dialysis." ]

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[ "The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study.", "Clinical and functional evaluation of the efficacy of otilonium bromide: a multicenter study in Italy.", "Clinical trial: the effect of amitriptyline in patients with diarrhoea-predominant irritable bowel syndrome.", "[Treatment of irritable bowel syndrome with peppermint oil. A double-blind study with a placebo].", "Treatment of irritable bowel syndrome with lorazepam, hyoscine butylbromide, and ispaghula husk.", "Symptom relief with amitriptyline in the irritable bowel syndrome.", "The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study.", "Oral cimetropium bromide, a new antimuscarinic drug, for long-term treatment of irritable bowel syndrome.", "Is bran efficacious in irritable bowel syndrome? A double blind placebo controlled crossover study.", "[The value of adding an antispasmodic musculotropic agent in the treatment of painful constipation in functional colopathies with bran. Double-blind study].", "Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study.", "Irritable colon and depression.", "Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride).", "Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial.", "A double-blind, randomized, placebo-controlled trial of paroxetine controlled-release in irritable bowel syndrome.", "Double blind study of ispaghula in irritable bowel syndrome.", "A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.", "A clinical trial of trimebutine (Mebutin) in spastic colon.", "Irritable bowel syndrome: assessment of psychological disturbance and its influence on the response to fibre supplementation.", "The effect of trimipramine in patients with the irritable bowel syndrome. A double-blind study.", "Effects of a high-fiber diet on symptoms of irritable bowel syndrome: a randomized clinical trial.", "Irritable bowel syndrome treatment using pinaverium bromide as a calcium channel blocker. A randomized double-blind placebo-controlled trial.", "Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial.", "Double blind trial of ispaghula/poloxamer in the Irritable Bowel Syndrome.", "[Pinaverium bromide and functional colonic disease (double-blind study].", "Double blind trial of trimebutine in the irritable bowel syndrome.", "Alverine citrate fails to relieve the symptoms of irritable bowel syndrome: results of a double-blind, randomized, placebo-controlled trial.", "Longterm treatment of irritable bowel syndrome with cimetropium bromide: a double blind placebo controlled clinical trial.", "A double-blind trial of the effect of wheat bran on symptoms of irritable bowel syndrome.", "[The treatment of irritable colon. Efficacy and tolerance of buscopan plus, buscopan, paracetamol and placebo in ambulatory patients with irritable colon].", "Prifinium bromide in the treatment of the irritable colon syndrome.", "Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders.", "Psyllium therapy in the irritable bowel syndrome. A double-blind trial.", "Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial.", "Different therapeutic regimens in irritable bowel syndrome.", "Effects of cimetropium bromide on gastrointestinal transit time in patients with irritable bowel syndrome.", "Ispaghula therapy in irritable bowel syndrome: improvement in overall well-being is related to reduction in bowel dissatisfaction.", "Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial.", "The non-effect of pirenzepine in dietary resistant irritable bowel syndrome.", "Randomised-controlled trial of a fibre supplement on the symptoms of irritable bowel syndrome.", "Comparison of the therapeutic effect of wheat bran, mebeverine and placebo in patients with the irritable bowel syndrome.", "Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents." ]

[ "Although widely prescribed, the evidence for the use of antidepressants for the treatment of irritable bowel syndrome (IBS) is limited. In this study, we hypothesized that fluoxetine (Prozac), a selective serotonin reuptake inhibitor, has visceral analgesic properties, leading to increased sensory thresholds during rectal distention and improvement of symptoms, in particular in IBS patients with visceral hypersensitivity.\n Forty non-depressed IBS patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after 6 weeks of treatment with fluoxetine 20 mg or placebo. Abdominal pain scores, individual gastrointestinal symptoms, global symptom relief, and psychologic symptoms were assessed before and after the intervention.\n At baseline, 21 of 40 patients showed hypersensitivity to rectal distention. Fluoxetine did not significantly alter the threshold for discomfort/pain relative to placebo, either in hypersensitive (19 +/- 3 vs. 22 +/- 2 mm Hg above MDP) or in normosensitive (34 +/- 2 vs. 39 +/- 4 mm Hg above MDP) IBS patients. Overall, 53% of fluoxetine-treated patients and 76% of placebo-treated patients reported significant abdominal pain scores after 6 weeks (not significant). In contrast, in hypersensitive patients only, fluoxetine significantly reduced the number of patients reporting significant abdominal pain. Gastrointestinal symptoms, global symptom relief, and psychologic symptoms were not altered.\n Fluoxetine does not change rectal sensitivity in IBS patients. Possible beneficial effects on pain perception need to be confirmed in larger trials.", "Seventy-two patients complaining of abdominal pain were studied in a double blind trial with otilonium bromide (OB) (40 mg tid or placebo). In our patients we performed, before and after the treatment, a clinical evaluation (symptom variations) and functional studies (sigmoid manometry during bowel distension). As regards clinical parameters, otilonium bromide significantly reduced abdominal pain and bloating and significantly increased (p less than 0.02) the pain threshold. However the comparison with the placebo group did not show any difference between the two groups. Sigmoid motility during distension was significantly reduced (p less than 0.05) in OB group, whereas it did not change in the placebo group. We can conclude that, in irritable bowel syndrome (IBS) patients, OB is able to improve symptoms and to reduce stimulated motor activity of the sigmoid.", "Irritable bowel syndrome is the most common disorder diagnosed by gastroenterologists. Although several randomized-controlled trials have assessed the therapeutic role of antidepressant drugs, there is insufficient evidence to support their use.\n To compare the effects of low-dose amitriptyline in the treatment of diarrhoea-predominant irritable bowel syndrome in a double-blind randomized-controlled trial.\n Fifty-four patients who fulfilled Rome II criteria for diarrhoea-predominant irritable bowel syndrome were included in this study. Organic causes were ruled out by standard laboratory and radiological tests, and rectosigmoidoscopy. Patients were randomly assigned to receive either 10 mg amitriptyline daily or placebo. Subjects were followed up for 2 months and symptoms were assessed using a questionnaire. Intention-to-treat and per-protocol analysis was performed.\n Fifty patients completed the study. At 2 months, the amitriptyline group showed greater (P < 0.05) reduction in the incidence of loose stool and feeling of incomplete defecation. Patients receiving amitriptyline showed greater complete response, defined as loss of all symptoms, compared with those receiving placebo (68% vs. 28%, P = 0.01). Adverse effects were similar between the two groups.\n Amitriptyline may be effective in the treatment of diarrhoea-predominant irritable bowel syndrome and at low dose is well tolerated.", "nan", "A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam, hyoscine butylbromide, and ispaghula husk in 12 randomised blocks of eight patients with the irritable bowel syndrome (IBS). Each of the three agents caused a sustained symptomatic improvement in some of the patients, although only with ispaghula was the difference between the real and dummy preparation statistically significant. When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial. Seven patients improved among the 12 who received potent preparations of all three agents, and between four and six patients improved in the groups receiving one or two of the potent preparations. These therapeutic results, though far from perfect, show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects. Similar combinations of other therapeutic agents may be more effective, but it will be possible to determine this only by carrying out factorial therapeutic trials.", "Anti-depressants have been reported to be useful in the management of the Irritable Bowel syndrome. We studied the efficacy of amitriptyline for 12 weeks in a randomized double-blind placebo-controlled trial. Forty patients who met predefined criteria entered the trial. They received 25 mg amitriptyline for the first week, 50 mg for the second week and 75 mg nightly thereafter until the end of the 12th week. The drug and placebo groups were comparable in all major pretreatment variables. Amitriptyline was found to be significantly more effective than placebo in producing global improvement, increasing feelings of well-being, reducing abdominal pain and increasing satisfaction with bowel movements. Younger age and increasing extroversion predicted a better response to amitriptyline. Severity of depressive and anxiety symptoms and other personality variables did not influence outcome.", "Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness.\n To compare the effects of fluoxetine and placebo in the treatment of pain and constipation-predominant irritable bowel syndrome in a double-blind randomized-controlled trial.\n Forty-four cases meeting Rome II criteria for irritable bowel syndrome with predominance of pain and constipation were included in this study. Organic causes were ruled out by detailed history, physical examination, laboratory tests and colonoscopy. Participants were then randomly assigned to receive either fluoxetine or placebo for 12 weeks. Symptoms addressed by the Rome II criteria were recorded during treatment and 4 weeks after termination of treatment.\n Fluoxetine was significantly more effective than placebo in decreasing abdominal discomfort, relieving feeling and sense of bloating, increasing frequency of bowel movements and decreasing consistency of stool. Mean number of symptoms per patient decreased from 4.6 to 0.7 in the fluoxetine group vs. 4.5 to 2.9 in controls (P < 0.001).\n Fluoxetine is an effective and well-tolerated short-term treatment for pain and constipation-predominant irritable bowel syndrome.", "Most drugs are ineffective for the long-term treatment of irritable bowel syndrome (IBS). The beneficial effects of medical treatment of IBS are poor and last for only a relative short time. Over a period of 6 months, we investigated the effectiveness of cimetropium bromide, a new antimuscarinic compound, in patients with IBS. Forty-eight patients were treated at random and in double-blind fashion with cimetropium bromide (50 mg, tid) or placebo for 6 months. Personal diary cards and monthly check-ups guaranteed the monitoring of symptoms (mainly pain). In addition, personality patterns (MHQ-CBA tests) were obtained for the patients before and after therapy, both to detect possible psychoneurotic traits and to observe the changes in these traits in relation to the changes in pain symptoms. Three patients on placebo and one on cimetropium dropped out. At the end of therapy, pain scores had decreased an average of 16% in the placebo group and 87% in the cimetropium group (p less than 0.01). Twenty patients (87%) on cimetropium versus five patients (24%) on placebo considered themselves to be globally improved (p less than 0.01). The MHQ test showed significant improvement in the anxiety score in the cimetropium group only. The CBA test confirmed a significant decrease in anxiety state (STAI-X-1) after cimetropium treatment. Eleven patients (48%) on cimetropium reported side effects (mainly dry mouth and sleepiness), but none withdrew from the study. The results of this trial indicate that long-term treatment of IBS with cimetropium bromide significantly improves symptoms and associated psychological disorders.", "Twenty eight patients with classical irritable bowel syndrome completed a double blind placebo controlled crossover trial in which they added to their normal diet a daily supplement of either 12 bran biscuits (1 = 1.3 g fibre) or 12 placebo biscuits (1 = 0.23 g fibre). Each biscuit was given for three months in random order with crossover to the alternative biscuit at three months. After the initial three months therapy, there was a significant symptomatic improvement compared with pretreatment in both the bran treated (p less than 0.01) and placebo treated groups (p less than 0.01), but there was no significant difference in symptom scores between these two groups. There was no further improvement in either group after the second three months treatment with the alternative therapy. When crossover data for all 28 subjects were combined, symptoms scores after three months bran therapy and after three months placebo therapy did not differ significantly. Twenty four patients completed three day stool collections in both treatment periods. When the symptomatic response to bran among 15 subjects in whom stool weights rose on bran was compared with that among nine subjects whose stool weights were static or fell on the bran, it was shown that symptomatic improvement was independent of an increase in stool weight. These data suggest that in irritable bowel syndrome, especially that associated with abdominal pain, the beneficial effects of bran are due to a placebo response which is independent of an increase in stool weight.", "nan", "To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria.\n Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored.\n The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups. but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01).\n Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.", "nan", "The effectiveness of Bentyl (dicyclomine hydrochloride) 40 mg 4 times daily was evaluated in an ambulatory population with recent irritable bowel syndrome (IBS). During the 2-week double-blind study, the effects of dicyclomine hydrochloride compared to placebo were assesed by: 1) physicians' global evaluation of treatment, 2) patients' self-evaluation of treatment, and 3) patients' evaluation of duration of abdominal pain. It was concluded that over a 2-week period dicyclomine hydrochloride 40 mg 4 times a day is superior to placebo in improving the overall condition of the patient, decreasing abdominal pain, decreasing abdominal tenderness, and improving bowel habits. The majority of adverse effects reported were related to the anti-cholinergic activity of the drug.", "To determine the efficacy and tolerability of an enteric-coated peppermint-oil formulation (Colpermin), we conducted a prospective, randomized, double-blind, placebo-controlled clinical study in 110 outpatients (66 men/44 women; 18-70 years of age) with symptoms of irritable bowel syndrome. Patients took one capsule (Colpermin or placebo) three to four times daily, 15-30 min before meals, for 1 month. Fifty-two patients on Colpermin and 49 on placebo completed the study. Forty-one patients on Colpermin (79%) experienced an alleviation of the severity of abdominal pain (29 were pain-free); 43 (83%) had less abdominal distension, 43 (83%) had reduced stool frequency, 38 (73%) had fewer borborygmi, and 41 (79%) less flatulence. Corresponding figures for the placebo group were: 21 patients (43%) with reduced pain (4 were pain-free), 14 (29%) with reduced distension, 16 (32%) with reduced stool frequency, 15 (31%) with fewer borborygmi, and 11 (22%) with less flatulence. Symptom improvements after Colpermin were significantly better than after placebo (P < 0.05; Mann-Whitney U-test). One patient on Colpermin experienced heartburn (because of chewing the capsules) and one developed a mild transient skin rash. There were no significant changes in liver function test results. Thus, in this trial, Colpermin was effective and well tolerated.", "Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disease that causes significant impairment in quality of life and accounts for $8 billion per year to the healthcare system and loss of productivity in the workplace.\n The authors examined the efficacy and safety of paroxetine controlled-release (paroxetine-CR) in patients with IBS.\n Seventy-two patients with IBS participated in a 12-week, double-blind, randomized, placebo-controlled study of paroxetine-CR (12.5 mg-50 mg/day). Efficacy was measured by Composite Pain Scores (primary outcome) and the Clinical Global Impression-Improvement (CGI-I) and Severity (CGI-S) ratings.\n In intent-to-treat analyses, there were no significant differences between paroxetine-CR (N=36) and placebo (N=36) on reduction in Composite Pain Scores, although the proportion of responders on CGI-I was significantly higher in the paroxetine-CR group. The treatment was well tolerated.\n The study did not demonstrate a statistically significant benefit for paroxetine-CR over placebo on the primary outcome measure, although there was improvement in secondary outcome measures. Overall, paroxetine-CR seems to have potential benefit in IBS. Studies with adequate samples may clarify the role of paroxetine-CR in IBS.", "A double blind placebo controlled trial of ispaghula husk in 80 patients with irritable bowel syndrome is reported. Global assessment judged treatment to be satisfactory in 82% of patients receiving ispaghula and 53% of the placebo group (p less than 0.02). Bowel habit was unchanged in the placebo group, while constipation significantly improved in patients taking ispaghula (p = 0.026). Transit time decreased significantly in those taking ispaghula compared with placebo (p = 0.001), especially in patients with initially high transit times. Abdominal pain and bloating improved in both groups, with no significant differences between ispaghula and placebo. Four of the eight withdrawals on ispaghula and 10 of the 15 withdrawals on placebo were because of treatment failure. Ispaghula significantly improves overall well being in patients with irritable bowel syndrome, and in those with constipation favourably affects bowel habit and transit time.", "Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS) although evidence of their efficacy is scarce.\n Twenty three non-depressed IBS patients were recruited from a tertiary care centre and included in a crossover trial comparing six weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug.\n After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double blind parallel arm study confirmed the benefit of citalopram over placebo.\n The SSRI citalopram significantly improves IBS symptoms, including abdominal pain, compared with placebo. The therapeutic effect is independent of effects on anxiety, depression, and colonic sensorimotor function.", "Twenty adult Indian patients suffering from the spastic form of irritable colon, i.e. abdominal pain and constipation, were given trimebutine (Mebutin), 2-phenyl, 2-dimethylamino-n-butyl 3, 4, 5-trimethoxybenzoate. Patients were given treatment with 200 mg trimebutine three times daily, or placebo for 4 weeks, and then crossed over. In addition, stool transit times were assessed by the single stool transit time (SST) method of Cummings. Results showed a statistical improvement in abdominal pain and constipation with both trimebutine and placebo after 4 weeks, but only with trimebutine after 8 weeks. Single stool transit time was significantly reduced after trimebutine.", "This study describes the effect of fibre supplementation on the gastrointestinal symptoms and general wellbeing of patients with constipated irritable bowel syndrome. In a single centre, double blind, placebo controlled trial of 3 months duration, a daily supplement of 4.1 g fibre produced no greater change in gastrointestinal symptoms than placebo. Pretreatment constipation was related to baseline fibre intake. Overall outcome was the same in treated and control groups; a considerable placebo response was evident. This level of fibre supplementation is not a useful treatment; improving neither constipation nor other symptoms. At the outset pain severity correlated with depression score on psychometric testing. Those who felt better at the end of the study scored significantly lower for depression at outset than those who felt no better. In irritable bowel syndrome a depressive emotional state profile is a powerful determinant of outcome, shaping the response to treatment, which includes a considerable placebo element.", "After organic disease had been excluded as far as possible by clinical examination, including laboratory tests, analysis of faeces, and X-ray examination or endoscopy of the upper and lower gastrointestinal tract, 61 patients were given either 50 mg trimipramine at bedtime or identically looking coded placebo in a prospective study for 4 weeks. The complaints were graded on an analogue scale by both the patients and the physicians. The results showed that the complaint scores were significantly reduced to about half in the placebo group. In the group treated with trimipramine a significantly greater reduction was found for the scores of vomiting, sleeplessness, depression, and for the mucus content of stools. The scores for tiredness during treatment had decreased less in the group receiving trimipramine than in the one receiving placebo. These improvements occurred already during the first week of treatment. No adverse side effect was recorded.", "We investigated the effects of dietary fiber on symptoms of irritable bowel syndrome.\n A single-blind randomized clinical trial was designed. Fifty-six subjects with irritable bowel syndrome were prospectively and randomly assigned to one of two groups: group 1 received a diet containing 10.4 g/d of fiber and group 2 received a diet containing 30.5 g/d of fiber. Patients' body weights, nutritional intakes as assessed with 3-d written food records, and symptom scores were assessed at baseline and at 3 mo.\n There were no dropouts during the study. Total energy intake and the distribution of macronutrients were not significantly different between groups. Total dietary fiber intake did not reach recommended levels in either group but was higher in group 2 than in group 1 (25.95 +/- 2.12 g/d versus 6.06 +/- 2.7 g/d, P < 0.05). Initial fiber intake did not differ significantly between groups. Pain scores, bowel scores, and general scores improved in both groups (from baseline to 3 mo), and no significant differences were detected between groups.\n A modest fiber intake in patients with irritable bowel syndrome relieved symptoms, but this therapeutic benefit of fiber may have been due to a placebo effect because the results were similar in the low-fiber group.", "Irritable bowel syndrome is one of the principal causes of days lost from work. As there has been no effective treatment up to now, sufferers turn to various doctors and try all sorts of medicines over extended periods that last for years. Thus irritable bowel syndrome has become a serious socio-economic problem that affects the family and the workplace.\n We conducted a randomized, double-blind, placebo-controlled trial among 40 consecutive irritable bowel syndrome patients (mean age: 31.4 +/- 1.8, range 17-52 year; females). Pinaverium bromide (50 mg) or placebo was taken orally t.i.d with food.\n Pinaverium bromide diminished pain duration from several hours to a few minutes (P Text:nav2]Conclusions. Pinaverium bromide is safe, and produce a significant benefit in the quality of the patients life, hence may be a valuable drug for the treatment of irritable bowel syndrome patients.", "The efficacy of antidepressants in irritable bowel syndrome (IBS) is controversial. No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor. Our aim was to determine whether imipramine and citalopram are efficacious in IBS.\n This was a randomized, double-blind, placebo-controlled, parallel group pilot trial with imipramine (50 mg) and citalopram (40 mg).\n Of 51 IBS patients randomized, baseline characteristics were comparable among the treatment arms; the majority was diarrhea-predominant. Adequate relief of IBS symptoms (primary endpoint) was similar for each treatment arm. Improvements in bowel symptom severity rating for interference (P = 0.05) and distress (P = 0.02) were greater with imipramine versus placebo, but improvements in abdominal pain were not. There was a greater improvement in depression score (P = 0.08) and in the SF-36 Mental Component Score (P = 0.07), with imipramine. Citalopram was not superior to placebo. Approximately 20% of the variance in scores was explained by treatment differences for abdominal pain, bowel symptom severity disability, depression and the mental component of the SF-36.\n Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo.", "nan", "nan", "nan", "Alverine citrate has been used in the treatment of irritable bowel syndrome for many years.\n To compare the efficacy and safety of a new formulation of alverine citrate, a 120-mg capsule, with placebo given three times daily for 12 weeks.\n One hundred and seven patients with irritable bowel syndrome were entered into this three-centre, double-blind, randomized, placebo-controlled, parallel group trial. The primary end-point was relief of abdominal pain indicated by improvement in the scores for severity and frequency. Secondary efficacy variables included scores for other clinical symptoms and for overall well-being.\n The severity and frequency of abdominal pain improved in 66% and 68% of patients treated with alverine citrate vs. 58% and 69% of the placebo group, but these differences were not significant. The mean percentage reduction in the scores for abdominal pain from baseline to the final assessment, although greater in the alverine citrate group (43.7%) compared with the placebo group (33.3%), was not statistically significant.\n Alverine citrate is no better than placebo at relieving the symptoms of irritable bowel syndrome. Future trials should be designed to take into account the high and persistent placebo response seen in this condition.", "The aim of this study was to evaluate the efficacy of cimetropium bromide, a new antimuscarinic compound, in relieving symptoms of patients with irritable bowel syndrome over a three month period. Seventy consecutive outpatients were given cimetropium (50 mg tid) or placebo according to a double blind, randomised, parallel groups design. Symptoms were evaluated initially and at monthly intervals up to the end of the study period. One patient receiving placebo withdrew because of treatment failure. Pain score decreased by 40, 66, 85% in the cimetropium group, at the end of the first, second and third months respectively, compared with 26, 32 and 52% reductions among controls (p = 0.0005). At the end of treatment there was a 86% reduction in the number of abdominal pain episodes per day in the cimetropium group compared with 50% in the placebo group (p = 0.001). Constipation and diarrhoea scores decreased by 59 and 49% in the cimetropium treated patients, compared with 37 and 39% in controls, the differences between being not significant. At the end of the study 89% of the patients treated with cimetropium considered themselves as globally improved as opposed to 69% in the placebo group (p = 0.039). The corresponding 95% confidence intervals for the differences between the proportion of improved patients in the two groups were from 11% to 29%. Six patients taking cimetropium complained of slight dry mouth. The results of this study showed that cimetropium bromide is effective in relieving pain in patients with irritable bowel syndrome.", "59 outpatients with irritable bowel syndrome participated in a randomised double-blind trial. The patients in the treatment group received three biscuits daily each containing 10 g of ordinary miller's bran, whereas the patients in the control group received wheat biscuits of a similar appearance. The treatment period was 6 weeks. 52% of the patients in the treatment group noted subjective improvement compared with 65% in the control group. The results of this trial do not support the routine use of miller's bran in irritable bowel syndrome.", "A double-blind, randomized parallel group trial comparison involving 712 patients with irritable bowel syndrome was performed. Over a treatment period of 4 weeks hyoscine-N-butylbromide (30 mg/day p.o.) plus paracetamol (1 500 mg/day p.o.), hyoscine-N-butylbromide (30 mg/day p.o.), paracetamol (1. 500 mg/day p.o.) or placebo (3 tablets/day p.o.) were administered. Patients kept a diary and entered a daily rating of their symptoms (visual analogue scale). At the end of the four weeks 81% of the patients in the Buscopan plus group were deemed \"responder\" (marked or some improvement in symptoms). In the Buscopan group 76%, in the paracetamol group 72% and in the placebo group 64% of the patients were responders. The differences between the Buscopan plus group and the placebo group, and between the Buscopan group and the placebo group were statistically significant. The daily rating on the analogue scale showed a statistically significant improvement in abdominal pain intensity in the Buscopan plus group versus the placebo group and in the Buscopan plus group versus the paracetamol group. Thirty-eight patients ( = 5%, no differences between the treatment groups) experienced adverse effects, that did not require treatment. Buscopan plus and Buscopan are suitable for the treatment of the irritable bowel syndromes.", "Eighteen patients with irritable colon syndrome were treated with a new anticholinergic drug (prifinium bromide) and with a placebo in a 6-wk, randomized, double-blind cross-over study. The drug was orally administered in a daily dose of 90 mg before meals. Three manifestations (pain, flatulence, constipation, and/or diarrhea), scored weekly, were used as assessment criteria. Mean over-all ratings showed a difference in favor of the drug, and were statistically significant. Side effects were rare and mild. We have come to the conclusion that this anticholinergic drug may be of benefit to patients with pain-predominant forms of irritable colon syndrome.", "Studies of antidepressants and psychological treatments in functional bowel disorders (FBD) are methodologically limited. The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe FBD (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD). We also evaluated the amenability of clinically meaningful subgroups to these treatments.\n This randomized, comparator-controlled, multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD. Participants received psychological (CBT vs. EDU) or antidepressant (DES vs. PLA) treatment for 12 weeks. Clinical, physiologic, and psychosocial assessments were performed before and at the end of treatment.\n The intention-to-treat analysis showed CBT as significantly more effective than EDU (P = 0.0001; responder rate, 70% CBT vs. 37% EDU; number needed to treat [NNT ], 3.1). DES did not show significant benefit over PLA in the intention-to-treat analysis (P = 0.16; responder rate, 60% DES vs. 47% PLA; NNT, 8.1) but did show a statistically significant benefit in the per-protocol analysis (P = 0.01; responder rate, 73% DES vs. 49% PLA; NNT, 5.2), especially when participants with nondetectable blood levels of DES were excluded (P = 0.002). Improvement was best gauged by satisfaction with treatment. Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms, abuse history, no depression, and diarrhea-predominant symptoms; CBT was beneficial over EDU for all subgroups except for depression.\n For female patients with moderate to severe FBD, CBT is effective and DES may be effective when taken adequately. Certain clinical subgroups are more or less amenable to these treatments.", "A randomized, double-blind trial of a psyllium preparation was initiated in 77 patients with painful irritable bowel syndrome. Sixty-patients finished and submitted symptom data for 8 weeks while taking placebo (n = 34) or psyllium (n = 26). Increase in normal stools and decrease in pain severity (p less than 0.05) occurred equally in both groups. Subjective improvement was reported by 24 of 34 patients on placebo and 20 or 26 on psyllium (p greater than 0.05). Five symptom variables were significantly correlated (p less than 0.05) with patient's subjective global assessment (R = 0.64). Discriminant analysis of Minnesota Multiphasic Personality Inventory variables yielded overall rates of correct prediction of 66.1% for whether patients got \"much better\" and 77.9% for whether they voluntarily dropped from the study. A major placebo effect occurs in patients with painful irritable bowel syndrome and is probably responsible for the efficacy of psyllium. Personality factors influence the magnitude of therapeutic response and whether patients discontinue treatment within 8 weeks.", "The purpose of the trial was to determine whether a high-fiber diet (HFD) alone or in combination with paroxetine or placebo was effective treatment for patients with irritable bowel syndrome (IBS).\n Design: Trial of HFD alone (Group 1) followed by a randomized, double-blind trial of HFD with paroxetine or placebo (Group 2). Setting: Gastroenterology office in a 524-bed university-affiliated community hospital in Pittsburgh. Patients: Men and women, aged 18-65 yr, previously diagnosed with IBS but otherwise healthy. Intervention: Institution of HFD in 98 participants consuming low- or average-fiber diets. Allocation of paroxetine to 38 and placebo to 43 symptomatic participants consuming HFDs. Measurements: Overall well-being, abdominal pain, and abdominal bloating (Groups 1 and 2); food avoidance, work functioning, and social functioning (Group 2).\n In Group 1, overall well-being improved in 26% patients, and abdominal pain and bloating decreased in 22% and 26% patients, respectively, with an HFD. In Group 2, overall well-being improved more with paroxetine than with placebo (63.3%vs 26.3%; p= 0.01), but abdominal pain, bloating, and social functioning did not. With paroxetine, food avoidance decreased (p= 0.03) and work functioning was marginally better (p= 0.08). Before unblinding, more paroxetine recipients than placebo recipients wanted to continue their study medication (84%vs 37%; p < 0.001).\n The difference in overall well-being found in our paroxetine/placebo trial is greater than that found in previously published drug/placebo trials for IBS. Moreover, the difference in well-being applied to nondepressed recipients of paroxetine.", "nan", "Cimetropium bromide is a new antimuscarinic compound with strong antispasmodic activity. The aim of this study was to evaluate the effects of oral cimetropium bromide on total gut transit time in patients with irritable bowel syndrome. Forty patients, divided according to their initial total gastrointestinal transit times and presenting symptoms, were treated with cimetropium bromide 50 mg t.d.s. or placebo for 1 month according to a double-blind, parallel group design. Before and after treatment all subjects ingested 24 radio-opaque markers. The total intestinal transit time was determined by evaluating the rate of disappearance of markers from plain X-ray films of the abdomen taken every 24 h for 4 days. Pain and bowel habits were also monitored. Seven patients did not complete the study. Cimetropium bromide significantly (P less than 0.01) shortened the whole gut transit time in patients with prolonged transit time (80.8 +/- 4.0 h before vs 60.8 +/- 6.7 h after treatment) and improved the global clinical condition significantly compared with placebo (P = 0.029). In patients with a short total intestinal transit time, cimetropium bromide had no effect on whole gut transit time and did not significantly improve symptoms. The results of this study indicate that oral cimetropium bromide is effective both objectively and subjectively in a subgroup of irritable bowel syndrome patients with constipation.", "This placebo controlled, double-blind, cross-over trial involving 20 patients was conducted to assess the effect of ispaghula husk on the major bowel symptoms and the whole gut transit time in irritable bowel syndrome (IBS) and to determine if changes in these parameters were related to global improvement. All 20 patients were interviewed at the end of the treatment periods and 14 patients kept concurrent daily records. Ispaghula therapy resulted in improvement in global symptoms and satisfying bowel movements (P less than 0.001) but produced no change in abdominal pain or flatulence. There was a correlation between the improvement of well-being and the number of days of satisfying bowel movements (P less than 0.001) but not with the indexes of pain, stool frequency or changes in the transit time. The easing of bowel dissatisfaction appears to be a major reason for the therapeutic success of ispaghula in IBS.", "The use of peppermint oil in treating the irritable bowel syndrome has been studied with variable results probably due to the presence of patients affected by small intestinal bacterial overgrowth, lactose intolerance or celiac disease that may have symptoms similar to irritable bowel syndrome.\n The aim of the study was to test the effectiveness of enteric-coated peppermint oil in patients with irritable bowel syndrome in whom small intestinal bacterial overgrowth, lactose intolerance and celiac disease were excluded.\n Fifty-seven patients with irritable bowel syndrome according to the Rome II criteria, with normal lactose and lactulose breath tests and negative antibody screening for celiac disease, were treated with peppermint oil (two enteric-coated capsules twice per day or placebo) for 4 weeks in a double blind study. The symptoms were assessed before therapy (T(0)), after the first 4 weeks of therapy (T(4)) and 4 weeks after the end of therapy (T(8)). The symptoms evaluated were: abdominal bloating, abdominal pain or discomfort, diarrhoea, constipation, feeling of incomplete evacuation, pain at defecation, passage of gas or mucus and urgency at defecation. For each symptom intensity and frequency from 0 to 4 were scored. The total irritable bowel syndrome symptoms score was also calculated as the mean value of the sum of the average of the intensity and frequency scores of each symptom.\n At T(4), 75% of the patients in the peppermint oil group showed a >50% reduction of basal (T(0)) total irritable bowel syndrome symptoms score compared with 38% in the placebo group (P<0.009). With peppermint oil at T(4) and at T(8) compared with T(0) a statistically significant reduction of the total irritable bowel syndrome symptoms score was found (T(0): 2.19+/-0.13, T(4): 1.07+/-0.10*, T(8): 1.60+/-0.10*, *P<0.01 compared with T(0), mean+/-S.E.M.), while no change was found with the placebo.\n A 4 weeks treatment with peppermint oil improves abdominal symptoms in patients with irritable bowel syndrome.", "No subjective or objective evidence of beneficial effect was observed from the use of Pirenzepine in irritable bowel syndrome (IBS) patients who had not responded to a high fibre diet.", "The aim of this study was to assess the effect of coarse wheat bran on specific bowel function parameters and symptoms in patients with irritable bowel syndrome (IBS). A longitudinal, prospective, randomised, placebo-controlled trial was undertaken. The duration of treatment was eight to 12 weeks and this consisted of 10-20 g/day of coarse wheat bran or a low fibre placebo taken in addition to the normal diet. Twenty-eight outpatients fulfilling the Rome criteria for constipation-predominant IBS were recruited to the trial (14 in the treatment group; 14 in the placebo group). Twelve people completed the trial in the treatment group and ten in the placebo group. The main outcome measures included changes in symptoms recorded in a diary, changes in objective measurements of bowel function and subjective overall feelings of improvement. The bran group significantly increased their non-starch polysaccharide (NSP) intake over that of the placebo group (p < 0.05). Mean stool wet weight increased significantly more in the bran group than in the placebo group (p < 0.05), but other bowel function measurements and all recorded symptoms were not different. Many patients reported changes in bowel habit that were not reflected in the objective measurements. The addition of coarse wheat bran to the diet increased NSP ingestion and stool wet weight in this group of IBS patients, but no evidence was obtained that such treatment was of benefit to these patients, other than a placebo effect on symptoms.", "There is no generally accepted treatment in the irritable bowel syndrome (IBS), probably because of a lack of convincing therapeutic trials. In the present study, 120 outpatients with IBS participated in a prospective randomized therapeutic trial. According to a double-blind design, 40 patients received 400 mg/day mebeverine and 40 patients received a placebo. In an open branch of the trial, 40 patients were treated with 15 g/day wheat bran. The effects of treatment on symptoms were noted after 4, 8, 12 and 16 weeks of therapy. A significantly superior symptomatic effect of bran in comparison to mebeverine and placebo was demonstrated after 12 weeks, but could not be confirmed at the end of the study. There was no significant difference between the symptomatic effect of mebeverine and placebo. The compliance with the therapy was about 80% for 4 weeks, but dropped to about 50% at the end of the trial. This points to a particular difficulty in the management of patients with IBS. The results of this trial suggest that bran and mebeverine are no ideal therapy for patients with IBS but they support the therapeutic use of bran in patients with IBS.", "To determine the efficacy of amitriptyline (AMI) in treating irritable bowel syndrome (IBS) in adolescents.\n Adolescents 12 to 18 years with newly diagnosed IBS were surveyed with a symptom checklist, pain rating scale, visual analog scale, and IBS quality of life (QOL) questionnaire. Subjects were randomized in a double-blinded fashion to receive AMI or placebo, and again completed surveys at 2, 6, 10, and 13 weeks.\n Thirty-three patients (24 female) were enrolled. Patients receiving AMI were more likely to experience improvement from baseline in overall QOL at 6, 10, and 13 weeks (P = .019, .004, and .013). Patients receiving AMI were also more likely to experience a reduction in IBS-associated diarrhea at 6 and 10 weeks (P = .029 for both), a reduction in periumbilical pain at 10 weeks (P = .018), and a reduction in right lower quadrant pain at 6, 10, and 13 weeks (P = .014, .039, and .004).\n AMI significantly improves overall QOL in adolescents with IBS and should be a therapeutic option for adolescents with this disorder." ]

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[ "Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population.", "Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population.", "Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia.", "Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.", "The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements.", "[The prevention of primary liver cancer by selenium in high risk populations].", "Re: Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy.", "The effect of folic acid on the development of stomach and other gastrointestinal cancers.", "Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up.", "Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong.", "A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study.", "A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.", "No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China.", "Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.", "Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.", "Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial.", "An intervention study to prevent gastric cancer by micro-selenium and large dose of allitridum.", "The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals.", "Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions." ]

[ "Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients.\n We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian.\n Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances.\n A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality.\n The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population.\n The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements.", "Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins.\n A randomized, double-blind chemoprevention trial was conducted among 1980 subjects in Tachira State, Venezuela (whose population is at high risk for gastric cancer), to determine the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of precancerous gastric lesions. Subjects were randomly assigned to receive either a combination of vitamin C (750 mg/day), vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years. Changes in the gastric mucosa were determined by histologic diagnosis based on five biopsies taken from prespecified areas of the stomach at baseline and annually for 3 years. All biopsies were reviewed by a single expert pathologist. Progression rates (and regression rates) were calculated by comparing the first and last available gastroscopies for each subject and dividing the number of subjects whose diagnoses increased (decreased) in severity by the total follow-up time. Overall rate ratios were calculated by Poisson regression, controlling for baseline diagnosis. All statistical tests were two-sided.\n Median plasma vitamin levels were increased in the treatment group between baseline and 1 year after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69) to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from 47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for vitamin C. Overall progression rates per 100 person-years were 74.3 in the placebo group and 67.8 in the group randomly assigned to vitamins. Overall regression rates were 109.4 in the placebo group and 116.5 in the group randomly assigned to vitamins. There was no statistically significant difference in progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15) or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and placebo groups.\n Supplementation with antioxidant micronutrients is not an effective tool for gastric cancer control in this high-risk population. The results of this trial are consistent with previous findings on the lack of effect of nutritional supplementation on precancerous gastric lesions.", "A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia.\n To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian.\n Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years.\n A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups.\n No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus.\n Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia.", "To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.\n A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.\n Seven dermatology clinics in the eastern United States.\n A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years.\n Oral administration of 200 microg of selenium per day or placebo.\n The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers.\n After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred.\n Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made", "The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group.\n After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided.\n With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males.\n The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.", "To study the preventive effects of selenium on primary liver cancer.\n After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day.\n During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01).\n The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible.", "nan", "To evaluate the roles of folic acid and beta-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers.\n In a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups: (1) folate (FA, 20 mg per day plus vitamin B(12) 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); (2) natural beta-carotene (N-betaC, 30 mg per day for first year, then 30 mg two times a week for the next); (3) synthetic beta-carotene (S-betaC, administered as in N-betaC); and (4) placebo. Follow-ups continued from 1994 to 2001.\n A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-betaC and S-betaC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P = 0.04). A similar trend was observed in both N-betaC and S-betaC groups (P = 0.07 - 0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P = 0.004, vs placebo), and a lower risk for GI cancers (OR = 0.12; 95% confidence interval, 0.03 - 0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P = 0.04), reversed intestinal metaplasia (P = 0.06) at the end of follow-up, and reversed displasia (P = 0.017) at 12 months. Two cases of false jaundice were found in beta-carotene groups with no influence on administration, and no side-effects were reported in FA group.\n This trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of beta-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.", "In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.\n To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality.\n Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.\n Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.\n Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.\n The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.", "High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect.", "Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD.\n The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005.\n A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03).\n There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.", "The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.", "A randomised double-blind intervention trial was carried out in Huixian, Henan Province, People's Republic of China, to determine whether combined treatment with retinol, riboflavine, and zinc could lower the prevalence of precancerous lesions of the oesophagus. 610 subjects in the age group 35-64 were randomised to receive once a week the active treatment (15 mg [50 000 IU] retinol, 200 mg riboflavine, and 50 mg zinc) or placebo. Both at entry to the study and at the end of the treatment, 13.5 months later, the subjects were examined, with an emphasis on signs of vitamin A and riboflavine deficiences, and riboflavine, retinol, beta-carotene, and zinc levels were measured. Compliance was excellent. The final examination, on 567 (93%) subjects, included oesophagoscopy and at least two biopsies. The intervention did not affect the prevalence of oesophageal lesions: after one year, the prevalence of oesophagitis with or without atrophy or dysplasia was 45.3% in the placebo group and 48.9% in the vitamin/zinc treated group.", "Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration.\n To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events.\n A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years.\n Daily dose of natural source vitamin E (400 IU) or matching placebo.\n Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations.\n Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure.\n In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.", "Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation.\n In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene.\n Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points.\n In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.", "Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons.\n To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women.\n In the Women's Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years.\n Administration of 600 IU of natural-source vitamin E on alternate days.\n Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer.\n During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53).\n The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.", "People have more and more concerned about allitridum as studies have shown that taking more raw garlic associated with a lower risk for cancers of the alimentary system. In the present study, we tried to examine whether a large dose of allitridum and a microdose of selenium prevent gastric cancer.\n A double-blind intervention study was performed on the participants aged (35 - 74) years, who had matched at least one of the following criteria: (1) a medical history of stomach disorder, (2) a family history of tumour, or (3) smoking and/or alcohol consumption. A total of 2,526 and 2,507 persons were randomly enrolled into intervention group and control group respectively from 288 natural villages of seven communities in Qixia County, Shandong Province, China. Each person of the intervention group orally took 200 mg synthetic allitridum every day and 100 microg selenium every other day for one month of each year during November 1989 to December 1991. At the same time, people in control group were given 2 placebo capsules containing corn oid with the identical appearance to that in the intervention group.\n For all subjects the large dose of allitridum was accepted and no harmful side effects were found during the study. In the first follow-up five years (1992 - 1997) after stopping the intervention, the morbidity rates of malignant tumours in the intervention group declined by 22%, in contrast to the control group, declined by 47.3%. After adjusting for age, gender, and other potential confounders, relative risks (RRs) for all tumours and gastric cancer of the whole population were 0.67 (95% CL: 0.43 - 1.03) and 0.48 (95% CL: 0.21 - 1.06), respectively, and for male group they were 0.51 (95% CL: 0.30 - 0.85) and 0.36 (95% CL: 0.14 - 0.92), respectively. No signigicantly protective effect was found for the female subgroup.\n The present study proves that large doses of allitridum and microdorse of selenium may effectively prevent gastric cancer, especially in men.", "It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population.\n The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years.\n No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction).\n After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.", "Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions.\n Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided.\n H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements.\n H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence." ]

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[ "Message framing and sunscreen use: gain-framed messages motivate beach-goers.", "The language of uncertainty in genetic risk communication: framing and verbal versus numerical information.", "The effect of how outcomes are framed on decisions about whether to take antihypertensive medication: a randomized trial.", "Attribute Framing and Goal Framing Effects in Health Decisions.", "The effect of message frames and CVD risk factors on behavioral outcomes.", "Framing of nutrition education messages in persuading consumers of the advantages of a healthy diet.", "Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.", "Using message framing to motivate HIV testing among low-income, ethnic minority women.", "The effects of message framing and feelings of susceptibility to breast cancer on reported frequency of breast self-examination.", "Strengthening the persuasive impact of fear appeals: the role of action framing.", "Dispositional motivations and message framing: a test of the congruency hypothesis in college students.", "The impact of mailing psychoeducational materials to women with abnormal mammograms.", "The effects of message framing and ethnic targeting on mammography use among low-income women.", "Effects of framing on teratogenic risk perception in pregnant women.", "The effects of framing and action instructions on whether older adults obtain flu shots.", "Framing of outcome and probability of recurrence: breast cancer patients' choice of adjuvant chemotherapy (ACT) in hypothetical patient scenarios.", "Intentions to use hormonal male contraception: the role of message framing, attitudes and stress appraisals.", "Positive versus negative framing of a hypothetical infant immunization: the influence of involvement.", "A randomized trial of three videos that differ in the framing of information about mammography in women 40 to 49 years old.", "Cancer patients' decision making and trial-entry preferences: the effects of \"framing\" information about short-term toxicity and long-term survival.", "Message framing and pap test utilization among women attending a community health clinic.", "Message framing, dispositional optimism, and follow-up for abnormal Papanicolaou tests.", "Message framing and mammography screening: a theory-driven intervention.", "The effects of message framing on mammography utilization." ]

[ "Prospect theory suggests that people respond differentially to factually equivalent messages depending on how these messages are framed (A. Tversky & D. Kahneman, 1981). A. J. Rothman and P. Salovey (1997) relied on prospect theory to predict that messages highlighting potential \"gains\" should promote prevention behaviors such as sunscreen use best. This experiment compared the effectiveness of 4 differently framed messages (2 highlighting gains, 2 highlighting losses) to persuade 217 beach-goers to obtain and use sunscreen. Attitudes and intentions were measured before and immediately following the delivery of the framed information, and after completing the questionnaire participants were given a coupon redeemable for a small bottle of sunscreen later that same day. People who read either of the 2 gain-framed brochures, compared with those who read either of the 2 loss-framed brochures, were significantly more likely to (a) request sunscreen, (b) intend to repeatedly apply sunscreen while at the beach, and (c) intend to use sunscreen with a sun protection factor of 15 or higher.", "Within a group of 300 medical students, two characteristics of risk communication in the context of a decision regarding prenatal diagnosis for cystic fibrosis are manipulated: verbal versus numerical probabilities and the negative versus positive framing of the problem (having a child with versus without cystic fibrosis). Independently of the manipulations, most students were in favor of prenatal diagnosis. The effect of framing was only significant in the conditions with verbal information: negative framing produced a stronger choice in favor of prenatal diagnosis than positive framing. The framing effect in the verbal conditions and its absence in the numerical conditions are explained by the dominance of the problem-occurrence orientation in health matters as well as a recoding process which is more likely to occur in the numerical (the probability \"1-P\" switches to its counterpart \"P\") than in the verbal conditions. The implications for the practice of genetic counseling are discussed.", "We conducted an Internet-based randomized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease (CVD) for people with newly diagnosed hypertension to determine which framing presentation resulted in choices most consistent with participants' values.\n In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company, adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales (VAS). Participants viewed information (or no information) to which they were randomized and decided whether or not to take medication. We compared positive framing over 10 years (the number escaping CVD per 1000); negative framing over 10 years (the number that will have CVD) and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors. Finally, all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again. We calculated a relative importance score (RIS) by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction. We used logistic regression to determine the association between participants' RIS and their choice. 1,528 participants completed the study. The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values (RIS) increased as the RIS increased. Positively framed information lead to decisions most consistent with those made by everyone for the second, more fully informed decision. There was a statistically significant decrease in deciding to take antihypertensives on the second decision, both within groups and overall.\n For decisions about taking antihypertensive medication for people with a relatively low baseline risk of CVD (70 per 1000 over 10 years), both positive and negative framing resulted in significantly more people deciding to take medication compared to what participants decided after being shown all three of the presentations.\n International Standard Randomised Controlled Trial Number Register ISRCTN 33771631.", "Levin, Schneider, and Gaeth (LSG, 1998) have distinguished among three types of framing-risky choice, attribute, and goal framing-to reconcile conflicting findings in the literature. In the research reported here, we focus on attribute and goal framing. LSG propose that positive frames should be more effective than negative frames in the context of attribute framing, and negative frames should be more effective than positive frames in the context of goal framing. We test this framework by manipulating frame valence (positive vs negative) and frame type (attribute vs goal) in a unified context with common procedures. We also argue that the nature of effects in a goal-framing context may depend on the extent to which the research topic has \"intrinsic self-relevance\" to the population. In the context of medical decision making, we operationalize low intrinsic self-relevance by using student subjects and high intrinsic self-relevance by using patients. As expected, we find complete support for the LSG framework under low intrinsic self-relevance and modified support for the LSG framework under high intrinsic self-relevance. Overall, our research appears to confirm and extend the LSG framework. Copyright 2001 Academic Press.", "To examine the interactive effects of message frames and CVD risk factors on women's knowledge, beliefs, efficacy, and behavioral intentions.\n In a randomized experiment, women (n = 395) read either a loss- or gain-framed heart disease prevention message to test differential effects by risk factor status.\n Messages significantly increased knowledge, self-efficacy and intervention efficacy beliefs, and behavioral intentions. Frames had significantly different effects on self-efficacy and behavioral intent to engage in detection behaviors by parental risk factor status.\n Further study is warranted to assess effects of frames on behavioral outcomes among women at elevated CVD risk.", "Educational dietary messages can stress either the positive consequences of performing a recommended dietary behaviour (positive frame) or the negative consequences of not performing a recommended dietary behaviour (negative frame). From studies on other health behaviours, there is evidence that positive frames have a stronger impact in encouraging preventive behaviours than negative frames. The main hypothesis of the present study was therefore that positively framed messages on eating a low-fat diet and eating enough fruit and vegetables (F & V) are more persuasive than negatively framed messages.\n In a 2 (Frame: positive vs. negative) x 2 (Dietary behaviour: fat vs. F & V) design, 152 adult respondents randomly received one of four messages. Subsequently, they completed a questionnaire measuring cognitive attitude, affective attitude and intention to change the dietary behaviours.\n No significant differences in attitudes and intentions were found between the positive frame conditions and the negative frame conditions.\n Based on the current study no advice can be given yet to dietitians and other nutrition educators about whether they should emphasize the positive consequences of a dietary change or the negative consequences of not making the dietary change.", "To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects.\n 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism.\n Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05).\n In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.", "This study compared the effectiveness of 4 videotaped educational programs designed to motivate HIV testing among low-income, ethnic minority women. Four hundred eighty women were assigned randomly to watch one of 2 gain-framed or 2 loss-framed videos. Consistent with prospect theory, participants' perceptions of the certainty of the outcome of an HIV test moderated the effects of framing on self-reported testing behavior 6 months after video exposure. Among participants who reported being certain of the test's outcome, those who saw a gain-framed video reported a higher rate of testing than those who saw a loss-framed message. Among women who perceived the outcome of HIV testing as relatively uncertain, gain- and loss-framed videos led to similar rates of self-reported testing, with some advantage for the loss-framed message.", "One of two types of pamphlets on breast self-examination (BSE) attitudes and behavior was administered to subjects who were classified as high or low in feelings of susceptibility to breast cancer. Half of the subjects received pamphlets stressing the positive consequences of doing BSE and the other half received pamphlets stressing the negative consequences of not doing BSE. A previous study found negatively framed pamphlets to be superior in BSE promotion and these results were explained in terms of Tversky and Kahneman's framing postulate. The original framing postulate includes characteristics of the decision-maker as well as the type of frame presented, thus, we hypothesized an interaction between pamphlet type and level of susceptibility with the largest effect on the group with low perceived susceptibility who received negatively framed pamphlets. The hypothesized interaction did not occur, nor was there a significant effect for pamphlet type. However, there were significant differences between the BSE performance at follow-up of women who were high or low in perceived susceptibility prior to the intervention. These results are discussed in terms of implications for BSE training in the future, more specifically-the need to consider perceived level of susceptibility as an important subject characteristic that could have a large impact on the effectiveness of training programs.", "nan", "The authors examined the congruency hypothesis that health messages framed to be concordant with dispositional motivations will be most effective in promoting health behaviors. Undergraduate students (N=63) completed a measure of approach/avoidance orientation (behavioral activation/inhibition system) and read a gain- or loss-framed message promoting flossing. Results support the congruency hypothesis: When given a loss-framed message, avoidance-oriented people reported flossing more than approach-oriented people, and when given a gain-framed message, approach-oriented people reported flossing more than avoidance-oriented people. Discussion centers on implications for health interventions and the route by which dispositional motivations affect health behaviors through message framing.\n ((c) 2004 APA, all rights reserved)", "A randomized trial was conducted to evaluate the impact of mailed psychoeducational materials on adherence to subsequent annual mammography among women with prior abnormal mammograms. The results showed a 13% increment in adherence among women who received this intervention. This effect was independent of all sociodemographic and medical variables examined. We conclude that mailed psychoeducational materials may be an effective mechanism to improve adherence among women with abnormal mammogram results.", "The authors examined the effects that differently framed and targeted health messages have on persuading low-income women to obtain screening mammograms. The authors recruited 752 women over 40 years of age from community health clinics and public housing developments and assigned the women randomly to view videos that were either gain or loss framed and either targeted specifically to their ethnic groups or multicultural. Loss-framed, multicultural messages were most persuasive. The advantage of loss-framed, multicultural messages was especially apparent for Anglo women and Latinas but not for African American women. These effects were stronger after 6 months than after 12 months.", "nan", "The authors tested the effects of cues to action--messages intended to increase flu immunizations. North Dakota counties were randomly assigned to reminder letters, action letters, or no letters. Within the reminder-letter counties, Medicare recipients received either (a) a reminder from the state peer review organization (PRO) to obtain a flu shot or (b) a reminder from the PRO, framed either in terms of the loss associated with failing to get a shot or (c) the benefits associated with getting a shot. Within the action-letter counties, Medicare recipients leaned where and when to receive a flu shot. Reminder type failed to differentially affect the immunization rate (overall M = 24.5%). However, the action messages worked better (28.2%) than no message (19.6%).", "To examine the effects of framing of outcome and probabilities of cancer occurrence on the treatment preference which breast cancer patients indicate for hypothetical patient scenarios.\n A modified version of the Decision Board Instrument (Levine et al. 1992) was administered to 35 breast cancer patients with past ACT experience. Patients expressed their choice regarding ACT for six scenarios which were characterized by either negative or positive framing of outcome and by one of the three levels of probability of recurrence (high, medium, low).\n The framing had no influence on ACT choices over all three probability levels. The majority chose ACT for high and medium risk and one third switched from ACT to No ACT in the low-risk condition. This switch was statistically significant.\n Hypothetical treatment decisions against ACT occur only when the probability of recurrence is low and the benefit of ACT is small. This finding for patients with past experience of ACT is similar to those reported for other oncological patient groups still in treatment.", "Two studies are reported. Study one (N = 104) explored the extent to which male hormonal contraception is perceived as risky compared to other prevention behaviours. Study two examined the effects of message framing on intentions to use hormonal male contraception and investigated whether attitude moderates message framing effects. Three hundred and four participants read either a loss frame or gain frame message and then completed questionnaires assessing their intentions to use hormonal male contraception, stress appraisals and the theory of planned behaviour (TPB) variables. Exposure to a loss frame influenced intention to use the daily male pill in men with a more positive attitude. This suggests that attitude, but not other TPB variables or stress appraisals have the capacity to moderate framing effects. Stress appraisals, in addition to TPB variables, significantly predicted variance in behavioural intentions in men and women. These findings are discussed within the context of Prospect Theory, perceived risk and prevention/detection behaviours.", "Framing studies dealing with health messages show mixed results, although a tendency in favor of negative framing. Involvement has been hypothesized to account for these conflicting results. The authors selected a realistic issue (immunization of infants) deemed high or low involving depending on the respondent's circumstances: women with an infant or who were pregnant or intending to get pregnant in the next 12 months were deemed to be high involved; women in none of these categories were deemed to be low involved. A convenience sample of adult women was presented with a hypothetical \"new\" immunization that protected infants against respiratory complaints such as bronchitis and pneumonia Side effects (the common flu) were framed positively (90% chance of no side effects) or negatively (10% chance of side effects). The authors found positive framing to be superior for low-involved respondents, but there was no framing effect for high-involved respondents.", "To assess the effect of providing structured information about the benefits and harms of mammography in differing frames on women's perceptions of screening.\n Randomized control trial.\n General internal medicine academic practice.\n One hundred seventy-nine women aged 35 through 49.\n Women received 1 of 3 5-minute videos about the benefits and harms of screening mammography in women aged 40 to 49. These videos differed only in the way the probabilities of potential outcomes were framed (positive, neutral, or negative).\n We measured the change in accurate responses to questions about potential benefits and harms of mammography, and the change in the proportion of participants who perceived that the benefits of mammography were more important than the harms. Before seeing the videos, women's knowledge about the benefits and harms of mammography was inaccurate (82% responded incorrectly to all 3 knowledge questions). After seeing the videos, the proportion that answered correctly increased by 52%, 43%, and 30% for the 3 knowledge questions, respectively, but there were no differences between video frames. At baseline, most women thought the benefits of mammography outweighed the harms (79% positive frame, 80% neutral frame, and 85% negative frame). After the videos, these proportions were similar among the 3 groups (84%, 81%, 83%, P =.93).\n Women improved the accuracy of their responses to questions about the benefits and harms of mammography after seeing the videos, but this change was not affected by the framing of information. Women strongly perceived that the benefits of mammography outweighed the harms, and providing accurate information had no effect on these perceptions, regardless of how it was framed.", "The study purpose was to determine whether the framing of treatment information influenced patients' reported preferences for participating in treatment decision making and for trial entry. Ninety cancer patients read either neutrally-, positively-, or negatively-framed information about a chemotherapeutic treatment, then indicated their preferences for participating in the treatment decision, and whether they would participate in a clinical trial incorporating this protocol. There was no difference across information groups in preferences for participating in treatment decision making or willingness to enter such a clinical trial. Preference for participation in treatment decision making was significantly related to age (t = 2.54; p = 0.022), sex (x2 = 3.89; p = 0.05), and education (t = 2.54; p = 0.018); trial entry preferences were unrelated to these demographic variables. These results imply that, in this clinical context, attitudes towards participation in treatment decision making may be associated with characteristics of the patient, and attitudes towards trial entry may be dependent upon the clinical characteristics of a particular trial, but neither set of attitudes is influenced by the framing of protocol information.", "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.", "The effects of alternatively framed messages and dispositional optimism on follow-up for abnormal Papanicolaou tests were studied. Participants (N = 116) had a mean age of 24; 94% were black, 67% had a high school education, and 82% received public assistance. A message about losses without follow-up or gains with follow-up was randomly given. Optimism was measured with the Life Orientation Test and attendance was defined as coming or not coming within 6 weeks of contact. Logistic regressions of attendance on framing and optimism did not reveal significant relationships. Exploratory analyses revealed that personal and familial history of disease were related to attendance. Explanations for the findings and implications for research are delineated.", "Although the rising incidence of breast cancer has prompted a surge of intervention strategies aimed at increasing women's use of mammography screening, the majority of patient-directed interventions have not been driven by relevant theoretical work on persuasive health communication. The authors evaluated an intervention derived from prospect theory that was designed to increase women's adherence to recommendations for annual mammography screening. They sent 1 of 3 reminder letters (positive frame, negative frame, or standard hospital prompt) to 929 randomly selected women who were due for mammography screening and had been identified as having either a positive or negative family history of breast cancer. The primary hypothesis that women with a positive history would be more responsive to negatively framed messages, whereas women with a negative history would be more responsive to positively framed letters, was not confirmed. The lack of support for predictions derived from prospect theory raises important questions about the generalizability of laboratory research to natural settings.", "This experiment compared the effectiveness of gain-versus loss-framed messages to persuade women to obtain mammography screening. One hundred and thirty-three women 40 years and older and not adhering to current guidelines for obtaining mammography screening were assigned randomly to view either gain-framed (emphasizing the benefits of obtaining mammography) or loss-framed (emphasizing the risks of not obtaining mammography) persuasive videos that were factually equivalent. Attitudes and beliefs were measured before and immediately following the intervention. Mammography utilization was assessed 6 and 12 months later. Consistent with predictions based on prospect theory, women who viewed the loss-framed message were more likely to have obtained a mammogram within 12 months of the intervention. These findings suggest that loss-framed messages may have an advantage in the promotion of detection behaviors such as mammography." ]

[ "8150098", "17264174", "19204602", "18728175", "19494176", "15302293" ]

[ "Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women.", "Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome.", "Effects of exercise on lipoprotein particles in women with polycystic ovary syndrome.", "The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials.", "Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome.", "A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study." ]

[ "To determine whether weight loss in obese, hyperandrogenic, anovulatory women is associated with resumption of ovulation and/or with changes in insulin, androgen, and gonadotropin concentrations.\n Prospective, randomized, controlled study.\n University research center.\n Twelve obese, hyperandrogenic, anovulatory women.\n Twelve-week weight loss program in treatment (n = 6); 12-week \"waiting list\" in control group (n = 6).\n [1] Ovulation; [2] fasting insulin and glucose measurements; [3] sex hormone-binding globulin (SHBG), total and non-SHBG T concentrations; [4] LH pulse frequency, amplitude, and concentration; and [5] FSH concentration.\n In contrast with the control group who showed no change in weight, ovulation status, or hormone levels, women in the treatment group lost an average of 16.2 kg and showed a significant increase in SHBG, a significant decline in non-SHBG T, and a decline (though nonsignificant) in fasting insulin. Four of six subjects resumed ovulation. However, no changes were evident in LH pulse frequency or amplitude or in mean LH and FSH concentrations.\n Weight loss in obese, hyperandrogenic, anovulatory women appears to reduce insulin and non-SHBG T concentrations despite the absence of a change in gonadotropin secretion and may lead to resumption of ovulation.", "Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women. No data regarding the effects of a structured exercise training (ET) program on cardiopulmonary functional capacity in PCOS women are available.\n Our objective was to evaluate the effects of a 3-month ET program on cardiopulmonary functional capacity in young PCOS women.\n A prospective baseline-randomized clinical study was conducted at the University \"Federico II\" of Naples, School of Medicine (Italy).\n Ninety young overweight PCOS women were enrolled.\n Ninety young PCOS women were randomly subdivided into two groups, each composed of 45 subjects. The PCOS-T (trained) group underwent a 3-month structured ET program, whereas the PCOS-UnT (untrained) group did not. Hormonal and metabolic profiles and cardiopulmonary and exercise parameters were evaluated.\n After 3-month ET, PCOS-T showed a significant improvement in peak oxygen consumption (+35.4%; P<0.001) and in maximal workload (+37.2%; P<0.001). In PCOS-T we also observed a significant reduction in body mass index (-4.5%; P<0.001) and in C-reactive protein (-10%; P<0.001), and a significant (P<0.001) improvement in insulin sensitivity indexes. After 3 months, no changes were observed in PCOS-UnT.\n A 3-month structured ET program improves cardiopulmonary functional capacity in young PCOS women.", "Women with polycystic ovary syndrome (PCOS) commonly have insulin resistance. Insulin resistance is associated with marked abnormalities of lipoprotein size and subclass particle concentration. The purpose of this study was to examine the effects of a moderate-intensity exercise program without weight loss on lipoprotein profiles in women with PCOS.\n Thirty-seven sedentary PCOS women were randomized to either an 8- to 12-wk ramp-up followed by a 12-wk moderate-intensity exercise program (16-24 wk total, approximately 228 min x wk at 40-60% peak V x O2, n = 21) or control (no change in lifestyle, n = 16). PCOS was defined as <or=8 menses per year and hyperandrogenism (biochemical or clinical with Ferriman-Gallwey score >or=8). Fasting lipoprotein profiles were obtained before and after the intervention. Nuclear magnetic resonance spectroscopy was used to quantify the following: average particle size, total and subclass concentrations of HDL, LDL, and VLDL particles, and calculated HDL cholesterol, triglycerides, and VLDL triglycerides. Wilcoxon exact rank sums tests were used to compare changes in these parameters in the exercise group relative to controls.\n Twenty women (8 exercisers, 12 controls) completed the study. Comparing exercisers to controls, significant changes were seen in concentrations of the following lipoprotein parameters that are associated with decreased insulin resistance: decreased large VLDL (P = 0.007), calculated triglycerides (P = 0.003), VLDL triglycerides (P = 0.003), and medium/small HDL (P = 0.031) and increased large HDL (P = 0.002) and average HDL size (P = 0.001).\n In this trial, moderate-intensity exercise without significant weight loss improved several components of the lipoprotein profiles of women with PCOS. These findings support the beneficial role of moderate exercise in this high-risk population.", "Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear.\n We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS.\n Two small, randomized, placebo-controlled clinical trials were performed.\n A total of 79 obese adolescent women with PCOS participated.\n In the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo.\n Serum concentrations of androgens and lipids were measured.\n Lifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%).\n In these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction.", "We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity (MSNA). Animal studies support the concept that low-frequency electroacupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. In a randomized controlled trial, 20 women with PCOS were randomly allocated to one of three groups: low-frequency EA (n = 9), physical exercise (n = 5), or untreated control (n = 6) during 16 wk. Direct recordings of multiunit efferent postganglionic MSNA in a muscle fascicle of the peroneal nerve before and following 16 wk of treatment. Biometric, hemodynamic, endocrine, and metabolic parameters were measured. Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared with the untreated control group. The low-frequency EA group reduced sagittal diameter (P = 0.001), while the physical exercise group reduced body weight (P = 0.004) and body mass index (P = 0.004) compared with the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for body mass index and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine, and metabolic variables. For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.", "To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS).\n Prospective, randomized, placebo-controlled pilot trial.\n Academic medical center.\n Thirty-eight overweight or obese women with PCOS.\n All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone.\n Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index.\n It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg(2). Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2).\n Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS." ]

[ "10711915", "17586783", "12777339", "12091260", "9892449", "18615497", "8435687" ]

[ "Executive dysfunction and long-term outcomes of geriatric depression.", "Escitalopram prevents relapse in older patients with major depressive disorder.", "Older community residents with depression: long-term treatment with sertraline. Randomised, double-blind, placebo-controlled study.", "Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy.", "Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years.", "A pilot randomised controlled trial of a brief cognitive behavioural group intervention to reduce recurrence rates in late life depression.", "How long should the elderly take antidepressants? A double-blind placebo-controlled study of continuation/prophylaxis therapy with dothiepin. Old Age Depression Interest Group." ]

[ "This study investigated the relationship of executive and memory impairment to relapse, recurrence, and course of residual depressive symptoms and signs after remission of geriatric major depression.\n Fifty-eight elderly subjects remitted from major depression received continuation nortriptyline treatment (plasma levels 60-150 ng/mL) for 16 weeks and then were randomly assigned to either nortriptyline maintenance therapy or placebo for up to 2 years. Diagnosis was made using the Research Diagnostic Criteria and the DSM-IV criteria after an interview using the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction and memory were assessed with the Dementia Rating Scale, disability and social support were rated with the Philadelphia Multiphasic Instrument, and medical burden was assessed with the Cumulative Illness Rating Scale.\n Abnormal initiation and perseveration scores, but not memory impairment, were associated with relapse and recurrence of geriatric depression and with fluctuations of depressive symptoms in the whole group and in subjects who never met criteria for relapse or recurrence during the follow-up period. Memory impairment, disability, medical burden, social support, and history of previous episodes did not significantly influence the outcome of depression in this sample.\n Executive dysfunction was found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. These observations, if confirmed, will aid clinicians in identifying patients in need of vigilant follow-up. The findings of this study provide the rationale for investigation of the role of specific prefrontal pathways in predisposing or perpetuating depressive syndromes or symptoms in elderly patients.", "The present study investigated the efficacy and tolerability of escitalopram in the prevention of relapse of major depressive disorder (MDD) in older patients who had responded to acute treatment with escitalopram.\n A total of 405 patients who were aged 65 years or older with a primary diagnosis of MDD (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) and a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 22 or more received 12-week, open-label escitalopram 10 or 20 mg per day treatment. Remitters (MADRS </=12) were randomized to 24-week double-blind treatment with escitalopram or placebo. The primary efficacy parameter was the time to relapse, defined as either an increase in MADRS total score to 22 or more or lack of efficacy as judged by the investigator.\n Three hundred five patients achieved remission and were randomly assigned to treatment with escitalopram (N = 152) or placebo (N = 153). The primary analysis showed a clear beneficial effect of escitalopram relative to placebo on the time to relapse (log-rank test, chi(2) = 27.6, df = 1, p <0.001). The risk of relapse was 4.4 times higher for placebo- than for escitalopram-treated patients (chi(2) test, chi(2) = 22.9, df = 1, p <0.001). Significantly fewer escitalopram-treated patients relapsed (9%) compared with placebo (33%) (chi(2) test, chi(2) = 27.1, df = 1, p <0.001). Escitalopram was well tolerated with 53 patients (13%) withdrawn as a result of adverse events during the open-label period and three (2%) escitalopram-treated patients and six (4%) placebo-treated patients during double-blind treatment (not significant). The overall withdrawal rate, excluding relapses, was 7.2% for escitalopram and 8.5% for placebo during the double-blind period (not significant).\n Escitalopram was effective in preventing relapse of MDD in older patients and was well tolerated as continuation treatment.", "Despite a growing use of selective serotonin reuptake inhibitors in older people, only one trial has examined their prophylactic efficacy in people aged 65 years and over.\n To examine the efficacy of sertraline in preventing the recurrence of depression in older people living in the community.\n Participants were openly treated with sertraline and then randomised into a double-blind, placebo-controlled continuation/maintenance study of about 2 years duration. Drug dosage was maintained at levels that achieved remission.\n No significant difference between the sertraline and placebo groups was found in the proportion of recurrences (-7.9%; 95% CI -28.06 to 12.23). Increased age and minor residual symptoms during the continuation phase were associated with recurrence.\n Sertraline at therapeutic dosage does not provide significant protection against recurrence.", "The highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment.\n To compare the prophylactic efficacy of citalopram and placebo in elderly patients; to evaluate long-term tolerability of citalopram.\n Out-patients, > or =65 years, with unipolar major depression (DSM-IV: 296.2 x or 296.3 x) and Montgomery-Asberg Depression Rating Scale score > or =22 were treated with citalopram 20-40 mg for 8 weeks. Responders continued on their final fixed dose of citalopram for 16 weeks before randomisation to double-blind treatment with citalopram or placebo for at least 48 weeks.\n Nineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence. Time to recurrence was significantly different between citalopram- and placebo-patients, in favour of citalopram (log-rank test, P<0.0001). Long-term treatment was well tolerated.\n Long-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated.", "Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability.\n To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years.\n A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist.\n University-based psychiatric research clinic.\n Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions.\n Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22).\n Recurrence of major depressive episode.\n The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years.\n In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.", "To standardise the delivery of a brief group cognitive behaviour therapy intervention (CBT-G). To apply the intervention in a research setting and to estimate its effect on recurrence rates in recently depressed older adults, in preparation for a definitive study.\n A CBT-G therapy manual was produced and the Cognitive Therapy Rating Scale (CTS-R) modified to assess therapy delivery. Forty-five adults aged 60 and over who had met ICD-10 criteria for major depression in the previous year and were still taking antidepressant medication were randomly allocated to CBT-G/antidepressant combination or antidepressant alone. Depression severity was measured at baseline, randomisation and 6 and 12 months after start of CBT-G using the Montgomery Asberg Rating Scale for Depression (MADRS).\n One-year recurrence rates on the MADRS were encouragingly lower in participants receiving CBT-G [5/18 (27.8%)] compared with controls [8/18 (44.4%)] although this did not achieve statistical significance (adjusted RR 0.70 [95% CI 0.26-1.94]). In contrast, overall scores on the secondary outcome measure, the Beck Depression Inventory, increased in participants receiving CBT-G. The CBT-G manual was successfully implemented and therapy delivery achieved an overall satisfactory level of competence. We believe that evaluation of this promising intervention in a full-scale trial is warranted.\n (c) 2008 John Wiley & Sons, Ltd.", "Of 219 elderly patients with a major depressive disorder (meeting RDC), 69 recovered sufficiently and consented to enter a two-year double-blind placebo-controlled trial of dothiepin. Survival analysis revealed that dothiepin reduced the relative risk of relapse by two and a half times. Past but not current serious physical illness was also associated with a favourable outcome, whereas a prolonged index depressive illness trebled the relative risk of relapse. In the light of previous research on prognosis it is suggested that elderly persons who recover from a major depressive illness should continue with antidepressant medication for at least two years, if not indefinitely." ]

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[ "Comparative clinical investigation of the tooth whitening efficacy of two tooth whitening gels.", "Comparative clinical evaluation of two professional tooth-whitening products.", "Clinical comparison of Colgate Platinum Toothwhitening System and Rembrandt Gel Plus.", "Clinical evaluation of bleaching agents of different concentrations.", "A clinical evaluation of 10 percent vs. 15 percent carbamide peroxide tooth-whitening agents.", "Efficacy of a novel, nontray, paint-on 18% carbamide peroxide whitening gel.", "A six-month study of two self-applied tooth whitening products containing carbamide peroxide.", "Tooth-whitening efficacy and safety: a randomized and controlled clinical trial.", "A clinical investigation of the efficacy of a tooth-whitening gel.", "Initial color change and color retention with a hydrogen peroxide bleaching strip.", "Comparative clinical efficacy of two professional bleaching systems.", "Clinical evaluation of Colgate Platinum Professional Toothwhitening System and Rembrandt Lighten Bleaching Gel.", "Vital bleaching with a thin peroxide gel: the safety and efficacy of a professional-strength hydrogen peroxide whitening strip.", "Clinical response of three whitening products having different peroxide delivery: comparison of tray, paint-on gel, and dentifrice.", "Comparative efficacy and tolerability of two direct-to-consumer tooth whitening systems.", "A randomized clinical trial comparing a novel 5.3% hydrogen peroxide whitening strip to 10%, 15%, and 20% carbamide peroxide tray-based bleaching systems.", "Randomized clinical trial comparing overnight use of two self-directed peroxide tooth whiteners.", "Comparison of clinical efficacy and safety of three professional at-home tooth whitening systems.", "Comparative tooth whitening efficacy of 18% carbamide peroxide liquid whitening gel using three different regimens.", "Clinical comparison of two self-directed bleaching systems.", "Vital bleaching with two at-home professional systems.", "Clinical evaluation of a new 10% carbamide peroxide tooth-whitening agent.", "Comparison of two over-the-counter tooth whitening products using a novel system." ]

[ "The objective of this randomized, double-blind, parallel-group clinical study was to compare the tooth whitening efficacy of two tooth whitening gel products--Colgate Simply White Night Clear Whitening Gel containing either 25% carbamide peroxide, or 8.7% hydrogen peroxide--when used once daily at night.\n Following a baseline tooth shade evaluation using the Vita Shade Guide, qualifying adult male and female subjects from the Central New Jersey area were randomized into two treatment groups, which were balanced for baseline Vita Shade Guide scores, gender and age. The treatment groups were: 1) a tooth whitening gel containing 25% carbamide peroxide; or 2) a tooth whitening gel containing 8.7% hydrogen peroxide. All subjects were given a commercially available, non-whitening dentifrice and a soft-bristled toothbrush at the beginning of the study. In addition, they were also given one of the two tooth whitening gel products. All subjects were instructed to brush their teeth for one minute twice daily (morning and evening) with the non-whitening toothpaste. The subjects were further instructed to apply their assigned tooth whitening gel product once daily at night, per the instructions provided. Evaluations of tooth shade for each subject were repeated after two weeks, and again after three weeks of product use.\n Fifty-nine (59) subjects complied with the protocol and completed the three-week study. At both the two-week and three-week examinations, all subjects exhibited statistically significant (p < 0.05) tooth shade lightening relative to baseline tooth shade. Further, there was no statistically significant difference in tooth shade lightening between the two tooth whitening gel products.\n The results of this clinical study indicate that after once daily use at night for two or three weeks, a tooth whitening gel containing 25% carbamide peroxide and a tooth whitening gel containing 8.7% hydrogen peroxide both provided statistically significant tooth shade lightening relative to baseline tooth shade. The results also showed that there was no statistical difference in tooth whitening efficacy between the two tooth whitening gel products.", "A 2-week study was conducted to compare the tooth-whitening efficacy of two 10% carbamide peroxide products: Colgate Platinum Professional Toothwhitening System and Rembrandt Lighten Bleaching Gel. Fifty subjects were divided into two groups and assigned a product to use for 2 weeks. Change in tooth color was measured by reflectance spectroscopy at the initiation of study, at 1 week, and at 2 weeks into the study. Color change was calculated using the color-difference equation established by the Commission International de L'Eclairage. Results showed that Colgate Platinum was 62% more effective at tooth whitening after 1 week and 83% more effective after 2 weeks of treatment vs Rembrandt. At the termination of the study, the mean color difference (deltaE) for Colgate Platinum was 4.29 and 2.34 for Rembrandt. Statistical analysis demonstrated that the Colgate product is significantly superior at increasing tooth whiteness, increasing tooth lightness, reducing redness, and reducing yellowness. In this study, no adverse reactions were noted on clinical examination and none were reported by panelists with normal healthy dentition.", "A 2-week, three-cell study was conducted to evaluate the tooth-whitening efficacy of the Colgate Platinum Professional Toothwhitening System vs Rembrandt Gel Plus (a regimen of products consisting of a 10% carbamide peroxide gel, a whitening toothpaste, and a mouthrinse), and a placebo paste. Seventy subjects completed this parallel, single-blind, three-compartment, randomized clinical study. The subjects were balanced into two groups based on a minimal shade of A3 on the Vita shade guide and assigned a product. The duration of product usage was 1 hour twice daily for 2 weeks. Change in tooth color was measured by reflectance spectroscopy using a colorimeter. The readings were taken in the L*, a*, b* color space at the initiation, at 1 week, and at 2 weeks of the study. Calculation of color change (delta E) was performed using the color difference equation established by the Commission Internationale de L'Eclairage. Visual evaluation of shade changes was performed using the Vita shade guide. Results from this clinical study showed that Colgate Platinum was 77.7% more effective at tooth whitening after 1 week and 41.8% more effective after 2 weeks of treatment vs the Rembrandt regimen. Results showed that the Colgate product is significantly superior vs Rembrandt at increasing tooth whiteness (increase in delta E). Shade guide changes showed an overall improvement of 7.08 Vita tabs for the Colgate product and 5.12 Vita tabs for the Rembrandt regimen.", "The purpose of this study was to evaluate the degree of color change, any rebound effect, and sensitivities associated with using 2 different concentrations of carbamide peroxide in vivo.\n Twenty-five subjects used 10% and 15% agents in trays for 14 days on different sides of their maxillary arches. Subjects returned in 3 days and at 1, 2, 3, and 6 weeks for evaluation of color change and rebound effect. Shade matching, photographic means, and a colorimeter were used for evaluation. Subjects self-reported gingival and tooth sensitivity on a scale of 1 (no sensitivity) to 5 (severe sensitivity).\n After 2 weeks, delta L*, delta a*, delta b*, delta E* and delta shade guide rank means for the 10% whitening agent were 6.50, -1.37, -4.63, 8.79, and -15.40, respectively; for the 15% agent, they were 8.72, -1.63, -5.90, 11.03, and -16.59, respectively. After 6 weeks, delta L*, delta a*, delta b*, delta E*, and delta shade guide rank means for the 10% whitening agent were 3.04, -0.99, -3.19, 5.13, and -13.13, respectively; for the 15% agent, they were 3.48, -1.01, -3.60, 5.58, and -13.65, respectively. Means for gingival sensitivity were 1.18 and 1.21 for the 10% and 15% agents, respectively; means for tooth sensitivity were 1.21 and 1.26 for the 10% and 15% agents, respectively.\n All 3 methods of evaluation revealed a significant difference in the tooth lightness achieved by 10% and 15% products at 2 weeks but no significant difference at 6 weeks. No statistically significant difference was found in gingival or tooth sensitivity.", "Agents with carbamide peroxide, or CP, in various concentrations are widely prescribed for at-home tooth whitening. It is not clear, however, if the more concentrated gels will whitening teeth to a greater extent, as no controlled clinical trials have been reported. The authors conducted a double-blind study of human subjects to evaluate whether a 15 percent CP tooth-whitening system was more effective than a 10 percent CP system, and to determine if tooth sensitivity increased with use of the higher concentration.\n The authors recruited 57 subjects with maxillary anterior teeth of shade A3 or darker (as gauged against a value-oriented shade guide). The subjects were 18 to 65 years of age and in good general and dental health. After matching the subjects by sex and age, the authors randomly assigned them to either a control group, which used a 10 percent CP whitening agent, or an experimental group, which used a 15 percent CP agent.\n The results indicated that there was no significant difference in shade change between the groups after one week of treatment (t = 1.455, P = .05), but there was a significant difference at the end of the treatment period (t = 2.303, P < .05), as well as two weeks after treatment concluded (t = 2.248, P < .05). There was no significant difference in sensitivity (t = 1.399, P > .05).\n There was a significant difference in color change between the 10 percent CP and 15 percent CP groups at the end of the study period. There was no significant difference in level of tooth sensitivity between the two groups, and the incidence was equal; there was, however, a significant difference in variability of tooth sensitivity between the two groups.\n If performed under the careful guidance of a dentist, at-home whitening is an effective treatment, regardless of whether 10 percent CP or 15 percent CP is used. There may be added color change and varying sensitivity with the use of 15 percent CP.", "A double-blind, 3-week, randomized, placebo-controlled, parallel-group clinical trial was conducted to evaluate the tooth-whitening efficacy of a novel nontray, \"paint-on\" liquid whitening gel containing 18% carbamide peroxide (Colgate Simply White Clear Whitening Gel). Efficacy was based on measured Vita tooth-shade scores collected at baseline and after 2 and 3 weeks of product use. Eighty healthy volunteers were balanced into 2 groups based on gender, age, and shade scores (A3 or higher). The duration of product usage was 30 minutes, twice daily, for 3 weeks. Results from this clinical study showed that subjects' teeth in the liquid whitening gel-treated group exhibited an overall mean 3.84-shade improvement and a 3.5-shade difference compared with teeth in the placebo gel group (statistically significant, P < .05) after 3 weeks. Furthermore, this improvement exceeds the minimum requirement to claim \"clinical efficacy\" as established by the \"Guidelines for the Acceptance of Peroxide-Containing Oral Hygiene Products,\" published by the American Dental Association in 1994. Therefore, it can be concluded that Colgate Simply White Clear Whitening Gel significantly whitens teeth.", "Bleaching offers a non-interventive way of improving the appearance of sound, yet discolored anterior teeth. Until recently, the whitening agent was applied using a tray, but now other methods of delivering whitening agents, such as those using brush applicators, are available. This study investigated the tooth whitening efficacy of two novel, self-applied tooth whitening systems containing either 18% (Group 1) or 16.4% (Group 2) carbamide peroxide. Ninety-five subjects, ranging in age from 18 to 70 with anterior teeth A3 or darker, were recruited and randomly allocated to a group. The subjects were instructed to apply the formulation to all maxillary anterior teeth after brushing in the morning and evening. At baseline, two weeks and six months the upper six anterior teeth of the subjects were measured using the Vita shade guide tab system. In addition, the gingival health of the labial surfaces of the upper six anterior teeth was assessed using the Loee and Silness Gingival index (Loee & Silness, 1963) at baseline and at two weeks. The mean (SD) reduction in shade guide scores was 4.1 (2.4) shade guide tabs for subjects in Group 1, compared to 3.7 (2.6) shades for those in Group 2. This difference was not statistically significant (p=0.5). During the course of study, the gingivitis scores reduced from a mean (SD) of 0.91 (0.62) at baseline to 0.44 (0.55) at final examination (48% reduction). At the six-month recall, the mean (SD) reduction in shade guide scores was 2.3 (2.7) shade guide tabs for subjects in Group 1, compared to 2.5 (2.5) shades for those in Group 2. The different concentrations tested were found to be equally effective in improving the whiteness of upper anterior teeth by approximately four shades over a two-week period and the majority of the whitening benefit (c.60%) was sustained at six-month recall.", "A randomized, single-center, double-blind, parallel-group, placebo-controlled trial evaluated the whitening efficacy and safety of 2-week, twice-daily use of a 5.3% hydrogen peroxide tooth-bleaching gel delivered on polyethylene film. Efficacy was based on change in Vita shade scores from baseline to the end of treatment. Thirty-three patients in each group completed treatment. Use of the peroxide-containing gel led to a mean change in baseline Vita shade score of -3.70 +/- 0.35, compared with a change of -0.87 +/- 0.24 after use of a placebo gel. After adjustment for baseline scores, the mean difference in shade change between the peroxide gel-treated group and placebo-treated group was -2.85 +/- 0.41 (P < 0.0001). Both treatments were generally well tolerated. The strips offer ease of use, comfort, and shorter duration of wear compared with other at-home bleaching systems.", "The objective of this randomized, controlled, examiner-blind, parallel-group clinical study was to determine whether a tooth-whitening gel (Colgate Simply White Night Clear Whitening Gel) can significantly lighten teeth when used once daily at night, as compared with a commercially available dentifrice. Following a baseline tooth shade evaluation using the VITA Shade Guide, qualifying adult male and female subjects from the Buffalo, New York area were randomized into 2 treatment groups, which were balanced for baseline VITA Shade Guide scores, gender, and age. The treatment groups were: (1) a commercially available dentifrice only; and (2) a tooth-whitening gel in addition to a commercially available dentifrice. Subjects assigned to the 2 groups were given the dentifrice and a soft-bristled toothbrush. In addition, subjects in one of the groups were given the tooth-whitening gel. All subjects were instructed to brush their teeth for 1 minute twice daily (morning and evening) with the dentifrice. The subjects in the group also using the tooth-whitening gel were further instructed to apply the gel once daily at night, as per manufacturer instructions. Evaluations of tooth shade for each subject were repeated after 2 weeks, and again after 3 weeks of product use. In addition, evaluations of tooth shade for subjects using the tooth-whitening gel were later conducted at 6 months after product use. Seventy-five subjects complied with the protocol and completed the study. At the 2-week and 3-week examinations, subjects using the tooth-whitening gel and dentifrice exhibited statistically significant (P < .05) tooth shade lightening relative to baseline tooth shade. Furthermore, at the 2-week and 3-week examinations, subjects using the tooth-whitening gel exhibited statistically significant (P < .05) tooth shade lightening relative to subjects using only the dentifrice. In addition, the 6-month-postuse examination showed that subjects using the tooth-whitening gel exhibited statistically significant (P < .05) tooth shade lightening relative to baseline, thereby maintaining the tooth shade lightening that was evident at 3 weeks. The results of this clinical study indicate that after once-daily use at night for 2 or 3 weeks, the tooth-whitening gel provided statistically significant tooth shade lightening relative to baseline tooth shade for up to at least 6 months and also provided statistically significant tooth shade lightening relative to a commercially available dentifrice after 2 and 3 weeks of product use.", "A randomized, double blind clinical trial was conducted to evaluate initial color improvement and post-treatment color retention following vital bleaching with a strip-based tooth whitening system.\n After balancing for baseline color, 57 healthy adults were randomized to either whitening strips with a 5.3% hydrogen peroxide bleaching gel (Crest Whitestrips) or placebo strips without hydrogen peroxide. Maxillary and mandibular anterior teeth were treated twice daily for 30 minutes each over a 2-week period, and efficacy was measured objectively by comparing digital images of teeth collected at baseline, end-of-treatment (Week 2) and 6 months after treatment (Month 6).\n The whitening strip group experienced a highly significant (P< 0.0001) reduction in yellow of -2.0 deltab* units versus baseline and -1.95 deltab* units versus placebo, with similar results noted for the other color parameters in the study. Most of the initial color change remained at 6 months post-treatment, with the whitening strip group continuing to demonstrate highly significant (P< 0.0001) improvements in tooth color relative to baseline and placebo. Age was found to significantly contribute to initial color improvement, with younger subjects experiencing a greater initial reduction in yellowness compared to older participants, but not to post-treatment color retention. The whitening strips were well tolerated, with minor tooth sensitivity and oral irritation representing the most common findings during treatment. There were no persistent or new treatment-related adverse events during the 6-month monitoring period.", "A randomized, parallel, examiner-blind clinical trial was conducted to compare two professionally dispensed vital bleaching systems. A total of 20 subjects were randomized to either the Crest Professional Whitestrips system or the Nite White Excel 2 tray system, balancing for baseline tooth color. During the 2-week treatment period, subjects were instructed to use the strip system for one-half hour twice daily (14 contact hours) and the tray system for 2 hours daily (28 contact hours). Only the maxillary teeth were treated, and all bleaching was unsupervised. Whitening was measured objectively by comparing digital images of the maxillary anterior dentition at pretreatment and posttreatment. Compared with baseline, both the strip and tray systems exhibited statistically significant decreases (P < 0.05) in yellowness (delta b*) and increases in brightness (delta L*). Compared with the tray-system group, the strip-system group experienced significant additional whitening (P < 0.03), as evidenced by a 62% to 209% improvement in tooth color (delta b*, delta L*, and delta E*) after 14 days. Both systems were generally well tolerated, and none of the subjects discontinued treatment early because of an adverse event. Under the conditions tested, this clinical trial demonstrates that the 14-contact-hour treatment with the strip system resulted in superior whitening efficacy compared with the 28-contact-hour treatment with the tray system.", "A 2-week study was conducted to evaluate the tooth-whitening efficacy of Colgate Platinum Professional Toothwhitening System vs Rembrandt Lighten Bleaching Gel. Thirty-eight subjects completed this single-blind, randomized, parallel clinical study. The subjects were balanced into two groups based on a minimal shade of A3 on the Vita shade guide. The duration of product use was 30 minutes, twice daily for 2 weeks. Change in toodth color was measured by reflectance spectroscopy using a colorimeter. The readings were taken in the L*, a*, and b* color space at the initiation of the study, at 1 week, and at 2 weeks. Calculation of color change (deltaE) was performed using the color difference equation established by the Commission International de L'Eclairage. Results demonstated that Colgate Platinum was 46% more effective at tooth whitening after 1 week, and 96% more effective after 2 weeks of treatment. The results demonstrated that the Colgate product was significantly superior vs Rembrandt at increasing tooth whiteness (increase in deltaE), and tooth lightness (increase in deltaL*). No adverse reations were noted on clinical examination.", "Use of higher peroxide concentrations for professional at-home vital bleaching often balances two factors in patient compliance: whitening and tolerability. Development of a polyethylene strip coated with a very thin (0.10-millimeter) layer of 14 percent hydrogen peroxide gel (Crest Whitestrips Supreme, Procter & Gamble, Cincinnati)--which represents an increase in concentration and a decrease in amount of gel--was believed to allow for greater at-home whitening with little additional oral soft-tissue exposure to peroxide.\n The authors conducted a randomized, double-blind, two-week clinical trial with 38 adults to evaluate the safety and efficacy of twice-daily use of the thin, concentrated bleaching gel strip versus the effects of a control product (Crest Whitestrips, Procter & Gamble). The two products differed only in concentration (14 percent versus 6 percent) and gel layer thickness (0.10 mm versus 0.20 mm). The authors measured efficacy from digital images using the Commission Internationale de l'Eclairage L*a*b* color scale. They assessed safety via subject interviews and clinical examination and compared treatments using analysis of covariance.\n Relative to baseline color, both strip groups exhibited significant (P < .001) improvement in yellowness, brightness and composite color change. Between-group comparisons after two weeks demonstrated significant (P < .003) color improvement for the experimental strip relative to the control. Both products were well-tolerated generally. Despite the concentration differences, clinical examination of each group showed a similar low level (11 percent) of \"minor oral irritation.\"\n Use of the thin 14 percent hydrogen peroxide gel strip resulted in greater whitening, including 42 to 49 percent greater improvement in tooth color and faster whitening onset than that seen with a 6 percent hydrogen peroxide whitening strip, without clinical evidence of increased oral-tissue irritation.\n Use of whitening strips with a thin, concentrated layer of hydrogen peroxide gel may represent a useful approach for professionally directed at-home vital bleaching.", "Comparative clinical research was conducted to evaluate the efficacy and safety of three peroxide-containing tooth whitening products having different peroxide delivery.\n A total of 43 healthy adults who met entrance criteria were randomly assigned to either a dual-phase, anticavity, 1% hydrogen peroxide dentifrice with a manganese gluconate activator, an 18% carbamide peroxide paint-on gel, or a 5% carbamide peroxide professional custom tray system. Following manufacturer's instructions, the activated dentifrice was used at least twice daily for two minutes, while the paint-on gel was applied twice daily. The custom tray, a barrier system and the experimental control for this study, was worn continuously for six to eight hours daily. Tooth color (L*a*b*) was measured on the maxillary anterior teeth from standard digital images, while safety was assessed from examination and subject report.\n At Day 15, the custom tray group had a significant (p < 0.002) reduction in yellowness and increased lightness, with adjusted mean (SE) deltab* of -1.83 (0.210) and deltaL* of 1.45 (0.292). The custom tray group experienced on average greater color improvement compared to either the paint-on gel or activated peroxide whitening dentifrice, differing significantly (p < 0.01) from either of the barrier-free systems with respect to deltab*, deltaL*, deltaE*, and deltaW*. In comparison, 14-days' use of the paint-on gel and activated dentifrice did not result in significant (p > 0.10) color improvements from baseline for deltab*, deltaL*, or deltaW*, with these two barrier-free systems not differing significantly (p > 0.26) with respect to any individual or composite color parameters. Tooth sensitivity and oral irritation were the most common safety findings in the tray and dentifrice groups (there were no adverse events in the paint-on group), and no subject discontinued treatment early because of a treatment-related adverse event.\n In head-to-head 14-day testing, a low concentration (5% carbamide peroxide) barrier-based tray system yielded superior tooth color improvement compared to two barrier-free delivery systems-an 18% carbamide peroxide paint-on gel and a 1% hydrogen peroxide dentifrice with a metal activator.", "To compare the clinical response of two self-directed vital bleaching systems under market use conditions.\n A randomized, parallel-group clinical trial was conducted. A total of 20 healthy adults were randomized to either a 6.0% hydrogen peroxide strip-based bleaching system or a combination system involving a 10% carbamide peroxide gel in a stock tray along with an anticavity whitening dentifrice and after-bleaching whitening mouthrinse. Only the maxillary arch was bleached over a 14-day period. Subjects were evaluated at 3, 8 and 15 days. Efficacy was measured objectively using digital image analysis to derive individual color parameters (L*a*b*) and overall color change (deltaE*).\n After 14 days, the adjusted mean reduction in yellow (Ab*) was -2.23 +/- 0.157 for the whitening strips compared to -0.97 +/- 0.188 for the combination system. This represented a highly statistically significant (P< 0.0001), two-fold superior reduction in yellowness for the whitening strip group compared to the marketed control. Similar results were seen for other color parameters, with the whitening strip group exhibiting two-fold color improvement relative to the tray/dentifrice/rinse combination. With respect to tolerability, tooth sensitivity and oral irritation were the most common findings. Considering event duration and severity, median bleaching tolerability severity-days scores were 0.07 and 0.58 for the strip and combination systems respectively, with these treatments differing statistically (P= 0.04 1) favoring the whitening strips.", "A randomized and controlled, parallel-group clinical trial compared the whitening benefits of a novel 5.3% hydrogen peroxide bleaching strip to 10%, 15%, and 20% carbamide peroxide tray-based bleaching systems. A total of 36 healthy adults were randomized to a 14-day regimen in which both arches were whitened for 1 hour per day in the whitening-strip group or 2 hours per day in the tray groups. Efficacy was measured objectively using digital images of the anterior teeth at baseline and after 14 days of treatment. Overall tooth color (L*a*b*) was derived from individual pixel values, and then mean levels of delta b*, delta L*, and composite color (delta E*) were compared using analysis of covariance. After 14 days of treatment, all groups experienced a greater than 1-unit mean improvement in delta b*, delta L*, and delta E* relative to baseline. For the primary study variable, reduction of yellow (delta b*) outcomes after 14 hours of using the experimental strip were comparable to those observed with the 10% tray group after 28 hours of use. These two treatment groups did not differ statistically with respect to any of the color measurements used in this study. For the tray groups, there was a reasonable dose relationship for the primary end point, delta b*, with the 15% and 20% tray groups averaging 17% and 68% improvements in yellow, respectively, over the 10% group. Except for the 20% carbamide peroxide system, where sensitivity was relatively common, all test products were well tolerated. In this first comparative evaluation vs marketed controls, use of the whitening strips twice daily for 14 days yielded a highly significant improvement in tooth color vs baseline.", "To directly compare tooth color change and spatial uniformity of two brush-applied, peroxide-based overnight tooth whiteners in a 2-week randomized clinical trial.\n 57 adult volunteers were randomly assigned to Crest Night Effects, a 19% sodium percarbonate system packaged in unit dose sachets that when applied, dries to form an adherent film, or Colgate Simply White Night, a paint-on liquid in an applicator bottle at a concentration of 8.7% hydrogen peroxide. Both groups applied their assigned gel on the facial surfaces of the six maxillary anterior teeth for 14 nights. Efficacy was measured objectively as change in L*a*b* tooth color from standard digital images of maxillary teeth, while safety was evaluated by clinical examination and interview.\n After 14 nights treatment, adjusted mean (SE) change in yellowness (delta b*) was -0.95 (0.092) for the 19% sodium percarbonate film and -0.17 (0.096) for the 8.7% hydrogen peroxide gel, with these groups differing statistically (P < 0.0001). Other individual and composite color parameters also demonstrated significantly greater whitening for the 19% sodium percarbonate film compared to the 8.7% hydrogen peroxide gel after 14 nights use. Only the 19% sodium percarbonate film exhibited significant (P< 0.0001) proximal color improvement (delta b*) after 2 weeks, approximately 98% of that seen on the body of the tooth, providing evidence of proximal bleaching and uniform spatial whitening following use of this barrier-free system. Both products were well-tolerated, with no subjects discontinuing treatment early due to a causal adverse event.", "A three-cell, randomized, parallel, investigator-blinded clinical trial was conducted to compare the efficacy and safety of three professional at-home tooth whitening systems, including Crest Professional Whitestrips (6.5% H2O2), Day White 2 (7.5% H2O2) and Nite White Excel 2 (16% carbamide peroxide equivalent). Ninety subjects were randomly assigned to three groups (30/group). Subjects were instructed to use the assigned whitener following the manufacturers' instructions. Clinical examinations at baseline, and on days 3, 7, 14, and 18 (Day White), or 21 (Crest Professional Whitestrips and Nite White) included the following parameters: 1) oral tissues; 2) tooth shade by the Vitapan Classical shade guide; 3) tooth shade by a chromameter with a jig; and, 4) tooth sensitivity and gingival irritation. The results showed significant shade reductions with time in all three groups. Nite White resulted in significantly greater shade reductions in periods between days 7, 14, or 21 and baseline than did the other two systems. Tooth sensitivity and gingival irritation, which were mostly mild and transient, occurred in all groups. It is concluded that all three whitening systems evaluated are effective and safe. Nite White Excel is superior to the other two systems because it provides a greater whitening efficacy with comparable or lower incidence of tooth sensitivity and gingival irritation.", "Recently, a novel paint-on liquid whitening gel--Colgate Simply White Clear Whitening Gel--which contains 18% carbamide peroxide, has been developed as a self-administered tooth bleaching system. The purpose of the present study was to determine the efficacy and safety of this product using alternate exaggerated or simplified treatment regimens.\n This was a three-week clinical trial using a parallel, double-blind, stratified protocol with three different instructions for application: 1) twice-daily, no air-drying, and 15 minutes without eating/drinking; 2) three times daily, 30-second air-drying and 30 minutes without eating/drinking; or 3) four times daily, 30-second air-drying and 30 minutes without eating/drinking. One-hundred and twenty (120) healthy volunteers were balanced into three equal groups based on shade scores (A3 or darker). Clinical evaluations (shade guide, oral tissue health, gingival index and visual analog sensitivity score) were performed on each group at baseline and weekly for the next 21 days. At the conclusion of the study, a survey of the subjects' opinions on their assigned product regimen was also conducted.\n Subjects who used Colgate Simply White Clear Whitening Gel three and four times daily achieved the greatest shade improvement (5.88 +/- 1.53 shades, and 5.57 +/- 1.54, respectively). However, these values were only about one shade better than the value observed for the more convenient, twice-daily, \"no-dry\" regimen (4.51 +/- 1.77 shades), though they were statistically significant (p < 0.05). The result for the four-times daily protocol was not statistically different from the three-times group. Also, no differences were observed between the groups concerning oral tissue health, gingival index or tooth sensitivity, and no adverse effects were observed or reported regardless of the regimen used. Surveys completed by the subjects showed that those who used the twice-daily, \"no-dry\" regimen found the product to be the easiest to use, the most comfortable and the most pleasant tasting.\n It can be concluded from the clinical data that three or four applications of Colgate Simply White Clear Whitening Gel per day provided better efficacy. In addition, the use of the whitening gel twice daily, even without \"dry time\" and only 15 minutes without eating/drinking, yielded results that were comparable to previously reported results using the original on-label directions. The potential additional benefit to the \"simplified regimen\" is that it was perceived to be the most convenient and comfortable. The use of Colgate Simply White Clear Whitening Gel up to four times daily for up to three weeks is also safe, and the tendency of abusing the product with more frequent daily use may be deterred by the inconvenience reported by the study subjects.", "This randomized clinical trial compared the clinical efficacy and tolerability of 2 marketed self-directed vital tooth-whitening systems.\n Balancing for baseline tooth color, self-reported coffee/tea use, and age, 57 adult volunteers were randomized to either a whitening strip containing 6% hydrogen peroxide or a tray-based 10% carbamide peroxide/dentifrice/mouth rinse combination system. Following the manufacturer's directions, the strip group bleached twice daily for 30 minutes, whereas the tray group bleached twice daily for 20-30 minutes, preceded by tooth brushing with a whitening dentifrice and followed by mouth rinsing with a whitening solution. Treatment extended for 14 days, with evaluation at day 7 and again at day 14. Whitening response was measured objectively as L*a*b* from standardized digital images of maxillary anterior teeth. Tolerability was assessed by oral examination and subject interview. Efficacy comparisons were made using analysis of covariance, whereas tolerability was compared using the nonparametric Wilcoxon rank-sum test.\n Both treatments resulted in statistically significant (P < 0.01) improvements from baseline for all color parameters. For between-group comparisons, the 6% hydrogen peroxide strips yielded a nearly 3-fold reduction in yellowness (deltab*), a nearly 2-fold improvement in lightness (deltaL*), 2.6 times greater redness reduction (deltaa*), and a more than 2-fold change in overall color (deltaE*) compared to the tray-based combination system. Between-group comparisons were statistically significant for the all color parameters at both the day 7 and day 14 evaluations (P < 0.001). In general, 7-day use of the whitening strips provided significantly greater color improvement relative to the combination dentifrice/gel/rinse system at day 14. In addition, the groups differed significantly (P < 0.05) in bleaching tolerability severity-days, with the strip system demonstrating better overall tolerability compared to the combination system.\n The single-step 6% hydrogen peroxide strips demonstrated better overall clinical response, in terms of both tooth-whitening efficacy and tolerability, than the multiple-step tray-based combination system.", "To compare the whitening effectiveness of two professional vital bleaching systems in a randomized clinical trial.\n Balancing for baseline color, 6 9 adult volunteers were randomized to either a whitening strip containing 6.5% hydrogen peroxide (Professional Crest Whitestrips) or a custom tray-based system using both hydrogen and carbamide peroxide (Nite White Excel2). Total contact time was 21 hours for the strip system and 28 hours for the 10% carbamide peroxide equivalent tray system. Whitening response was measured objectively as L*a*b* from digital images of the maxillary anterior teeth.\n Both treatments resulted in significant (P < 0.01) improvements in yellowness (deltab*), brightness (deltaL*) and overall color (deltaE*). For between group comparisons, strip subjects had a statistically significant or directionally favorable whitening response relative to the tray system at intermediary time points, while at the end-of-treatment, the strip group had highly statistically significant (P < or = 0.005), superior whitening response for all color parameters measured in the study. Both treatments were generally well tolerated, with 35-40% of the subjects in each group reporting minor tooth sensitivity or gingival irritation.", "NUPRO Gold Tooth Whitening System was evaluated for efficacy according to the proposed ADA guidelines for acceptance. Sixty participants with discolored anterior teeth participated in a 14-day, double-blind, clinical trial. The participants were matched for age, gender, and oral health status and were given either a placebo gel without the active agent or the NUPRO Gold active gel, which they wore in a custom-fabricated mouth guard for home use. The shade of each participant's maxillary anterior teeth was evaluated using a value-oriented Vita Lumin Vacuum Shade Guide before the study. The same shade guide was used to determine shade changes. Time of use of the agent and potential side effects, such as tooth and gingival hypersensitivity and tissue irritation, were assessed at all recall examinations and were recorded by participants in daily diaries. The average shade change for the placebo users was less than one shade. The average shade change for the NUPRO Gold users was 6.96 shades. Tooth hypersensitivity varied from none to severe. Tissue irritation was minimal. The results of these evaluations indicate that NUPRO Gold is effective as a tooth-whitening system, when administered properly under the supervision of a dentist, with commonly reported side effects of transient tooth sensitivity and minimal gingival sensitivity. Little or no change in tissue health was noted. This study was supported by Dentsply Preventive Care (York, Pennsylvania).", "Tooth whitening is one of the most widely accepted esthetic procedures in dentistry. Various treatment options include in-office and prescribed at-home bleaching procedures, over-the-counter bleaching kits, and whitening dentifrices. This study evaluated and compared a 6% hydrogen peroxide tooth bleaching gel delivered on polyethylene film (HP) with an 18% carbamide peroxide brush-applied liquid gel (CP). A total of 59 subjects completed this 2-week, examiner blind, randomized, parallel group study. Both treatments were applied twice daily for 2 weeks according to the manufacturer's instructions. Evaluations for oral safety and Vita tooth shade were conducted by a dental examiner at baseline and 2 weeks after product use. In addition, the ShadeVision System was used to determine changes in Vita shade and L*a*b* values. Based on both the examiner and ShadeVision System assessments, both treatments significantly improved tooth shade. Improvements in Vita tooth shade based on the adjusted mean for HP were 2.64 (P < 0.001) and 2.33 (P < 0.001) for the examiner and ShadeVision System assessments, respectively, compared with improvements of 1.04 (P = .004) and 0.42 (P = 0.029) for CP users, respectively. The difference between treatments was found to be significant for both the examiner (P = .005) and ShadeVision (P = .001) assessments. Findings from the L*a*b* data derived from the ShadeVision System were in agreement with Vita assessments, with significant differences for changes in L*, a*, and b* in favor of HP users (P = .001). In this study, the ShadeVision method of color analysis was relatively easy to use and demonstrated significant differences between 2 OTC whitening products using both Vitapan and L*a*b* means of assessment." ]

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[ "The effect of recombinant human erythropoietin on circulating hematopoietic progenitor cells in anemic premature infants.", "Changes in thrombopoiesis and platelet reactivity in extremely low birth weight infants undergoing erythropoietin therapy for treatment of anaemia of prematurity.", "Recombinant human erythropoietin therapy in low-birthweight preterm infants: a prospective controlled study.", "Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial.", "Use of erythropoietin and its effects on blood lactate and 2, 3-diphosphoglycerate in premature neonates.", "[Evaluation of treatment results for anemia of prematurity treated with various doses of human recombinant erythropoietin].", "An approach to using recombinant erythropoietin for neuroprotection in very preterm infants.", "[Early erythropoietin use for the prevention of anemia in infant premature].", "In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study.", "Follow-up of very low birth weight infants after erythropoietin treatment to prevent anemia of prematurity.", "Recombinant erythropoietin and blood transfusion in selected preterm infants.", "The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 grams or less: a randomized, double-blind, placebo-controlled study.", "Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized, placebo-controlled trial.", "Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.", "Iron supplementation enhances response to high doses of recombinant human erythropoietin in preterm infants.", "Efficacy and safety of recombinant human erythropoietin to prevent the anaemias of prematurity. European Randomized Multicenter Trial.", "[Efficacy of early erythropoietin use in critically ill, very-low-birthweight premature newborn infants: controlled clinical trial].", "The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group.", "Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g.", "Preventive effect of different dosage of recombinant human erythropoietin on anemia of premature infants.", "[Early use of recombinant human erythropoietin promotes neurobehavioral development in preterm infants].", "Erythropoietin concentrations and neurodevelopmental outcome in preterm infants.", "Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity?", "Effects of early human recombinant erythropoietin therapy on the transfusion in healthy preterm infants.", "A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country.", "Effect of recombinant human erythropoietin on transfusion needs in preterm infants." ]

[ "In vitro and animal studies suggest that high concentrations of recombinant human erythropoietin (rHuEPO) might divert multipotent progenitors into erythroid maturation at the expense of granulocyte production. We determined whether changes of number and lineage commitment of peripheral blood progenitor cells occur in premature infants during therapy with rHuEPO. Thirty preterm infants were randomly assigned either to receive 300 IU of eopoetin alpha s.c. per kilogram body weight three times a week for four weeks or to a control group. At study entry and after two weeks of treatment the numbers of circulating BFU-E, granulocyte-macrophage colony-forming units (CFU-GM) and granulocyte-erythrocyte-macrophage-megakaryocyte CFU (CFU-GEMM) were analyzed by semisolid culture technique, CD34+ cells and early myeloid CD34+CD45RA- progenitors by flow cytometry. As compared with the control group, rHuEPO treatment did not exert any significant modulatory effect on numbers of CFU-GM, nor was there a significant change in numbers of BFU-E, CFU-GEMM, total-CFU, percentage of CD34+ or CD34+CD45RA- cells. Mean neutrophil count was not significantly reduced at any period during the study. Compared with the control group, the infants receiving rHuEPO had higher hematocrit values (p = 0.003) and absolute reticulocyte counts (p < 0.001). The median cumulative volume of blood transfused per kilogram per day was 0.86 ml (first quartile 0.5 ml; third quartile 1.1 ml) in the control group and 0 ml (first quartile 0 ml; third quartile 0.47 ml) in the rHuEPO group (p = 0.038). We conclude using a relatively high dose of rHuEPO in premature infants, no significant in vivo effect on circulating peripheral blood progenitor or neutrophil count could be detected.", "Erythropoietin (Epo) is frequently administered to premature infants to stimulate erythropoiesis. There is evidence from studies in animals and healthy adults that Epo also interacts with thrombopoiesis and platelet function. This study investigates the effect of Epo therapy on platelet reactivity, peripheral platelet counts and thiazole orange-positive (TO+) platelets in extremely low birth weight (ELBW) infants. In a randomised-controlled trial, ELBW infants with a birth weight < or =800 g and a gestational age < or =32 weeks were either randomised to a group receiving Epo during the first weeks of life or to a control group. Our results show that thrombin receptor-activating peptide (TRAP-6) -induced expression of P-selectin increased significantly during the first two weeks of Epo treatment. With the exception of week five, the number of TO+ platelets was significantly higher during the first eight weeks in Epo-treated infants compared to controls. The increase of TO+ platelets was not paralleled by an increase in total platelet count. We can conclude that Epo therapy has a short-lasting effect on platelet reactivity toTRAP-6 in ELBW infants during the first two weeks of life. Furthermore, Epo therapy is associated with an increase in the number of TO+ platelets compared to controls.", "This study aimed to detect the effectiveness of recombinant human erythropoietin therapy in preventing premature anemia in low-birthweight preterm infants.\n A total of 292 premature infants who were born earlier than 33 gestational weeks and smaller than 1500 g birthweight were enrolled into the study. In addition to their conventional supportive therapy (medications), recombinant human erythropoietin 200 U/kg twice a week, subcutaneously, was given to randomly selected 142 premature infants for 6 weeks. The blood count variables and need for transfusions were compared with the remaining 150 premature infants during 6 months follow up.\n Serum erythropoietin levels were 11.3 +/- 6.1 mU/mL and 38.3 +/- 19.1 mU/mL in the erythropoietin group before and at the fourth week of the study, respectively (P < 0.001). Reticulocyte counts of the group treated with erythropoietin were 146 x 10(6) +/- 28 x 10(6)/mL and 122 x 10(6) +/- 27 x 10(6)/mL at the fourth and seventh week of the study, respectively, and these values were significantly higher when compared with the control group (P < 0.001 and P < 0.001). At the same period, hematocrit values were also found to be higher in the treatment group than the control group (P < 0.001). Serum ferritin levels were lower in the treatment group compared with the control group at the fourth week of the study. No side-effects related to erythropoietin usage were encountered. The need for packed cell transfusions were 47% in the group treated with erythropoietin and 62.6% in the control group. A statistically significant difference was found for transfusion needs between the control and treatment groups (P < 0.001).\n Recombinant erythropoietin is effective therapy for maintaining stable hematocrit levels in low-birthweight preterm infants and prevents the need for blood transfusions.", "Infants of </=1250 g birth weight receive multiple erythrocyte transfusions during their hospitalization. We hypothesized that early erythropoietin (Epo) and iron therapy would 1) decrease the number of transfusions received (infants 401-1000 g birth weight; trial 1) and 2) decrease the percentage of infants who received any transfusions (1001-1250 g birth weight; trial 2).\n A total of 172 infants in trial 1 and 118 infants in trial 2 were randomized to treatment (Epo, 400 U/kg 3 times weekly) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Complete blood and reticulocyte counts were measured weekly, and ferritin concentrations were measured monthly. Transfusions were administered according to protocol. Phlebotomy losses and transfusion data were recorded.\n Treated and placebo/control infants in trial 1 received a similar number of transfusions (4.3 +/- 3.6 vs 5.2 +/- 4.2, respectively). A similar percentage of treated and control infants in trial 2 received at least 1 transfusion (37% vs 46%). Reticulocyte counts were higher in treated infants during each week of the study in both trials. Hematocrits were higher among treated infants from week 2 on in both trials. Ferritin concentrations were higher in placebo/controls than in treated infants at weeks 4 and 8 in trial 1 and at week 4 in trial 2. No adverse effects of Epo or supplemental iron occurred.\n The combination of early Epo and iron as administered in this study stimulated erythropoiesis in infants who were </=1250 g at birth. However, the lack of impact on transfusion requirements fails to support routine use of early Epo.neonate, intravenous iron, donor exposure.", "The aim of this study was to investigate the effect of recombinant human erythropoietin (rHu-EPO) on oxygen affinity and adequate oxygen delivery to the tissues of stable premature infants. 36 very-low-birth-weight infants were randomly assigned to either receive rHu-EPO (200 units/kg every other day) or not, and both groups were supplemented with iron, folic acid and vitamin E. Arterial blood gases, oxygen saturation, complete blood counts, fetal haemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and blood lactate were analysed weekly, from the 1st week till discharge. Patients in the two groups were comparable. There was a trend in increasing lactate values towards the 4th to 5th weeks of life, which did not reach statistical significance. There was no correlation between lactate values and the studied variables (pH, BE, oxygen saturation). In 35 transfusions, pre- and 24 h post-transfusion blood lactate status was studied. In 23 of them, a decrease in post-transfusion lactate was noticed, whilst an increased post-transfusion level was shown in 10 cases and no change in 2 cases. The mean pre-transfusion lactate value was significantly higher than the post-transfusion one (24.04 +/- 11.9 mg/dl before and 16.27 +/- 8.5 mg/dl after transfusion; p = 0.0025). In both groups there was a steady rise in 2,3-DPG concentration over the period of study, and the 2,3-DPG values at the end of our study were significantly increased in the rHu-EPO group (rHu-EPO 5.98 +/- 0.9, control 4.84 +/- 0.7; p = 0.04). In conclusion, the use of rHu-EPO did not affect blood lactate levels compared to the control group. Regarding oxygen affinity, it seems that rHu-EPO causes a shift of the oxy-haemoglobin dissociation curve to the right. This is a previously unreported effect of rHu-EPO and its clinical use may, thus, confer to preterm babies an added advantage.", "We evaluated the results of administering recombinant human erythropoietin (rHuEPO) and iron in 19 randomly selected premature infants, who had no infections, did receive oxygen support or aminophylline. rHuEPO was administered intravenously from days to 37 (biweekly) in a dose of 100 U/kg (group I) or 400 U/kg (group II). Also, infants in both groups were supplemented with 10 mg/kg/week of iron intravenously. Seven of 19 infants did not receive either rHuEPO or iron (group III). Infants of all groups had similar birth weights, gestational age and hematocrit, RBC count as well as total and fetal hemoglobin concentrations in blood obtained within the first hour of life. However, infants treated with 400 U/kg of rHuEPO required a significantly (p < 0.04) lower volume of packed erythrocytes in comparison to untreated infants, both between days 7 and 37 of life (18.6 ml vs 46.8 ml; p < 0.04) and between day 7 of life and the day of discharge (35.8 ml vs 94.2 ml; p < 0.04). No difference in neutrophil count, fetal hemoglobin concentration and no toxicity were observed in infants treated with rHuEPO in comparison to untreated prematures.", "Erythropoietin has been shown to be protective against hypoxic-ischemic and inflammatory injuries in cell culture, animal models of brain injury, and clinical trials of adult humans. The rationale for our study was that early administration of high-dose recombinant human erythropoietin may reduce perinatal brain injury (intraventricular hemorrhage and periventricular leukomalacia) in very preterm infants and improve neurodevelopmental outcome. We investigated whether administration of high-dose recombinant human erythropoietin to very preterm infants shortly after birth and subsequently during the first 2 days is safe in terms of short-term outcome.\n This was a randomized, double-masked, single-center trial with a 2:1 allocation in favor of recombinant human erythropoietin. Preterm infants (gestational age: 24 to 31 weeks) were given recombinant human erythropoietin or NaCl 0.9% intravenously 3, 12 to 18, and 36 to 42 hours after birth.\n The percentage of infants who survived without brain injury or retinopathy was 53% in the recombinant human erythropoietin group and 60% in the placebo group. There were no relevant differences regarding short-term outcomes such as intraventricular hemorrhage, retinopathy, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. For 5 infants who were in the recombinant human erythropoietin group and had a gestational age of <26 weeks, withdrawal of intensive care was decided (3 of 5 with severe bilateral intraventricular hemorrhage, 2 of 5 with pulmonary insufficiency); no infant of the control group died. Recombinant human erythropoietin treatment did not result in significant differences in blood pressure, cerebral oxygenation, hemoglobin, leukocyte, and platelet count.\n No significant adverse effects of early high-dose recombinant human erythropoietin treatment in very preterm infants were identified. These results enable us to embark on a large multicenter trial with the aim of determining whether early high-dose administration of recombinant human erythropoietin to very preterm infants improves neurodevelopmental outcome at 24 months' and 5 years' corrected age.", "Anemia is common among very low birth weight newborns and requires frequent blood transfusions. Erythropoietin was been reported to be useful in the prevention of this anemia.\n To assess the benefits of early (before the third week of life) Human recombinant Erythropoietin (r-EPO) administration to reduce the requirement of blood transfusions in very low birth weight newborns.\n Sixty newborns under 1500 g of birthweight were randomly assigned to receive r-EPO (n = 29) or placebo (n = 31) three times per week, during four weeks. Packed red cell volume and reticulocyte counts were measured weekly. Serum erythropoietin was measured prior to eighth dose. Transfusion requirements were recorded.\n r-EPO reduced transfusions from 1.41 +/- 1.1 to 0.69 +/- 1 transfusions/newborns (p < 0.001). At the fourth week of treatment, reticulocyte count was 14.8 +/- 7 and 6.4 +/- 4.9% in the active treatment group and placebo group respectively (p < 0.001).\n r-EPO reduces the requirement of transfusions in low birth weight infants.", "To assess whether erythropoietin (EPO) treatment is safe and reduces the need for transfusion, we randomized 44 preterm infants to an EPO group and a comparable control (CON) group. EPO 150 U/kg was given s.c. twice weekly for 6 wk from the 1st wk of life. Hematologic parameters, transfusion requirements, and growth were followed during therapy and for 6 mo thereafter. To better assess in which neonates EPO treatment was effective, we classified retrospectively the EPO and CON groups into uncomplicated neonates (EPO A: n = 9, birth weight = 1247 +/- 126 g, gestational age = 29.8 +/- 1.5 wk; CON A: n = 7, birth weight = 1217 +/- 145 g, gestational age = 29.9 +/- 1.5 wk) and neonates requiring artificial ventilation (EPO B: n = 16, birth weight = 1169 +/- 249 g, gestational age = 28.1 +/- 2 wk; CON B: n = 12, birth weight = 1173 +/- 215 g, gestational age = 28.3 +/- 2 wk). There were significant differences in reticulocytes between both uncomplicated and ventilated neonates in the EPO group compared with respective control groups. However, the need for transfusion was significantly less in the uncomplicated EPO group (EPO A: 0.44 +/- 0.73 versus CON A: 1.28 +/- 0.75, p < 0.05) but not in the neonates on ventilation (EPO B: 8.25 +/- 5 versus CON B: 7.75 +/- 3.7). In conclusion, early EPO administration reduces the need for transfusion in uncomplicated premature neonates.(ABSTRACT TRUNCATED AT 250 WORDS)", "Treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis and reduces the need for transfusions in hospitalized preterm infants. The aim of our study was to follow very low birth weight infants after the initial 6 weeks of rHuEPO treatment.\n We randomly assigned 97 very low birth weight infants with a gestational age of 31 weeks or less and birth weight of 1500 gm or less to receive rHuEPO, 300 units/kg per week (erythropoietin (EPO) 300, n = 33), rHuEPO, 750 units/kg per week (EPO 750; n = 28), or no treatment (control, n = 36). The rHuEPO was administered from the first week of life for 6 weeks. After EPO therapy was discontinued, 75 neonates were followed weekly until discharge and at 3, 6, and 12 months of age.\n Mean numbers (+/- SD) of packed erythrocyte transfusions per patient from the time rHuEPO therapy was discontinued until discharge were 0.38 +/- 0.64 (EPO 300), 0.23 +/- 0.52 (EPO 750), 0.9 +/- 1.1 (control) (p < 0.05 in both EPO groups vs control). Mean reticulocyte counts at the sixth week were 6% +/- 2.2% (EPO 300), 6.9% +/- 2.2% (EPO 750), and 3.1% +/- 2.6% (control) in the three groups (p < 0.01 in both EPO groups vs control), and at the eighth week were 4.7% +/- 2.8% (EPO 300), 5.4% +/- 2.7% (EPO 750), and 2.6% +/- 2.2% (control) (p < 0.01 in both EPO groups vs control). Serum ferritin levels were significantly higher at the sixth week, and the percentage of hemoglobin F was significantly lower at 6, 8, and 10 weeks in the control group versus EPO groups. At 3, 6, and 12 months of age, there were no differences in reticulocytes, ferritin, HbF, and growth among groups.\n Preterm infants who received rHuEPO had a normal pattern of erythropoiesis after the drug was discontinued. These data provide strong evidence that the anemia of prematurity is the result of a transient developmental abnormality in EPO production.", "To comprehensively identify preterm infants likely to require blood transfusion and to investigate the effectiveness of recombinant erythropoietin in this high risk subgroup.\n Double blind randomised controlled trial.\n Neonatal Intensive Care Unit, Middlemore Hospital, Auckland, New Zealand.\n Preterm infants < 33 weeks gestation and < 1700 g birth weight meeting specific criteria indicating a high possibility of requiring blood transfusion.\n Predictors of blood transfusion were determined by analysis of preterm infants admitted to a neonatal intensive care unit over a two year period. Using the criteria developed, high risk infants entered the study and received erythropoietin or sham treatment until 34 weeks completed gestation. The sample size was calculated to detect a reduction of one blood transfusion per infant (significance level 5%, power 80%).\n The selection criteria had a positive predictive value for transfusion of 91% and a negative predictive value of 94%. Mean birth weights and gestational ages were similar in the two groups. Absolute reticulocyte counts and haemoglobin values were higher in the group receiving erythropoietin. There was no significant difference in the number of blood transfusions received in the treatment and control groups. However, comparing transfusions given to < 1000 g infants after 30 days of age, there were significantly fewer transfusions in the erythropoietin group (mean (SD) 0.5 (0.7) in those receiving erythropoietin and 1.6 (1.1) in the controls). No adverse effects were noted.\n The selection criteria for the study were highly predictive of subsequent transfusion. In the group receiving erythropoietin, a reduction in transfusion requirements was apparent only in the < 1000 g birthweight group after 1 month of age.", "Clinical trials of erythropoietin (EPO) administration to preterm infants have not focused on infants weighing 750 gm or less, the population most likely to receive multiple transfusions because of large phlebotomy losses. It is unknown whether preterm infants weighing 750 gm or less will respond to EPO by accelerating erythropoiesis, or whether EPO administered to this population will decrease blood transfusions.\n We randomly assigned 28 extremely low birth weight preterm infants (mean +/- SEM: 24.7 +/- 0.3 weeks' gestation, 662 +/- 14 gm birth weight), in the first 72 hours of life, to receive either EPO (200 U/kg/day) or placebo for 14 days and administered transfusions only according to protocol over a 21-day study period. All infants received 1 mg/kg/day iron dextran in their total parenteral nutrition solution during the 14-day treatment period.\n During the 21-day study period, a lower number and volume of transfusions were received by the EPO recipients (4.7 +/- 0.7 transfusions per patient and 70 +/- 11 ml/kg per patient) than by the placebo recipients (7.5 +/- 1.1 transfusions per patient and 112 +/- 17 ml/kg per patient; p < 0.05, EPO vs placebo), whereas hematocrits remained similar in the two groups. Reticulocyte counts were similar in both groups on day 1 but were greater in the EPO recipients on day 14 (EPO day 1, 351 +/- 53; EPO day 14, 359 +/- 40 x 10(3)/microl; placebo day 1, 334 +/- 64; placebo day 14, 120 +/- 10 x 10(3)/microl; p < 0.01, EPO vs placebo). Serum ferritin concentrations were similar in both groups at the beginning of the study but were greater in the placebo recipients by day 14 (EPO, 262 +/- 44 microg/L; placebo, 593 +/- 92 microg/L; p < 0.01). No adverse effects of EPO or iron were noted.\n The combination of EPO and parenteral iron stimulates erythropoiesis in preterm infants weighing 750 gm or less and results in fewer transfusions during their first 3 weeks of life.", "We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective.\n We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia.\n On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group.\n We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective.", "To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.", "To determine whether iron supplementation would enhance erythropoiesis in preterm infants treated with high doses of human recombinant erythropoietin (r-HuEPO).\n Sixty three preterm infants were randomly allocated at birth to one of three groups to receive: r-HuEPO alone, 1200 IU/kg/week (EPO); or r-HuEPO and iron, 1200 IU/kg/week of r-HuEPO plus 20 mg/kg/week of intravenous iron (EPO + iron); or to serve as controls. All three groups received blood transfusions according to uniform guidelines.\n Infants in the EPO + iron group needed fewer transfusions than controls--mean (95% CI) 1.0 (0.28-1.18) vs 2.9 (1.84-3.88) and received lower volumes of blood--mean (95% CI) 16.7 (4.9-28.6) vs 44.4 (29.0-59.7) ml/kg. The EPO group also needed lower volumes of blood than the controls--mean (95% CI) 20.1 (6.2-34.2) vs 44.4 (29.0-59.7) ml/kg, but the same number of transfusions, 1.3 (0.54-2.06) vs 2.9 (1.84-3.88). Reticulocyte and haematocrit values from postnatal weeks 5 to 8 were higher in the EPO + iron than in the EPO group, and both groups had higher values than the controls. Mean (SEM) plasma ferritin was lower in the EPO group-65 (55) micrograms/l than in the EPO + iron group 780 (182) micrograms/l, and 561 (228) micrograms/l in the control infants.\n Early administration of high doses of r-HuEPO with iron supplements significantly reduced the need for blood transfusion. Intravenous iron (20 mg/kg/week in conjunction with r-HuEPO yielded a higher reticulocyte count and haematocrit concentration after the forth week of life than r-HuEPO alone. Infants treated with r-HuEPO alone showed signs of reduced iron stores.", "nan", "To determine the efficacy of erythropoietin in very low birth weight (VLBW) newborns less than 72 h of age.\n We randomly assigned 40 critically ill newborn VLBW infants to receive either recombinant human erythropoietin (EPO) 150 units/kg per day (21 patients) or placebo (19 patients) during their first six weeks of life. The observers were unaware of the treatment assignments. Frequency of erythrocyte transfusion, adverse effects and haematologic measures were evaluated and compared.\n Before treatment gestational age, weight, haemoglobin, and pathology were similar in both groups. During the subsequent 6 weeks, haemoglobin and haematocrit of the placebo group fell significantly below those of the EPO recipients. More transfusions were received by the placebo recipients (7/21) than by the EPO recipients (2/21; p = 0.04). No adverse effects of EPO were observed.\n We recommend the administration of recombinant human erythropoietin since the first 72 h of age, because of the high frequency of anaemia, the efficacy of EPO and lack of side effects.", "Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions.\n We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward.\n The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02).\n Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.", "To investigate whether recombinant erythropoietin (rhEPO) reduces the need for transfusion in extremely low birth weight (ELBW) infants (birth weight 500-999 g) and to determine the optimal time for treatment.\n In a blinded multicenter trial, 219 ELBW infants were randomized on day 3 to one of 3 groups: early rhEPO group (rhEPO from the first week for 9 weeks, n = 74), late rhEPO group (rhEPO from the fourth week for 6 weeks, n = 74), or control group (no rhEPO, n = 71). All infants received enteral iron (3-9 mg/kg/day) from the first week. The rhEPO beta dose was 750 IU/kg/week. Success was defined as no transfusion and hematocrit levels never below 30%.\n Success rate was 13% in the early rhEPO group, 11% in the late rhEPO group, and 4% in the control group (P =.026 for early rhEPO versus control group). Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day (P =.02) and median donor exposure was 1.0 versus 1.0 versus 2.0 (P =.05) in the early rhEPO group, the late rhEPO group, and the control group, respectively. Infection risk was not increased and weight gain was not delayed with rhEPO beta.\n Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants.", "To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1,800 g were randomly assigned to treatment group 1 (n = 15, receiving subcutaneous rhEpo 150 U/kg.time), treatment group 2 (n = 15, receiving 250 U/kg.time), three times a week for 6 weeks, and control group (n = 15, no treatment was given). All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P < 0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P < 0.0001 for all), but there was no significant difference between the two treatment groups (P > 0.05). Serum iron dropped significantly in the treatment groups as compared with control group (P < 0.01 for all), but no dose-dependent relationship was observed in treated infants (P > 0.05). After treatment, serum levels of erythropoietin was higher in group 2 than those in group 1 and control group (P < 0.0001, P < 0.01 and P < 0.05, respectively). There was no significant difference between group 1 and control group (P > 0.05). No side effects related to rhEpo therapy were observed. Our study suggested that rhEpo therapy stimulates endogenous erythropoiesis and enhances Ret, Hct and level of Hb in a dose-dependent manner in premature infants. The therapy is more efficient when given in higher dosages.", "To evaluate the effect of the early use of recombinant human erythropoietin (rhu-EPO) on neurobehavioral development in preterm infants.\n Forty-four preterm infants (30 males and 14 females) were randomly divided into two groups: Rhu-EPO treatment and untreated control (n=22 each). From postnatal day 7, the Rhu-EPO treatment group received intravenous rhu-EPO (250 IU/kg3 times weekly) for 4 weeks. A Neonatal Behavioral Neurological Assessment (NBNA) was performed at 40 weeks of corrected gestational age. A Gesell Development Schedule was used to evaluate neurological development 6 and 12 months after birth.\n The NBNA score in the rhu-EPO treatment group (36.20+/-0.75) was significantly higher than that in the control group (34.40+/-1.05) at 40 weeks of corrected gestational age (P<0.05). The developmental quotient of fine motor in the rhu-EPO treatment group was significantly higher than that in the control group 6 months after birth (P<0.05). By 12 months after birth, the developmental quotient of gross motor, fine motor and language in the rhu-EPO treatment group was significantly higher than that in the control group (P<0.05).\n Early use of Rhu-EPO can promote neurobehavioral development in preterm infants.", "Erythropoietin therapy is effective in decreasing transfusions to varying degrees in preterm infants. Recent animal studies using erythropoietin doses to achieve serum concentrations > 1000 mU/mL report neuroprotective effects. We evaluated the relationship between erythropoietin concentrations and neurodevelopmental outcome in extremely low birth weight infants.\n Preterm infants who weighed < or = 1000 g at birth were randomly assigned to erythropoietin (400 U/kg 3 times per week) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Peak serum erythropoietin concentrations were obtained every 2 weeks. Follow-up evaluation included anthropometric measurements, Bayley scales of mental and psychomotor development, neurologic examination, and determination of overall neurodevelopmental impairment. Data were collected at 18 to 22 months' corrected age by certified examiners who were masked to the treatment group. Analyses were performed to identify correlations between erythropoietin concentrations and outcomes.\n Sixteen extremely low birth weight infants were enrolled; 1 infant died at 2 weeks (placebo/control), and 15 had erythropoietin concentrations measured (7 erythropoietin, 8 placebo/control). Peak erythropoietin concentrations were significantly different between groups during the study (erythropoietin: 2027 +/- 1464 mU/mL; placebo/control: 26 +/- 11 mU/mL). Before follow-up, 3 infants died (1 erythropoietin, 2 placebo/control), and 12 were available for follow-up (6 erythropoietin, 6 placebo/control). At 18 to 22 months' follow-up, none of the erythropoietin recipients and 2 of the placebo/control infants had Mental Development Index scores < 70. Erythropoietin recipients had Mental Development Index scores of 96 +/- 11, and placebo/control infants had Mental Development Index scores of 78 +/- 7. Psychomotor Development Index scores were similar between groups (87 +/- 13 vs 80 +/- 7). There were no differences between groups with respect to anthropometric measurements. Two of 6 infants in the erythropoietin group and 4 of 6 infants in the placebo/control group had some form of neurodevelopmental impairment. Posthoc analysis showed that infants with erythropoietin concentrations > or = 500 mU/mL had higher Mental Development Index scores than infants with erythropoietin concentrations < 500 mU/mL.\n Erythropoietin concentrations did not correlate with Psychomotor Development Index or overall incidence of neurodevelopmental impairment; however, infants with elevated erythropoietin concentrations had higher Mental Development Index scores than those with lower erythropoietin concentrations. Close follow-up of infants who are enrolled in large, multicenter, high-dose erythropoietin studies is required to determine whether a correlation exists between elevated erythropoietin concentrations and improved neurodevelopmental outcome.", "Comparing a group of infants treated with recombinant erythropoietin and iron supplementation to a group of control infants, no difference was observed concerning the transfusion need. The incidence of retinopathy of prematurity was significantly higher in the treated group. These data need to be confirmed in randomized controlled studies.", "Early recombinant erythropoietin therapy and iron therapy would decrease the need for red blood cells transfusions and prevents anemia of prematurity.\n Fifty-eight preterm infants in newborn services at Ghaem Medical Center randomly were assigned, among them 18 patients were excluded. A total of 40 preterm infants with gestational age 28-34 weeks, birth weight 1000-1750 g followed the study: 20 infants in treatment group and 20 infants in control group were randomized to treatment (rhu EPO, 500u per kg, per week, 2 times weekly, subcutaneous) and control (no treatment). Therapy was initiated 4 days after birth and continued throughout the 4 weeks. All infants on enteral feeds received supplements: iron 3 mg/kg/d, vitamins and folat. Complete blood cells and reticulocyte counts were measured weekly. Transfusions and phlebotomy data were recorded. Statistical significance was determined by chi-square test, student t test and Mann-Whitney. A P value of < 0.05 was considered statistically significant.\n The reticulocyte counts were higher in treated infants during the study (p: 0.009). Final hematocrits were higher in treated infants (p: 0.02).The volume of packed red blood cells transfusions mililiter per infant significantly reduced (p: 0.05), the average number of transfusion per infant was also lower for treated infant than control [2 (10 % )vs 8 (40%) respectively]. No adverse effects of EPO or supplemental iron occurred.\n The combination of early rhu EPO and iron as administered in the present study stimulated erythropoiesis and decreased red blood cells transfusion in premature infants who were 1000-1750 g at birth. The enrollments of the larger and healthier preterm infants, who are at lower risk for transfusion, are limitation of the present study.", "The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources.", "To study the efficacy, safety and cost effectiveness of recombinant human erythropoietin (r-HuEPO) in reducing erythrocyte transfusion needs in very low birthweight (VLBW) infants.\n We conducted a non-blind randomized controlled trial and assigned 100 VLBW infants, less than 33 weeks gestation, to receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or no erythropoietin (EPO). Infants received oral iron 3-6 mg/kg per day from day 10. Transfusion needs were analysed for all enrolled infants and in five weight subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and infants more than 1200 g.\n VLBW infants on r-HuEPO attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different. Of infants 800-999 g at birth, the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant (P = 0.04). Volume of erythrocytes transfused was 34.9 +/- 32.1 mL/kg in r-HuEPO-treated infants and 56.6 +/- 25.8 mL/kg in control infants (P = 0.03). The cost per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for control infant. Blood pressure, neutrophil count, platelet count and complications of prematurity were not significantly different in both groups of VLBW infants.\n r-HuEPO at 750 U/kg per week stimulates erythropoiesis in VLBW infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800-999 g at birth." ]

[ "10948819", "9873176", "9762826", "8186137", "11499332", "2689014", "2229529", "16623023", "3430295" ]

[ "Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebo-controlled, double-blind study.", "Efficacy and safety of short-term itraconazole in tinea pedis: a double-blind, randomized, placebo-controlled trial.", "A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis.", "Two-week oral treatment of tinea pedis, comparing terbinafine (250 mg/day) with itraconazole (100 mg/day): a double-blind, multicentre study.", "Short-duration oral terbinafine for the treatment of tinea pedis in HIV-positive patients.", "Successful treatment of chronic tinea pedis (moccasin type) with terbinafine (Lamisil).", "Oral terbinafine versus griseofulvin in the treatment of moccasin-type tinea pedis.", "A comparison of the efficacy between two itraconazole generic products and the innovative itraconazole in the treatment of tinea pedis.", "Comparison of ketoconazole and griseofulvin in the treatment of tinea pedis." ]

[ "A clinical study was conducted to evaluate the effectiveness of lactoferrin, which is a protein component of cow's milk, in the treatment of tinea pedis. Doses of either 600 mg or 2000 mg of lactoferrin, or a placebo was orally administered daily for 8 weeks to 37 adults who were judged to have mild or moderate tinea pedis. Dermatological improvement and antifungal efficacy were assessed. In the analysis of all subjects, dermatological symptoms scores in all groups decreased but the differences were not statistically significant comparing the three groups. However, in the analysis limited to subjects with moderate vesicular or interdigital tinea pedis, dermatological symptoms scores in the lactoferrin-treated groups decreased significantly in comparison with the placebo group (P < 0.05). The organisms isolated were Trichophyton rubrum and Trichophyton mentagrophytes. A mycological cure was not seen in any of the subjects. In the 37 subjects there were no adverse events and no subject withdrew from the study because of an adverse event. These results suggest that orally administered lactoferrin can improve the dermatological symptoms in some subjects. The potential usefulness of lactoferrin as a functional food material for treating tinea pedis was seen for the first time in this study.", "Treatment of plantar or moccasin-type tinea pedis with conventional oral antifungal agents produces poor response rates. Itraconazole is a synthetic, broad-spectrum, orally active antifungal agent with pronounced antimycotic activity.\n To confirm the efficacy and safety of short-term treatment with itraconazole for plantar or moccasin-type tinea pedis.\n The study was a double-blind, randomized, placebo-controlled, multicenter trial. Seventy-two patients with tinea pedis (plantar or moccasin-type) were treated with itraconazole (200 mg twice daily) or placebo for 1 week with an 8-week treatment-free follow-up period.\n Thirty-six patients were randomized to each treatment group. The overall success rate (mycological cure and clinical response) at the end-point of follow-up was significantly higher in the itraconazole group than in the placebo group (53 vs. 3%; p <0. 001). Mycological cure (56 vs. 8%; p <0.001) and clinical response rates (75 vs. 11%; p <0.001) were significantly higher after itraconazole treatment compared with placebo treatment. During treatment, adverse events were recorded in 7 patients in the itraconazole group and 2 patients in the placebo group. Adverse events were noted in 3 patients in the placebo group during follow-up. No serious adverse events were reported in either group.\n Short-term treatment with itraconazole was significantly more effective than placebo in tinea pedis. The safety and tolerability profile or itraconazole was comparable with placebo.", "nan", "In this randomized double-blind trial, two new antifungal compounds were compared in patients with interdigital or more extensive forms of tinea pedis. Two weeks of oral treatment with either terbinafine, an allylamine and new chemical entity, 250 mg daily, or itraconazole 100 mg daily, was given to 366 patients (184 terbinafine, 182 itraconazole). Of 13 patients who did not return after the first visit, 11 were lost to follow-up (five on terbinafine, six on itraconazole) and two reported adverse events. Another nine patients (three on terbinafine and six on itraconazole) were excluded because it was uncertain to which group they were randomized. A central laboratory performed both the mycology and safety tests. In 355 patients who received the study medications and were available for analysis of side-effects, 18 out of 179 (10.0%) in the terbinafine group and 10 out of 176 (5.7%) in the itraconazole group reported adverse events. No new clinically significant laboratory abnormalities were seen after treatment. At week 8 the efficacy analysis in 117 patients with mycologically confirmed dermatophyte infections (51 on terbinafine, 66 on itraconazole) showed that clinical symptoms were absent or minimal in 94.1% of the terbinafine and 72.7% of the itraconazole group (P = 0.0095); mycology was negative in 86.3% of the terbinafine and 54.5% of the itraconazole group (P = 0.0002). With terbinafine, negative mycology at week 8 was 81.3% in the interdigital and 88.6% in the more extensive forms of tinea pedis; with itraconazole mycology was negative in 65.0% and 50.0% of patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "Management of tinea pedis in patients who have the human immunodeficiency virus (HIV) is problematic; in those patients, dermatophytoses may be more difficult to treat than in the general population. This prospective, open-label, multicenter, randomized study evaluated the efficacy and safety of a short course of oral terbinafine for tinea pedis in patients who are HIV positive. Twenty-seven patients were randomized to receive oral terbinafine 250 mg once daily for 2 or 4 weeks; 17 patients with positive initial cultures and follow-up cultures were evaluable for efficacy at week 8. Mycological cure (defined as negative potassium hydroxide [KOH] microscopy and culture results) occurred in 47% (8) of patients; and modified mycological cure (defined as negative follow-up cultures) occurred in 65% (11) of patients. All 27 patients were evaluated for safety. Clinical cure (defined as minimal residual signs and symptoms) occurred in 82% (14) of patients. Oral terbinafine was well tolerated, indicating that regimens of 2 or 4 weeks are safe and effective for the treatment of tinea pedis in patients who are HIV positive.", "Terbinafine (Lamisil) is the first safe and effective orally active agent in a new family of antifungal drugs, the allylamines. The drug has a unique site of action on sterol synthesis due to its inhibition of squalene epoxidase. The drug is highly effective against dermatophytes in vitro, and in placebo controlled trials, it is effective both topically and orally against dermatophytes. In the study reported here, terbinafine has been compared to griseofulvin in patients with moccasin type tinea pedis. Terbinafine was given at 125 mg b.i.d. and griseofulvin was given at 250 mg (microsize) b.i.d. Thirty-six patients were enrolled in a randomized, double-blind study. Patients were evaluated weekly by mycological culture, microscopy and clinical signs and symptoms for 6 weeks during therapy and at follow-up 2 weeks later. Twenty-eight of the 36 patients were evaluable for drug efficacy. Twelve out of sixteen (75%) of the terbinafine group were mycologically and clinically cured by the end of therapy (6 weeks) and 14/16 (88%) were cured at the time of follow-up 2 weeks later. Two patients were mycologically cured, but moderate signs or symptoms were present at follow-up. In the griseofulvin-treated group 3/12 (27%) were cured at the end of treatment and 5/11 (45%) at follow-up evaluation. Follow-up after 6-15 months showed continued resolution of the terbinafine-treated patients, but relapse of infection in griseofulvin-treated patients. There were two side-effects during terbinafine treatment (one gastro-intestinal, one skin allergy), and no significant changes in haematological, hepatic enzyme or renal blood tests done weekly.(ABSTRACT TRUNCATED AT 250 WORDS)", "The safety and effectiveness of oral terbinafine, 125 mg twice daily, and griseofulvin, 250 mg twice daily, in patients with moccasin-type tinea pedis were examined in a double-blind randomized trial. At the end of the 6-week treatment period, both a clinical and mycologic cure or a mycologic cure with minimal signs of infection was noted in 12 (75%) of the 16 terbinafine-treated patients compared with only 3 (27%) of the 12 patients treated with griseofulvin. The overall response rate 2 weeks after the completion of treatment was 88% in the terbinafine-treated group and 45% in the griseofulvin-treated group. When contacted again 6 to 15 months after completion of the study, 94% of the terbinafine-treated patients reported sustained clearing of tinea pedis, and 88% of those with nail involvement at the time of treatment reported improvement. In contrast, tinea pedis remained cured in only 30% of the patients who had received griseofulvin, and onychomycosis improved in only 14%.", "Treatment of tinea pedis with conventional oral antifungal agents produces poor response rates. Itraconazole is a broad-spectrum, orally active antifungal agent with pronounced antimycotic activity. However treatment cost of itraconazole is problematical in developing countries.\n To study the efficacy of the 1-pulse dosing regimen of two generic products of itraconazole (Itracon and Itra) in comparison with the innovative product (Sporal) for the treatment of tinea pedis.\n The study was a double-blind randomized controlled trial. One hundred and thirty-three patients with tinea pedis were treated with Itracon, Itra or Sporal 200 mg twice daily for 1 week. Clinical and mycological examinations were performed at baseline and at the follow-up visits (taking place at 1, 2, 4 and 12 weeks after the medication administration).\n Fifty-four, sixty-one and eighteen patients were randomized to Sporal, Itracon and Itra treatment group respectively. Mycological cure rate and clinical response rates were not significantly different among the three groups. Moreover there were also no statistically significant differences with regard to relapse rate. During treatment, no serious adverse events were recorded in any groups.\n The present study demonstrated that the efficacy of the original and generic itraconazole is not significantly different in the treatment of tinea pedis by the pulse regimen.", "Twenty-nine patients with mycologically proven tinea pedis were randomly allocated to oral treatment with either ketoconazole 200 mg daily or griseofulvin 1 g daily for a period of up to 8 weeks. Mycological cure rate at 4 weeks was 33% for ketoconazole and 29% for griseofulvin, and at 8 weeks was 53% and 57% respectively. The efficacy of both drugs in the treatment of interdigital tinea pedis is similar, and is considerably lower than that found with topical imidazole preparations where cure rates of over 70% are generally expected." ]

[ "15625442", "11226652" ]

[ "Early enteral nutrition does not decrease hypermetabolism associated with burn injury.", "Effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients." ]

[ "A prospective, randomized study was performed to compare the effects of early versus late enteral feeding on postburn metabolism.\n Burn patients were randomized to receive enteral feedings either within 24 hours (early) or 7 days (late) of injury. Basal energy expenditure (BEE) was calculated from Harris-Benedict equations and resting energy expenditure (REE) was obtained from indirect calorimetry. The average daily energy expenditure (DEE) was expressed as REE/BEE.\n Average age, burn size, infections, and length of stay were similar between groups. Mortality between groups was similar (early, 28%; late, 38%) and not significantly influenced by inhalation injury. When controlled for percentage of total body surface area burn, inhalation injury, and age, the early group had an increased rather than decreased DEE, with a mean DEE calorie 0.17 more than the late group (p = 0.07).\n Early enteral feeding does not decrease the average energy expenditure associated with burn injury.", "The aim of the study was to analyse the effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients. A total of 22 patients with severe burns were randomly divided into an early enteral feeding group (EF) and a delayed enteral feeding group (DF). The levels of serum endotoxin and TNF-alpha were dynamically detected in the members of both groups, and two unmetabolized sugars (lactulose and mannitol) were orally administered to these patients 1, 3 and 5 days postburn. Intestinal permeability was evaluated by detecting the concentrations of lactulose and mannitol in the urine and the lactulose-mannitol ratio (L/M) ratio. The levels of serum endotoxin and TNF-alpha in severely burned patients were significantly higher than in normal subjects (P<0.01). The endotoxin level was positively related to the TNF-alpha level (rEF=0.93, P<0.01; rDF=0.80, P<0.05). The urinary lactulose levels in both groups were significantly higher than in normal (P<0.01), the urinary mannitol levels showed no obvious changes (P>0.05). The urinary L/M ratios in both groups were significantly higher than in normal subjects (P<0.01). The urinary L/M ratio was positively related to the serum endotoxin level (r=0.95, P<0.01). The urinary lactulose levels and the urinary L/M ratios in the EF group were significantly lower than in the DF group (P<0.01). The levels of serum endotoxin and TNF-alpha in the EF group were significantly lower than in the DF group (P<0.01). It is suggested that intestinal permeability was markedly higher after burns than normal, and was positively related to the gut-derived endotoxemia. Early enteral feeding may decrease intestinal permeability, preserve the intestinal mucosal barrier and have a beneficial effect on the reduction of enterogenic infection." ]

[ "12566175", "10848721", "15800228", "12195763", "8987189", "20711135", "11014390", "20495588", "17182183", "12966259", "15254060", "18349204", "3911140", "19208440", "15983466", "18262450", "20496177", "19796802", "19962354" ]

[ "A randomised, double blind, placebo controlled crossover study of the cholecystokinin 2 antagonist L-365,260 as an adjunct to strong opioids in chronic human neuropathic pain.", "Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study.", "Morphine, gabapentin, or their combination for neuropathic pain.", "Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study.", "Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy.", "Combination of alpha lipoic acid and gabapentin, its efficacy in the treatment of Burning Mouth Syndrome: a randomized, double-blind, placebo controlled trial.", "Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.", "Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial.", "Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain.", "A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain.", "Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group.", "Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds.", "Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study.", "Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: a prospective double-blind randomized placebo-controlled study.", "Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial.", "Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients.", "A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA.", "Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial.", "A randomized, controlled trial of oxycodone versus placebo in patients with postherpetic neuralgia and painful diabetic neuropathy treated with pregabalin." ]

[ "The aim of this study was to establish if the cholecystokinin (CCK) 2 antagonist L-365,260 augments the analgesic effect of morphine in human subjects with chronic neuropathic pain. This is a randomised, double blind, placebo controlled study of 40 adult subjects taking morphine for neuropathic pain. Each received placebo, L-365,260 30 mg and L-365,260 120 mg in three divided doses daily separated by a washout period in random order. Pain, activity, sedation, sleep and side effects were recorded along with 12 lead ECGs, renal and liver function tests and full blood pictures. L-365,260 failed to augment the analgesic effect of morphine at any of the dose levels used. Side effects were minor. There were no changes in ECGs and biochemical indices were unaltered with its use. The CCK 2 antagonist L-365,260 does not augment the analgesic effect of morphine in subjects with chronic neuropathic pain. L-365,260 was well tolerated and side effects from its use were minor.", "To assess the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin and a combination of 3. 3% doxepin and 0.025% capsaicin in human chronic neuropathic pain.\n A randomized, double-blind, placebo-controlled study of 200 consenting adult patients. Patients applied placebo, doxepin, capsaicin or doxepin/capsaicin cream daily for 4 weeks. Patients recorded on a daily basis overall pain, shooting, burning, paraesthesia and numbness using a 0-10 visual analogue scale during the week prior to cream application (baseline levels) and for the 4 week study period. Side-effects and desire to continue treatment were also recorded.\n Overall pain was significantly reduced by doxepin, capsaicin and doxepin/capsaicin to a similar extent. The analgesia with doxepin/capsaicin was of more rapid onset. Capsaicin significantly reduced sensitivity and shooting pain. Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin. Side-effects were minor. One patient requested to continue placebo cream, 17 doxepin cream, 13 capsaicin and 9 the combination of doxepin and capsaicin.\n Topical application of 3.3% doxepin, 0.025% capsaicin and 3.3% doxepin/0. 025% capsaicin produces analgesia of similar magnitude. The combination produces more rapid analgesia.", "The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia.\n In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine--each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and quality of life.\n Of 57 patients who underwent randomization (35 with diabetic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Mean daily pain (on a scale from 0 to 10, with higher numbers indicating more severe pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at baseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P<0.05) with the combination than for each drug as single agent. At the maximal tolerated dose, the gabapentin-morphine combination resulted in a higher frequency of constipation than gabapentin alone (P<0.05) and a higher frequency of dry mouth than morphine alone (P<0.05).\n Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.\n Copyright 2005 Massachusetts Medical Society.", "Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain.\n Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded.\n No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects.\n In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.", "We compared the efficacy and tolerance of the combination of nortriptyline-fluphenazine (NF) vs. carbamazepine (CMZ) in the symptomatic therapy of patients with severe, distal, symmetrical, predominantly sensitive diabetic polyneuropathy (DPN). We followed a double blind, crossover, randomized and double placebo design. Sixteen patients with severe DPN participated in the study. Patients received either NF (1 tablet three times a day (tid)), for 2 weeks and 2 tablets tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for the next 2 weeks. After this, patients received placebos of both drugs (wash-out period), until symptoms returned to baseline levels (100%), then they were crossed over to receive the other comparing drug schedule. A visual analogue scale was used to evaluate the percent changes in pain and paresthesia. HbA1, fasting serum glucose, and safety tests were performed at 2- and 4-week intervals, respectively. Both therapies produced significant improvement of both pain and paresthesia. No statistically significant differences were observed between both therapies for either pain or paresthesia. No significant biochemical changes were observed with any of the two therapies. Side effects were mild and more frequent in the NF period. In this study no superiority of either drug schedule was demonstrated; therefore, the decision to use any of them should be made according to the associated pathology and potential side effects of each drug.", "Burning Mouth Syndrome (BMS) is a disease that manifests as burning in the tongue or in any area of the oral mucosa, in the absence of clinically verifiable injuries.\n To verify the efficacy of alpha lipoic acid (ALA) and gabapentin (GABA), used individually and jointly, to reduce the burning in patients with burning mouth and establish a drug therapy for the BMS.\n During April and May 2008, we conducted a randomized, double-blind, placebo-controlled trial in the Department of Clinical Stomatology, Faculty of Dentistry, Rosario, Argentina. The gathering of patients was between those ones with BMS who were treated in our service between March 2003 and March 2008 without complying with the applied treatments. The 120 patients were randomly divided into 4 groups and were provided, by lot and in a blinded fashion, with four different treatment cycles consisting of the following drugs: Group A (n = 20) 600 mg / day of alpha lipoic acid for two months, Group B (n = 20) 300 mg / day of gabapentin for two months, Group C (n = 20) a combination of both drugs for two months and Group D (n = 60) 100 mg / day of cellulose starch for two months (control group).\n all 120 patients completed the treatment. The best response was obtained with the combination of ALA + GABA, with a 70% of the cases with reduced burning in this group and a 13.2 times greater chance of presenting positive changes for these patients than those taking placebo. The combined use of drugs that act at different levels of the nociceptive system can be useful for the treatment of this syndrome.", "Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case.\n In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale.\n A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline.\n These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine.", "Severe, intractable, chronic pain is a significant management problem for those involved in the long-term care of spinal cord injury (SCI) patients . Gabapentin, an anticonvulsant, is widely used for treating chronic pain. Ketamine, an NMDA receptor antagonist, has been available in clinical practice for 35 years. Its usefulness in pathological pain states is known. Despite this, no formal research on its effectiveness in treating neuropathic SCI pain exists.\n This double-blind study sought to determine the safety and efficacy of adding a multi-day low dose ketamine infusion to oral gabapentin for treating chronic pain related to post spinal cord injury.\n Randomized, controlled, double blind trial.\n Hospital, in-patient setting.\n Forty patients diagnosed with neuropathic pain secondary to spinal cord injury were randomized into 2 equal groups. Group I received an 80 mg intravenous ketamine infusion diluted in 500 cc normal saline over a 5 hour period daily for one week and 300 mg of gabapentin 3 times daily. Group II received a placebo infusion and 300 mg of gabapentin 3 times daily (continued) after 300 mg of gabapentin 3 times daily. Using the visual analogue scale, pain was assessed prior to treatment, daily following ketamine or placebo infusions for 7 days, and then weekly for one month after infusion termination. Side effects, specifically those related to ketamine or gabapentin, were reported.\n Both groups demonstrated significantly reduced pain scores compared with pre-treatment values (P < 0.05). Group I showed significant pain score improvements over Group II at all measurements (P < 0.0001) during infusion and 2 weeks after infusion termination. There was no statistical difference between the groups at 3 weeks and 4 weeks after infusion termination (P = 0.54 and P = 0.25 respectively). Both drugs were tolerated by all patients; no side effects required intervention.\n Multi-day low dose ketamine infusion as adjuvant to gabapentin in post-spinal cord injury related chronic pain is safe and efficacious in reducing pain, but the effect compared to placebo ceased 2 weeks after infusion termination.\n Study size limited to 40 patients.", "Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine \"active placebo\" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0-10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI=[-2%, 30%]), 7% for morphine (95% CI=[-8%, 22%]), and 7% for the combination treatment (95% CI=[-4%, 18%]). Mean doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29 mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/-33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.", "The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain.\n The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred.\n There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream.\n This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial.", "To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain.\n One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opioid analgesics.\n Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%).\n Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.", "Calcitonin was effective in a study of acute phantom limb pain, but it was not studied in the chronic phase. The overall literature on N-methyl-D-aspartate antagonists is equivocal. We tested the hypothesis that calcitonin, ketamine, and their combination are effective in treating chronic phantom limb pain. Our secondary aim was to improve our understanding of the mechanisms of action of the investigated drugs using quantitative sensory testing.\n Twenty patients received, in a randomized, double-blind, crossover manner, 4 i.v. infusions of: 200 IE calcitonin; ketamine 0.4 mg/kg (only 10 patients); 200 IE of calcitonin combined with ketamine 0.4 mg/kg; placebo, 0.9% saline. Intensity of phantom pain (visual analog scale) was recorded before, during, at the end, and the 48 h after each infusion. Pain thresholds after electrical, thermal, and pressure stimulation were recorded before and during each infusion.\n Ketamine, but not calcitonin, reduced phantom limb pain. The combination was not superior to ketamine alone. There was no difference in basal pain thresholds between the amputated and contralateral side except for pressure pain. Pain thresholds were unaffected by calcitonin. The analgesic effect of the combination of calcitonin and ketamine was associated with a significant increase in electrical thresholds, but with no change in pressure and heat thresholds.\n Our results question the usefulness of calcitonin in chronic phantom limb pain and stress the potential interest of N-methyl-D-aspartate antagonists. Sensory assessments indicated that peripheral mechanisms are unlikely important determinants of phantom limb pain. Ketamine, but not calcitonin, affects central sensitization processes that are probably involved in the pathophysiology of phantom limb pain.", "A controlled clinical trial on the efficacy of a nortriptyline-fluphenazine combination was carried out in patients with painful diabetic polyneuropathy. A visual analog scale was used to evaluate the relief of pain or paresthesia. Significant relief of both pain and paresthesia was obtained with this combination. The differences were statistically significant. Side effects were frequent but not usually severe enough to lead to cessation of these medications.", "Combination of drugs with different mechanisms of action helps in achieving synergistic analgesic effect in neuropathic pain. Keeping this point in view, the effect and safety aspects of sodium valproate and GTN were assessed alone as well as in combination in this study.\n Prospective double-blind randomized placebo-controlled study.\n Eighty-seven type 2 diabetics with painful neuropathy were enrolled. Four were excluded: three with HbA1c>11 while one withdrew consent. The remaining 83 were given either sodium valproate and GTN spray (group A) or placebo drug and GTN spray (group B) or sodium valproate and placebo spray (group C) or placebo drug and placebo spray (group D). Quantitative assessment of pain was done by McGill pain questionnaire, visual analogue score (VAS) and present pain intensity (PPI) at the beginning of the study and after 3 months along with motor and sensory nerve conduction velocities measurements.\n All the three treatment groups experienced significant improvement in pain score in their drug phase of trial (p<0.001/<0.05) along with some of the electrophysiological parameters. The assessment of the magnitude of therapeutic effect of sodium valproate, GTN and their combination gave numbers needed to treat (NNT) of 7, 5 and 4, respectively.\n Sodium valproate and GTN are well tolerated and provide significant improvement in pain scores as well as in electrophysiological parameters.", "A double-blind, randomized, placebo-controlled 3-week study evaluated the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both in treating patients with neuropathic pain.\n Ninety-two patients with diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic neuropathic pain with allodynia, hyperalgesia, or pinprick hypesthesia were randomly assigned to receive one of four creams (placebo, 2% amitriptyline, 1% ketamine, or 2% amitriptyline-1% ketamine combined). The primary outcome measure was change in average daily pain intensity (baseline week vs. final week) using an 11-point numerical pain rating scale. Secondary outcomes included the McGill Pain Questionnaire, measures of allodynia and hyperalgesia, and patient satisfaction.\n A reduction in pain scores of 1.1-1.5 units was observed in all groups, and there was no difference between groups. Blood concentrations revealed no significant systemic absorption. Minimal side effects were encountered.\n This randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination in the treatment of neuropathic pain revealed no difference between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia.", "Neuropathic pain remains one of the most challenging pain syndromes; under-diagnosed, poorly managed and associated with significant co-morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose-related adverse events.\n This randomized, double-blind, placebo-controlled study assessed the potential benefit of adding oxycodone (OxyContin tablets) to gabapentin. The primary endpoint was to evaluate the analgesic efficacy of co-administration of gabapentin and prolonged-release oxycodone, whilst also evaluating the use of escape medication, sleep quality and global assessment of pain.\n Three hundred and thirty eight patients with moderate to severe painful diabetic neuropathy despite receiving their maximum tolerated dose of gabapentin, had oral prolonged-release oxycodone or placebo tablets added to their therapy for up to 12 weeks.\n Oxycodone-gabapentin reduced pain score by 33% from baseline to end of treatment. The overall treatment effect was greater with oxycodone-gabapentin than with placebo-gabapentin (P = 0.007). Oxycodone-gabapentin also significantly improved pain relief vs gabapentin alone (P = 0.003). Oxycodone-gabapentin co-administration was associated with less escape medication use (P = 0.03) and fewer nights of disturbed sleep (P < 0.05). Discontinuations due to lack of therapeutic effect were much lower (14% vs 54%) with oxycodone-gabapentin. The commonly seen opiate-induced adverse events were not exacerbated by the combination of oxycodone and gabapentin.\n This study provides the first evidence that co-administration of prolonged-release oxycodone and existing gabapentin therapy has a clinically meaningful effect in painful diabetic neuropathy.", "Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem.\n Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks.\n Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p = 0.053) and motor subscales (p = 0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity.\n Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN.", "Drugs for neuropathic pain have incomplete efficacy and dose-limiting side-effects when given as monotherapy. We assessed the efficacy and tolerability of combined nortriptyline and gabapentin compared with each drug given alone.\n In this double-blind, double-dummy, crossover trial, patients with diabetic polyneuropathy or postherpetic neuralgia, and who had a daily pain score of at least 4 (scale 0-10), were enrolled and treated at one study site in Canada between Nov 5, 2004, and Dec 13, 2007. 56 patients were randomised in a 1:1:1 ratio with a balanced Latin square design to receive one of three sequences of daily oral gabapentin, nortriptyline, and their combination. In sequence, a different drug was given to each randomised group in three treatment periods. During each 6-week treatment period, drug doses were titrated towards maximum tolerated dose. The primary outcome was mean daily pain at maximum tolerated dose. Analysis was by intention to treat. This trial is registered, number ISRCTN73178636.\n 45 patients completed all three treatment periods; 47 patients completed at least two treatment periods and were analysed for the primary outcome. Mean daily pain (0-10; numerical rating scale) was 5.4 (95% CI 5.0 to 5.8) at baseline, and at maximum tolerated dose, pain was 3.2 (2.5 to 3.8) for gabapentin, 2.9 (2.4 to 3.4) for nortriptyline, and 2.3 (1.8 to 2.8) for combination treatment. Pain with combination treatment was significantly lower than with gabapentin (-0.9, 95% CI -1.4 to -0.3, p=0.001) or nortriptyline alone (-0.6, 95% CI -1.1 to -0.1, p=0.02). At maximum tolerated dose, the most common adverse event was dry mouth, which was significantly less frequent in patients on gabapentin than on nortriptyline (p<0.0001) or combination treatment (p<0.0001). No serious adverse events were recorded for any patients during the trial.\n Combined gabapentin and nortriptyline seems to be more efficacious than either drug given alone for neuropathic pain, therefore we recommend use of this combination in patients who show a partial response to either drug given alone and seek additional pain relief. Future trials should compare other combinations to their respective monotherapies for treatment of such pain.\n Canadian Institutes of Health Research.", "The aim of this randomized double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of pregabalin in combination with oxycodone or placebo, in patients with either postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN). After a 7-day washout period, 62 patients were randomized to receive either oxycodone mixture 10 mg/day or placebo mixture for 1 week. Patients were then started on open-label pregabalin (75, 150, 300 and 600 mg/day) according to a forced titration dosing regimen, while continuing the same dosage of oxycodone or placebo for 4 weeks. The primary efficacy measure was a decrease in the pain-intensity score of at least 2cm and a pain score <4cm measured using a 10-cm visual analogue scale (VAS) following pregabalin dosage escalation and treatment for 4 weeks. Secondary efficacy measures included sleep interference and the Neuropathic Pain Scale. There were similar levels of overall efficacy between pregabalin/oxycodone and pregabalin/placebo groups in relieving PHN and PDN related pain.\n Peripheral neuropathic pain presents commonly in clinical practice, and 2 of its most prevalent types are PHN and PDN. Currently available treatments provide some degree of pain relief in approximately 40-60% of patients, leaving the remainder with unremitting pain. Although this study supports the effectiveness of pregabalin in the treatment of PHN or PDN, it also shows that the addition of a low dose of oxycodone at 10mg/day does not enhance the pain-relieving effects of pregabalin.\n Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved." ]

[ "1609377", "8757209", "3106448" ]

[ "Auranofin in the treatment of steroid dependent asthma: a double blind study.", "A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. Auranofin Multicenter Drug Trial.", "Chrysotherapy in the treatment of corticosteroid-dependent asthma." ]

[ "Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti-inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated.\n A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids.\n Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable.\n Auranofin provides an effective adjunct to treatment for steroid dependent asthma, leading to a reduction of oral steroid dose.", "Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma.\n The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma.\n Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring > or = 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase I), a 6-month double-blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was \"therapeutic success\" or reduction of daily corticosteroid use by 50% or more.\n The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p < 0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (> or = 50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p < 0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group.\n Auranofin demonstrated a steroid-sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid-dependent asthma.", "The efficacy of parenteral gold therapy was evaluated in patients with steroid-dependent asthma. Five of eight patients improved in terms of reduced steroid requirement while they were maintaining or improving lung function. Two patients developed significant proteinuria that resolved with cessation of gold. Chrysotherapy appears to have a corticosteroid-sparing effect in some patients and may have a useful role in the management of severe refractory asthma." ]

[ "4011073", "8518240" ]

[ "Prospective randomized study of x-ray pelvimetry in the primigravida.", "Vaginal delivery after previous caesarean section: is X-ray pelvimetry necessary?" ]

[ "A prospective randomized study was performed to determine the usefulness of x-ray pelvimetry before oxytocin induction or augmentation. Two hundred primiparous women were entered into this study. Agreement on pelvic size by the clinical and radiologic assessment occurred in 76.5% of the cases. When the total groups were compared, there were no differences in pregnancy outcome. In the induction of labor subgroups there were less forcep deliveries and lower five-minute Apgar scores in the pelvimetry group. In the augmentation subgroups there were no differences. The subgroup of patients diagnosed clinically to have a borderline pelvis, had a higher incidence of cesarean section (P less than .05) if they had x-ray pelvimetry. These results suggest that the elimination of x-ray pelvimetry in primigravida women does not lead to a compromise in infant outcome when electronic fetal monitoring is used.", "To determine whether antepartum X-ray pelvimetry (XRP) reliably identified women suitable for a trial labour or repeat elective caesarean section after one previous section.\n A prospective controlled trial in which women were randomly allocated to either an antepartum XRP group who had XRP at 36 weeks gestation to determine mode of delivery, or a control group who had a trial labour without antepartum XRP. Following delivery, all controls had postpartum XRP.\n Department of Obstetrics and Gynaecology, King Edward VIII Hospital, Durban, South Africa.\n Three hundred-six women with a history of one previous caesarean section.\n Mode of delivery, birthweight and maternal and perinatal mortality and morbidity in the two groups.\n In the antepartum XRP group, 23 of 144 (16%) of women delivered vaginally compared with 60 of 144 (42%) controls (P < 0.0001). Of the 84 women with adequate antepartum XRP only 23 (27.7%) delivered vaginally. In the control group, 33 of 60 (55%) women who had vaginal deliveries had inadequate postpartum XRP and would have had a caesarean section if this information was known in the antepartum period; 62 of 84 (74%) caesarean sections in the control group had adequate postpartum XRP. Birthweight of the infants was similar in the two groups. There were no maternal or perinatal deaths. Maternal morbidity was similar in the two groups. Neonatal morbidity was minimal.\n Antepartum XRP is not necessary prior to a trial labour in women with one previous caesarean section. It increases the caesarean section rate and is a poor predictor of the outcome of labour." ]

[ "17043536", "2520394", "18312661", "18496246", "12428824", "12691335", "10729968", "14629842", "17303443", "6351130", "8523357", "15836978", "15626162" ]

[ "Does transcutaneous electrical nerve stimulation improve the physical performance of people with knee osteoarthritis?", "Randomized trial of Codetron for pain control in osteoarthritis of the hip/knee.", "A pilot study on using acupuncture and transcutaneous electrical nerve stimulation (TENS) to treat knee osteoarthritis (OA).", "Comparing hot pack, short-wave diathermy, ultrasound, and TENS on isokinetic strength, pain, and functional status of women with osteoarthritic knees: a single-blind, randomized, controlled trial.", "Does four weeks of TENS and/or isometric exercise produce cumulative reduction of osteoarthritic knee pain?", "Optimal stimulation duration of tens in the management of osteoarthritic knee pain.", "TENS, electroacupuncture and ice massage: comparison of treatment for osteoarthritis of the knee.", "The effects of electro-acupuncture and transcutaneous electrical nerve stimulation on patients with painful osteoarthritic knees: a randomized controlled trial with follow-up evaluation.", "A 3-month, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a highly optimized, capacitively coupled, pulsed electrical stimulator in patients with osteoarthritis of the knee.", "TNS and osteo-arthritic pain. Preliminary study to establish a controlled method of assessing transcutaneous nerve stimulation as a treatment for the pain caused by osteo-arthritis of the knee.", "The treatment of osteoarthritis of the knee with pulsed electrical stimulation.", "Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment.", "Optimal stimulation frequency of transcutaneous electrical nerve stimulation on people with knee osteoarthritis." ]

[ ": According to a recent metaanalysis study, there is strong evidence to support the view that transcutaneous electrical nerve stimulation (TENS) is an effective treatment for managing osteoarthritis (OA) knee pain. However, there is limited evidence showing its effectiveness in improving physical function. This study examined whether TENS alone can improve physical function in terms of range of knee motion and the Timed-Up-and-Go Test.\n : Subjects were randomly allocated into 2 groups receiving TENS at 100 Hz or a placebo TENS. Outcome measures included: 1) visual analog scale for measuring the intensity of the present pain, 2) Timed-Up-and-Go Test, and 3) range of knee motion (ROM). Repeated-measures analysis of variance and Pearson correlation were used for data analyses.\n : By day 10, TENS produced a significantly greater increase in maximum knee ROM than the placebo group (P = 0.033). TENS also significantly increased the pain-limited knee ROM across sessions, but the between-group difference was short of significance (P = 0.067). The decrease in time in performing the Timed-Up-and-Go Test was also not significantly different between the 2 groups. A moderate correlation was observed between the reduction in pain scores and the improvement in the Timed-Up-and-Go Test.\n : Our findings suggested that TENS did improve some of the physical parameters but over 10 days was unable to produce significant improvement in functional performance among people with knee OA. A larger-scale study with the assessment of other functional outcomes may be required to clarify if TENS could improve function in people with knee OA. Also, exercise can be considered to be an important adjunct treatment to TENS to improve function significantly.", "Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial, saphenous, popliteal and sciatic nerves, and tender points. Seventy-four percent of patients in the real Codetron (Group A) and 28% of the patients in sham Codetron (Group B) improved their pain level more than 25% as measured by visual analogue scale. The difference in pain improvement in the two groups was statistically significant (p less than 0.02 using Fisher's exact probability ratio). Other functional parameters proved to be insensitive to change in this study. This is highly suggestive of beneficial effect of nonhabituating Codetron as a complementary modality in the therapy of chronic pain conditions such as osteoarthritis.", "The present study tests whether a combined treatment of acupuncture and transcutaneous electrical nerve stimulation (TENS) is more effective than acupuncture or TENS alone for treating knee osteoarthritis (OA).\n Thirty-two patients with knee OA were randomly allocated to four groups. The acupuncture group (ACP) received only acupuncture treatment at selected acupoints for knee pain; the TENS group (TENS) received only TENS treatment at pain areas; the acupuncture and TENS group (A&T) received both acupuncture and TENS treatments; the control group (CT) received topical poultice (only when necessary). Each group received specific weekly treatment five times during the study. Outcome measures were pain intensity in a visual analogue scale (VAS) and knee function in terms of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).\n The ACP, TENS and A&T groups reported lower VAS and WOMAC scores than the control group. Significant reduction in pain intensity (P = 0.039) and significant improvement in knee function (P = 0.008) were shown in the A&T group.\n Combined acupuncture and TENS treatment was effective in pain relief and knee function improvement for the sampled patients suffering from knee OA.", "To investigate the therapeutic effects of physical agents administered before isokinetic exercise in women with knee osteoarthritis.\n One hundred patients with bilateral knee osteoarthritis were randomized into five groups of 20 patients each: group 1 received short-wave diathermy + hot packs and isokinetic exercise; group 2 received transcutaneous electrical nerve stimulation + hot packs and isokinetic exercise; group 3 received ultrasound + hot packs and isokinetic exercise; group 4 received hot packs and isokinetic exercise; and group 5 served as controls and received only isokinetic exercise.\n Pain and disability index scores were significantly reduced in each group. Patients in the study groups had significantly greater reductions in their visual analog scale scores and scores on the Lequesne index than did patients in the control group (group 5). They also showed greater increases than did controls in muscular strength at all angular velocities. In most parameters, improvements were greatest in groups 1 and 2 compared with groups 3 and 4.\n Using physical agents before isokinetic exercises in women with knee osteoarthritis leads to augmented exercise performance, reduced pain, and improved function. Hot pack with a transcutaneous electrical nerve stimulator or short-wave diathermy has the best outcome.", "To evaluate the cumulative effect of repeated transcutaneous electrical nerve stimulation (TENS) on chronic osteoarthritic (OA) knee pain over a four-week treatment period, comparing it to that of placebo stimulation and exercise training given alone or in combination with TENS.\n Sixty-two patients, aged 50-75, were stratified according to age, gender and body mass ratio before being randomly assigned to four groups.\n Patients received either (1) 60 minutes of TENS, (2) 60 minutes of placebo stimulation, (3) isometric exercise training, or (4) TENS and exercise (TENS & Ex) five days a week for four weeks.\n Visual analogue scale (VAS) was used to measure knee pain intensity before and after each treatment session over a four-week period, and at the four-week follow-up session.\n Repeated measures ANOVA showed a significant cumulative reduction in the VAS scores across the four treatment sessions (session 1, 10, 20 and the follow-up) in the TENS group (45.9% by session 20, p < 0.001) and the placebo group (43.3% by session 20, p = 0.034). However, linear regression of the daily recordings of the VAS indicated that the slope in the TENS group (slope = -2.415, r = 0.943) was similar to the exercise group (slope = -2.625, r = 0.935), which were steeper than the other two groups. Note that the reduction of OA knee pain was maintained in the TENS group and the TENS & Ex group at the four-week follow-up session, but not in the other two groups.\n The four treatment protocols did not show significant between-group difference over the study period. It was interesting to note that isometric exercise training of the quadriceps alone also reduced knee pain towards the end of the treatment period.", "This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation (TENS) for relieving osteoarthritic knee pain and the duration (as measured by half-life) of post-stimulation analgesia.\n Thirty-eight patients received either: (i) 20 minutes (TENS20); (ii) 40 minutes (TENS40); (iii) 60 minutes (TENS60) of TENS; or (iv) 60 minutes of placebo TENS (TENS(PL)) 5 days a week for 2 weeks.\n A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation.\n By Day10, a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 (83.40%) and TENS60 (68.37%) groups than in the TENS20 (54.59%) and TENS(PL) (6.14%) groups (p < 0.000), such a group difference was maintained in the 2-week follow-up session (p < 0.000). In terms of the duration of post-stimulation analgesia period, the duration for the TENS40 (256 minutes) and TENS60 (258 minutes) groups was more prolonged than in the other 2 groups (TENS20 = 168 minutes, TENS(PL) = 35 minutes) by Day10 (p < 0.000). However, the TENS40 group produced the longest pain relief period by the follow-up session.\n 40 minutes is the optimal treatment duration of TENS, in terms of both the magnitude (VAS scores) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis.", "The purpose of this study was to compare the effectiveness of transcutaneous nerve stimulation (TENS), electroacupuncture (EA), and ice massage with placebo treatment for the treatment of pain. Subjects (n = 100) diagnosed with osteoarthritis (OA) of the knee were treated with these modalities. The parameters for evaluating the effectiveness of treatment include pain at rest, stiffness, 50 foot walking time, quadriceps muscle strength, and knee flexion degree. The results showed (a) that all three methods could be effective in decreasing not only pain but also the objective parameters in a short period of time; and (b) that the treatment results in TENS, EA and ice massage were superior to placebo.", "To examine the relative effectiveness of electro-acupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) in alleviating osteoarthritic (OA)-induced knee pain.\n Single-blinded, randomized controlled study.\n Twenty-four (24) subjects (23 women and 1 man), mean age 85, were recruited from eight subsidized Care & Attention Homes for the elderly.\n Subjects were randomly assigned to the EA, TENS, or control groups. Subjects in the EA group (n = 8) received low-frequency EA (2 Hz) on two acupuncture points (ST-35, Dubi and EX-LE-4, Neixiyan) of the painful knee for 20 minutes. Subjects in the TENS group (n = 8) received low-frequency TENS of 2 Hz and pulse width of 200 micros on the same acupuncture points for 20 minutes. In both treatment groups, electrical treatment was carried out for a total of eight sessions in 2 weeks. Eight subjects received osteoarthritic knee care and education only in a control group. All subjects were evaluated before the first treatment, after the last treatment, and at 2-week follow-up periods.\n After eight sessions of treatment, there was significant reduction of knee pain in both EA group and TENS group, as measured by the Numeric Rating Scale (NRS) of pain (p < 0.01). Prolonged analgesic effect was maintained in the EA and the TENS groups at a 2-week follow-up evaluation. The Timed Up-and-Go Test (TUGT) score of the EA group was significantly lower than that of the control group (p < 0.05), but such change was not observed in the TENS group.\n Both EA and TENS treatments were effective in reducing OA-induced knee pain. EA had the additional advantage of enhancing the TUGT results as opposed to TENS treatment or no treatment, which did not produce such corollary effect.", "To investigate the efficacy and safety of a capacitively coupled, pulsed electrical stimulation device in treating knee osteoarthritis (OA).\n Fifty-eight outpatients with moderate to severe OA of the knee entered a 3-month, double-blind, placebo-controlled trial, using either an active or placebo device at home for 6 to 14 h/day. Outcome measures included a patient global evaluation, a patient report of knee pain severity, and the Western Ontario and McMaster Universities (WOMAC) questionnaire.\n Active treatment provided superior outcomes between baseline and 3-month follow-up measurements: 50.6% greater improvement than placebo in patient global (P=0.03), 31.2% in patient pain (P=0.04), 25.1% in WOMAC stiffness (P=0.03), 29.5% in WOMAC function (P=0.01), 19.9% in WOMAC pain (P=0.11), and 27% in total WOMAC (P=0.01). The percent of patients who improved by more than 50% was 38.5 active vs 5.3 placebo in patient global (P=0.01), 43.6 vs 15.8 in patient pain (P=0.04), 38.5 vs 10.5 in WOMAC pain (P=0.03), 28.2 vs 5.3 in WOMAC stiffness (P=0.08), 23.1 vs 5.3 in WOMAC function (P=0.14), and 23.1 vs 5.3 in total WOMAC (P=0.14). Twenty-one percent of placebo and 18% of actively treated patients developed a transient rash at the electrode sites. No other adverse device effects were reported.\n A highly optimized, capacitively coupled, pulsed electrical stimulus device significantly improved symptoms and function in knee OA without causing any serious side effects.", "nan", "The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee.\n A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period.\n Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time.\n The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.", "It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect, as suggested by the gate control theory. Electrical stimulation (by way of Interferential Current) applied at the pain area (segmental) was administered to 4 groups of patients with osteoarthritis (OA) knee pain. Two groups were administered with noxious stimulation (30% above pain threshold) and two with innocuous stimulation (30% below pain threshold). In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived. Group 5 and 6 received sham stimulation and no treatment, respectively. The outcome measures were: chronic pain intensity, morning stiffness, range of motion (ROM), pain threshold and % pain reduction. Both noxious and innocuous stimulation significantly decreased chronic pain (P<0.001) and morning stiffness (P<0.01) and significantly increased pain threshold (P<0.001) and ROM (P<0.001) compared with the control groups. Nevertheless, noxious stimulation decreased pain intensity (P<0.05) and increased pain threshold (P<0.001) significantly more than innocuous stimulation. No differences in treatment outcomes were found between adjusted and unadjusted stimulation. (a) Interferential current is very effective for chronic OA knee pain, (b) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation, (c) the fading of sensation during treatment, does not decrease the analgesic effect. Possible mechanisms explaining the findings are discussed.", "This is a double blind study that examined the optimal stimulation frequency of transcutaneous electrical nerve stimulation in reducing pain due to knee osteoarthritis.\n Thirty-four subjects were randomly allocated into 4 groups receiving transcutaneous electrical nerve stimulation at either: (i) 2 Hz; (ii) 100 Hz; (iii) an alternating frequency of 2 Hz and 100 Hz (2/100 Hz); or (iv) a placebo transcutaneous electrical nerve stimulation.\n Treatment was administered 5 days a week for 2 weeks. The outcome measures included: (i) a visual analogue scale; (ii) a timed up-and-go test; and (iii) a range of knee motion.\n The 3 active transcutaneous electrical nerve stimulation groups (2 Hz, 100 Hz, 2/100 Hz), but not the placebo group, significantly reduced osteoarthritic knee pain across treatment sessions. However, no significant between-group difference was found. Similarly, the 3 active transcutaneous electrical nerve stimulation groups, but not the placebo group, produced significant reductions in the amount of time required to perform the timed up-and-go test, and an increase in the maximum passive knee range of motion.\n Our findings suggested that 2 weeks of repeated applications of transcutaneous electrical nerve stimulation at 2 Hz, 100 Hz or 2/100 Hz produced similar treatment effects for people suffering from osteoarthritic knee." ]

[ "6352901" ]

[ "A comparison of lingualized occlusion and monoplane occlusion in complete dentures." ]

[ "Two sets of dentures, one with lingualized occlusion and the other with monoplane occlusion, were made for each of 30 edentulous patients. Sixty-seven percent of those people preferred the lingualized occlusal scheme because of improved masticatory ability, comfort, and esthetics." ]

[ "3089942", "6696302", "6680604", "7073046", "1513728", "2052637", "3970747" ]

[ "Wound infection following dog bite despite prophylactic penicillin.", "Evaluation of prophylactic oxacillin in cat bite wounds.", "Dog bites in children: epidemiology, microbiology, and penicillin prophylactic therapy.", "Prophylactic oxacillin in dog bite wounds.", "Prophylactic oral antibiotics for low-risk dog bite wounds.", "Management of early human bites of the hand: a prospective randomized study.", "The use of antibiotics in the initial management of recent dog-bite wounds." ]

[ "Dog bite wounds of 39 children (ages one to 16 years) were cultured and irrigated. Cultures showed various organisms but were of no predictive value for development of infection. By using a table of random numbers, patients were assigned to either oral penicillin V-K (100,000 U/kg/day every 6 h) or placebo for two days. All patients were seen in follow-up in three to four days and again at seven to 10 days or earlier if signs of inflammation occurred. The mean patient age, location and type of wound, and initial wound care were similar in the two treatment groups. Three of 39 (7.7%) children enrolled in the study developed infection at the bite site, including two of 19 in the penicillin group and one of 20 in the placebo group. In our study, prophylactic penicillin failed to prevent infection in dog bite wounds. Good local care on presentation seems to be the most important factor in determining future infection.", "A prospective, double-blind, placebo-controlled study was undertaken to determine the influence of prophylactic oxacillin on the frequency of infection in cat bite wounds. Adult patients with uninfected full-thickness wounds presenting within 24 hours of injury were considered. Emergency department management consisted of cleansing, irrigation, debridement, and closure as indicated; no topical antibiotics were applied. Patients were randomly assigned to receive oxacillin 500 mg qid for five days or identically appearing placebo. Home wound care was standardized and patients were observed at least every two days for a minimum of five days, or until wounds were sufficiently healed to allow discharge from the study. Clinical assessment of infection was confirmed microbiologically when possible. Twelve patients were admitted and 11 completed the study. Oxacillin (n = 5) and placebo (n = 6) groups were identical in sex, age, number of wounds per patient, wound location and type, delay to emergency department presentation, length of follow-up observation, medication compliance, and adequacy of home wound care. Four of six patients receiving placebo, but none of the five receiving oxacillin, developed a wound infection (P = .045). Material obtained from three of these four patients yielded Pasteurella multocida as the responsible organism. Prophylactic oxacillin was thus associated with a significant reduction in the frequency of infection following cat bites. We recommend such therapy in the care of these wounds.", "Fifty-five children with nonfacial dog bites were prospectively studied. Patients were assigned to an experimental group receiving oral penicillin or a control group receiving local wound care only. Wounds were cultured for anaerobic and aerobic flora prior to cleansing. Results showed that most children were bitten on an extremity by a familiar dog, sustained simple injuries, and sought prompt medical attention. The overall infection rate was 3.6%, with one patient in each group developing an infection. The most frequently recovered organisms were normal skin flora. No Pasteurella multocida were isolated. Forty percent of cultures yielded potential pathogens. Despite this finding, initial cultures of dog bite wounds had no value in predicting subsequent infection. This study suggests that routine use of prophylactic penicillin is not required for simple nonfacial dog bites in children.", "This prospective, double-blind, placebo-controlled study was undertaken to determine the value of prophylactic oxacillin in dog bites. Adult patients with uninfected full-thickness wounds presenting within 24 hours of injury were considered. Management consisted of cleansing, irrigation, debridement, and closure as indicated; no topical antibiotics were applied. Patients were randomly assigned to receive oxacillin 500 mg QID x 5 days or identically appearing placebo. Home wound care was standardized an patients were observed at least every 2 days. Clinical assessment of infection was confirmed microbiologically. Sixty-three patients were admitted and 46 completed the study. Oxacillin (22) and placebo (24) groups were identical in sex, age, number of wounds per patient, wound location and type, number of open and closed wounds, delay to presentation, length of follow-up observation, medication compliance, and adequacy of patient wound care. Two infections of the hand occurred in patients receiving oxacillin; no infections were seen among placebo-treated patients (P = NS). Prophylactic oxacillin was not associated with improved outcome. We do not advise the use of prophylactic antibiotics in dog bite injuries treated within 24 hours of accident.", "The use of prophylactic antibiotics in the initial treatment of noninfected dog bite wounds is controversial. All patients with noninfected dog bite wounds who presented to our emergency department (ED) over a two-year period were considered for entry into a randomized prospective study. Patients were excluded from the study if they had any high-risk criteria for infection: puncture wounds, hand or foot wounds, wounds greater than 12 hours old, a history of immunocompromising disorders, or the use of immunosuppressive drugs. Patients in the antibiotic group (n = 89) were treated with local wound care and given either dicloxacillin, cephalexin, or erythromycin orally for seven days. Patients in the control group (n = 96) received local wound care only. All patients had their wounds irrigated with a 1% povidone-iodine solution and debrided and sutured if clinically indicated. All patients were subsequently reevaluated for clinical signs of wound infection. The groups were similar in age, sex, time of delay in seeking treatment, anatomic sites of wounds, depths and types of wounds, and number of wounds requiring suturing. The wound infection rates for the antibiotic and control groups were 1.1 and 5.1%, respectively. This difference was not significant (P = 0.212). There were 36 wounds in the antibiotic group and 37 wounds in the control group that were full thickness. The infection rates for these wounds were 2.8 and 13.5%, respectively. This was not statistically significant (P = 0.132). This study suggests that prophylactic oral antibiotics in low-risk dog bite wounds are not indicated.", "A prospective, randomized study was undertaken to determine if mechanical care of early human bites alone is sufficient therapy in the compliant patient or if prophylactic antibiotics (oral versus parenteral) are indicated. Beginning in June of 1985, patients presenting with human bites of the hand were entered into the study if (1) the bite was less than 24 hours old, (2) the patient was free of infection, (3) the bite did not penetrate the joint capsule, and (4) there was no injury to tendon. Forty-eight patients were ultimately segregated into one of three study groups after standardized ER mechanical wound care. Fifteen patients received an oral placebo, with 7 developing infection (46.7 percent). Sixteen patients received an oral antibiotic, and 17 patients received parenteral antibiotics. No infections were found in either of these latter groups. The results statistically substantiate that mechanical wound care alone is insufficient therapy. Oral antibiotics appear to be equal to intravenous antibiotics for prophylaxis. From a cost-benefit standpoint, vigorous cleaning, debridement, and coverage with a broad-spectrum oral antibiotic are adequate care for an uncomplicated bite in the compliant patient.", "The use of antibiotics in the initial management of dog-bite wounds presented within eight hours of injury was studied. Of 211 wounds occurring in 150 patients seen during the study period, 66 wounds occurring in 33 patients comprised the study sample. All wounds were managed according to a strict protocol that included cleaning, debridement, and pressure irrigation. The wounds studied were randomly assigned to either an antibiotics (penicillinase-resistant penicillin or erythromycin) or placebo group. Two of the 35 antibiotic-treated wounds became infected, and three of the 31 placebo-treated wounds became infected. There was no significant difference in outcome between antibiotic and placebo groups. Hand wounds became infected significantly more often than other wounds. The administration of a penicillinase-resistant antibiotic is not indicated in the initial management of dog-bite wounds presented within eight hours of injury." ]

[ "12777271" ]

[ "Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic." ]

[ "The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic (long-acting injectable risperidone) in patients with schizophrenia.\n In a 12-week, multicenter, double-blind, randomized study, patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone (25 mg, 50 mg, or 75 mg). The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale.\n Of the 554 patients who were enrolled, 400 entered the double-blind study, and 370 received at least one postbaseline assessment. Mean changes in score of -6.2, -8.5, and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25-, 50-, and 75-mg risperidone groups, respectively; all three change scores were significantly different from that seen with placebo (+2.6). Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone. Long-acting risperidone was well tolerated. Adverse events related to extrapyramidal symptoms were spontaneously reported by 13% of patients receiving placebo and 10% of patients in the 25-mg risperidone group, with higher rates in the 50-mg and 75-mg groups. Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group. Mean weight changes were small in the 25-, 50-, and 75-mg risperidone groups (0.5 kg, 1.2 kg, and 1.9 kg, respectively). Injection site pain was rated as low by the patients, consistent with the investigators' pain ratings.\n Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy." ]

[ "6102739", "8549944", "4107900", "9399753", "38176", "18671816", "20393175", "4597093", "8335191", "11111780", "14563183" ]

[ "Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study.", "A controlled double blind study of azathioprine in the management of Crohn's disease.", "Controlled trial of azathioprine in Crohn's disease.", "Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial.", "National Cooperative Crohn's Disease Study: results of drug treatment.", "A multicenter, randomized, double-blind trial of everolimus versus azathioprine and placebo to maintain steroid-induced remission in patients with moderate-to-severe active Crohn's disease.", "Infliximab, azathioprine, or combination therapy for Crohn's disease.", "Treatment of Crohn's disease with azathioprine: a controlled evaluation.", "Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn's disease.", "6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease.", "Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn's disease: a randomised, investigator-blind study." ]

[ "To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohn's disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP (67%) as compared with three of 39 courses of placebo (8%) (P less than 0.001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs 6%) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36%) (P less than 0.001). The onset of response to 6-MP was often delayed, with 32% of patients taking longer than three months to respond, and 19% taking longer than four months. Adverse side effects to 6-MP occurred in 10% of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohn's disease.", "While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7% receiving placebo), p = 0.001. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p = 0.02). There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease.", "nan", "At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn's disease (CD).\n To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD.\n Patients with active CD, who have received steroids and/or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied.\n Methotrexate (12.5 mg weekly) or 6-mercaptopurine (50 mg daily), or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinically indicated.\n Eighty-four patients were included (methotrexate, 26 patients; 6-mercaptopurine, 32 patients; placebo, 26 patients). The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups. The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar. However, when each patient was evaluated as his or her own control, the reduction in steroid dose, the general well being, and the reduction in abdominal pain were significantly better in the methotrexate treated patients.\n Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD.", "The response of active and quiescent Crohn's disease to prednisone, sulfasalazine, or azathioprine has been studied in 569 patients in a placebo-controlled, randomized, multicenter cooperative trial. The response of active symptomatic disease to prednisone or sulfasalazine was significantly better than to placebo. Response to azathioprine was better than to placebo, but the difference did not reach conventional levels of statistical significance. Patients with colonic involvement were especially responsive to sulfasalazine, and those with small bowel involvement were especially responsive to prednisone. Patients' drug therapy immediately before entry to the study significantly affected subsequent response. For patients with quiescent disease, none of the drugs was superior to placebo in prophylaxis against flare-up or recurrence. There is less than a 5% risk that a clinically significant prophylactic effect of any of the drug regimens was missed.", "A prospective study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohn's disease (CD) and assess the safety and pharmacokinetics of everolimus.\n This was a randomized, double-blind, placebo-controlled, proof-of-concept study in adults with moderate-to-severe active CD. The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day, azathioprine 2.5 mg/kg/day, or placebo as maintenance treatment. The main outcome measure was the treatment success, defined as a steroid-free remission by the end of month 3 and maintained until study cutoff without the use of prohibited efficacy treatments.\n Following an interim analysis, the study was terminated before enrollment was completed due to the lack of efficacy. The full intent-to-treat population comprised 138 patients. Only 96 patients who entered the study > or =7 months prior to data cutoff were included in the primary efficacy population. The treatment success was achieved in 13 of 38 everolimus patients, 22 of 36 azathioprine patients, and 8 of 22 placebo patients. Using the Kaplan-Meier estimates at month 7, the incidence of treatment success was 22.0% with everolimus group (95% confidence interval [CI] 6.7-37.3%, P= 0.610 vs placebo), 38.3% with azathioprine group (95% CI 20.6-55.9%, P= 0.500 vs placebo), and 28.8% with placebo group (95% CI 7.7-49.9%). The type and incidence of adverse events in the everolimus cohort were similar to those reported in the approved transplantation indications.\n The safety and tolerability of everolimus (6 mg/day) in patients with active CD were comparable to azathioprine. At this dose, everolimus is not more efficacious in achieving a steroid-free remission in active CD than the comparators.", "The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.\n In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50.\n Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.\n Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)\n 2010 Massachusetts Medical Society", "nan", "The role of azathioprine (AZA) in the treatment of active Crohn's disease (CD) is still controversial. This study examined whether AZA combined with standard prednisolone therapy improved the therapeutic outcome compared with monotherapy with prednisolone.\n Forty-two patients with a Crohn's Disease Activity Index (CDAI) of > 150 were randomized into two groups. Both received 60 mg of prednisolone daily in a tapering regimen to a maintenance dose of 10 mg. In addition, group 1 received 2.5 mg AZA/kg body wt and group 2 received a placebo over the whole study period of 4 months.\n At the end of the trial, 16 of 21 patients (76%) in group 1 were in remission (CDAI < 150), compared with 8 of 21 (38%) in group 2 (P = 0.03). The CDAI in group 1 dropped from 290 +/- 97 (SD) to 72 +/- 84 and from 285 +/- 110 to 155 +/- 105 in group 2. The differences between activity indices in groups 1 and 2 became statistically significant after 8 weeks. The average prednisolone dose per day was 20.9 mg in group 1 and 26.7 mg in group 2 (P = 0.02). No major side effects were observed in this study.\n The combination of prednisolone and AZA was superior to the treatment with prednisolone alone in active CD. Patients receiving AZA showed remission more frequently, more quickly, and with lower doses of prednisolone.", "As treatment of steroid-dependent patients with inflammatory bowel disease (IBD) is controversial, we analysed the efficacy and tolerance of 6-mercaptopurine (6-MP) and methotrexate (MTX) added to prednisone in increasing and maintaining the disease remission rate.\n Seventy-two steroid-dependent IBD patients, 34 with ulcerative colitis (UC) and 38 with Crohn's disease (CD), receiving treatment with prednisone were randomly assigned in a 2:2:1 ratio to additionally receive, orally, over a period of 30 weeks 1.5 mg/kg/day of 6-MP (group A) or 15 mg/week of MTX (group B), or 3 g/day of 5-aminosalicylic acid (5-ASA) (group C). All patients who achieved remission were included in a maintaining remission study for 76 weeks. Remission was defined after stopping prednisone as a CD activity index of <150 and normal serum orosomucoid concentration for CD patients and a Mayo Clinic score <7 for UC patients.\n With regard to achieved remission, a significantly higher (P< 0.05) rate existed for UC patients in group A (78.6%) than in group C (25%), with no statistical differences in group B (58.3%) versus C. For CD patients, the rates were significantly higher (P< 0.001 and 0.01, respectively) in groups A (93.7%) and B (80%) versus C (14%). With regard to maintaining remission, UC patients in group A (63.6%) presented significantly higher rates (P < 0.0015 and P < 0.001, respectively) versus 14.3% in group B and none in group C. For CD patients, statistical differences (P < 0.001) existed when comparing rates in groups A (53.3%) and B (66.6%) versus none in group C. Noticeable side effects appeared in 13.3% of patients from group A and 11.5% from group B.\n These results suggest that 6-MP or MTX added to prednisone could be effective in steroid sparing, as well as in achieving and maintaining remission in steroid-dependent IBD patients. MTX was less effective in maintaining remission in UC patients.", "The efficacy of azathioprine in the treatment of chronic active Crohn's disease is well established. However, this drug has a long onset of action. Methotrexate has also been shown to be effective in chronic active Crohn's disease. The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine, and to establish whether methotrexate has a shorter onset of action in this setting.\n Patients with chronic active Crohn's disease were admitted to this investigator-blind study. Chronicity was defined as the need for steroid therapy of > or = 10 mg/day for at least 4 months during the preceding 12 months, with at least one attempt to discontinue treatment. The disease had to be clinically active at entry, with a Crohn's Disease Activity Index of > or = 200. Six patients treated with azathioprine and methotrexate, respectively, were found to have enterocutaneous and perianal fistulas. At entry, all patients received prednisolone (40 mg once a day) which was tapered over a period of 12 weeks unless their clinical condition deteriorated. All patients were randomised to receive i.v. methotrexate 25 mg/week, or oral azathioprine 2 mg/kg per day, for a 6-month follow-up period. After the first 3 months, methotrexate was switched to oral administration maintaining the same dose. The primary efficacy outcome considered was the proportion of patients entering first remission after 3 and 6 months of therapy. Clinical remission was defined as the lack of need for steroid treatment and a Crohn's Disease Activity Index score of < or = 150 points at each scheduled visit.\n In the 54 patients (26 F, 28 M, mean age 34 years, range 18-60) randomly assigned to methotrexate (n=27) or azathioprine (n=27), no statistically significant difference was found between the two treatment regimens with respect to remission rate after 3 (methotrexate 44%, azathioprine 33%, p=0.28, (95% CI, 0.369-0.147), and 6 months (methotrexate 56%, azathioprine 63%, p=0.39, 95% CI, 0.187-0.335), respectively. Six patients withdrew from therapy due to adverse events: 3/27 (11%) in methotrexate and 3/27 (11%) in azathioprine. Drug-related adverse events (asthenia, nausea and vomiting) that did not require withdrawal from therapy were more frequent in the methotrexate group (azathioprine: 2/27 (7%); methotrexate: 12/27 (44%), p=0.00009). The frequency of these adverse events was comparable during the intravenous or oral administration of the drug.\n This study confirms that methotrexate is effective in inducing remission in patients with chronic active Crohn's disease, therapeutic efficacy being comparable, but not faster, than that of azathioprine." ]

[ "7636093", "8430260", "8066320", "11581479", "8911385", "16137822", "11435839", "9416190", "12778828", "12576829", "1514886", "16892928", "10368193" ]

[ "Clean intermittent catheterization: safe, cost-effective bladder management for male residents of VA nursing homes.", "A comparison of open and closed catheterization techniques in rehabilitation patients.", "Bacteriuria in intermittent catheterization users: the effect of sterile versus clean reused catheters.", "Effect of a single-use sterile catheter for each void on the frequency of bacteriuria in children with neurogenic bladder on intermittent catheterization for bladder emptying.", "Clean intermittent catheterization in boys using the LoFric catheter.", "Intermittent catheterisation with hydrophilic-coated catheters (SpeediCath) reduces the risk of clinical urinary tract infection in spinal cord injured patients: a prospective randomised parallel comparative trial.", "Intermittent catheterization with a prelubricated catheter in spinal cord injured patients: a prospective randomized crossover study.", "A study comparing sterile and nonsterile urethral catheterization in patients with spinal cord injury.", "A pilot study comparing two methods of intermittent catheterization: limitations and challenges.", "A prospective randomized trial of the LoFric hydrophilic coated catheter versus conventional plastic catheter for clean intermittent catheterization.", "Clean and sterile intermittent catheterization methods in hospitalized patients with spinal cord injury.", "Intermittent catheterization in the rehabilitation setting: a comparison of clean and sterile technique.", "A comparison of prelubricated hydrophilic and non-hydrophilic polyvinyl chloride catheters for urethral catheterization." ]

[ "To compare the safety and cost of clean versus sterile intermittent bladder catheterization in male nursing home residents. To provide evidence to support the hypothesis that intermittent catheterization is a valid, alternative method of bladder management in male residents of long-term care in whom urinary retention is a documented problem.\n Randomized clinical trial.\n Three long-term care sites having predominantly male populations.\n Eighty male veterans, residents of three long-term care facilities, ranging in age from 36 to 96 years with a mean age of 72.\n Standardized procedures for clean and sterile intermittent catheterization (IC) were implemented by staff nurses at each site. Patients were randomized into clean and sterile IC groups. Nursing time and catheterization equipment usage were recorded using bar code readers. Clinical data were collected from the medical chart. Treatment of urinary tract infection was prescribed by the medical personnel responsible for each individual resident.\n We compared the number of treatment episodes for symptomatic bacteriuria between groups randomized to receive either clean or sterile intermittent catheterization. Laboratory analysis of blood and urine was done on predetermined days. Control variables were research site and patient history of urinary tract infection within the last 6 months. A cost comparison of nursing time and equipment usage for the two catheterization techniques was also performed.\n No significant differences were found between clean and sterile groups with regard to number of treatment episodes, time to first infection, type of organism cultured, or cost of antibiotic treatment. The cost of sterile technique was considerably higher both in terms of nursing time and supplies.\n Findings from this study demonstrate that clean technique intermittent catheterization is a safe and cost-effective bladder management technique with male, nursing home residents, despite the frailty of this high risk population. An annual savings of approximately $1460 per patient in nursing time and catheterization supplies could be anticipated if a patient were catheterized an average of four times per day substituting clean IC technique for sterile IC technique.", "An effective method was sought to decrease the incidence of urinary tract infections acquired by hospitalized rehabilitation patients requiring catheterization. The purpose of this study was to determine whether there was a difference in the incidence of urinary tract infections that occurred following use of two types of intermittent catheterization techniques: open catheterization and closed catheterization. The incidence of infection in both the control (open catheterization) and experimental (closed catheterization) groups was analyzed. In the control group, 9 of 14 patients (5 stroke, 4 spinal cord injured [SCI]) completed all four urine tests. Two patients developed a 20,000 colony count of enterococcus on the fourth urine sample using open catheterization. In the experimental group, 11 (4 stroke, 7 SCI) out of 16 patients maintained colony counts below 100,000 organisms per ml; one patient had a 16,000 colony count using closed catheterization. Qualitative data revealed that patients had a positive response to the closed system.", "Monthly urine cultures were analyzed at the University of Alberta Department of Medical Microbiology and Infectious Diseases to determine whether single-use sterile catheters and clean technique reduced the incidence of bacterial colonization in those using long-term intermittent self-catheterization. Thirty subjects with spina bifida, ages 3 years to 16 years, entered a crossover study with random assignment to 6 months of sterile single-use catheters or clean reused catheters. Seventeen subjects were catheterized by a parent or caregiver; 13 were responsible for self-catheterization and cleaning of the catheters. Six months of descriptive data were also collected at Alberta Children's Hospital from a similar group of subjects with spina bifida who used sterile catheters only. In the crossover group, 38% of all urine cultures were positive regardless of whether sterile single-use or clean reused catheters were employed. The other group using only sterile catheters had a 36% positive culture rate. No difference in positive cultures was found between males and females or between children who catheterized themselves and children whose parents catheterized them. The authors concluded that plastic urethral catheters may be reused.", "The frequency of bacteriuria is high in children with neurogenic bladder on intermittent catheterization for bladder emptying. In an effort to decrease bacteriuria, we examined whether the method of catheter care was responsible for the high rate of bacteriuria. For this, the frequency of bacteriuria was examined in the same patient on single-use sterile catheters and on reused clean catheters.\n A prospective, randomized, crossover trial was conducted with 10 patients who were randomized to 4 months of a new, sterile catheter for intermittent catheterization and 4 months of reuse of a clean catheter for intermittent catheterization. Each week, a urine sample was collected and symptoms of infection and medication use were recorded.\n A total of 158 urine samples were collected during 164 patient-weeks on the new catheter method for each void; 115 (73%) were positive for a pathogen. Of the 161 samples collected during 169 patient-weeks on the standard, reuse method for voiding, 123 (76%) were positive (115 [73%] of 158 vs 123 [76%] of 161). Escherichia coli was the most common pathogen detected during both method periods.\n A new, sterile catheter for each void did not decrease the high frequency of bacteriuria in patients with neurogenic bladder on intermittent catheterization.", "We compared a recently developed hydrophilic catheter to the standard polyethylene catheter in regard to hematuria, infection and patient satisfaction.\n A hydrophilic LoFric or standard Mentor catheter was assigned at random to 17 and 16 boys, respectively, who were skilled in intermittent self-catheterization. They were evaluated by weekly urinalysis and a questionnaire.\n Significantly fewer episodes of microscopic hematuria occurred in the LoFric than Mentor catheter group (9 episodes in 6 subjects versus 19 episodes in 11, p < 0.05). There were also fewer episodes of bacteriuria in the LoFric group but the difference was not statistically significant. Mean scores plus or minus standard deviation on a visual analogue scale with 0 equal to most and 10 equal to least favorable were LoFric 3.3 +/- 2.8 versus Mentor 4.9 +/- 2.7 for catheter convenience and 2.7 +/- 2.4 versus 4.2 +/- 2.6 for insertion comfort, significantly favoring the LoFric group (p < 0.05 for both). Of the 16 LoFric subjects 13 preferred to continue its use, particularly those with a history of urethral trauma or sphincteric spasm.\n In boys the LoFric catheter appears to cause less trauma. Although it is not reusable and is more expensive than the standard catheter, satisfaction is higher with the LoFric device and for select patients it has significant advantages.", "To compare the performance of SpeediCath hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters, in traumatic spinal cord injured patients presenting with functional neurogenic bladder-sphincter disorders.\n A 1-year, prospective, open, parallel, comparative, randomised, multi centre study included 123 male patients, > or =16 y and injured within the last 6 months. Primary endpoints were occurrence of symptomatic urinary tract infection (UTI) and hematuria. Secondary endpoints were development of urethral strictures and convenience of use. The main hypothesis was that coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria.\n 57 out of 123 patients completed the 12-month study. Fewer patients using the SpeediCath hydrophilic-coated catheter (64%) experienced 1 or more UTIs compared to the uncoated PVC catheter group (82%) (p = 0.02). Thus, twice as many patients in the SpeediCath group were free of UTI. There was no significant difference in the number of patients experiencing bleeding episodes (38/55 SpeediCath; 32/59 PVC) and no overall difference in the occurrence of hematuria, leukocyturia and bacteriuria.\n The results indicate that there is a beneficial effect regarding UTI when using hydrophilic-coated catheters.", "We compared the safety and patient acceptance of a conventional Nélaton and a prelubricated nonhydrophilic catheter in 18 spinal cord injured patients on intermittent catheterization.\n In a prospective crossover study each catheter was used for 7 weeks and the initial course was randomized. Urinalysis and urine culture were performed at 2, 4 and 7 weeks. Urethral trauma was evaluated by urethral cell count on the surface of each catheter used on the last day of each study period. Patient satisfaction was assessed at the end of the study by a questionnaire using multiple visual analog scales.\n Urinary tract infection was identified in 12 and 4 patients on a Nélaton and a prelubricated nonhydrophilic catheter (p = 0.03), while asymptomatic bacteruria was identified in 18 and 8 (p = 0.0244), respectively. The mean urethral cell count plus or minus standard deviation on the catheter surface was 6.7 +/- 2.8 x 10(4) and 15.1 +/- 8.9 x 10(4) for the prelubricated nonhydrophilic and the Néelaton catheter, respectively (p = 0.01). The prelubricated nonhydrophilic catheter resulted in a better mean satisfaction score than the Nélaton catheter (2.33 +/- 1.06 versus 4.72 +/- 2.13, p = 0.022). Urethral bleeding was reported in 2 patients during the study period while using the Nélaton catheter.\n The prelubricated nonhydrophilic catheter is a safe, effective and comfortable option in spinal cord injured patients on intermittent self-catheterization.", "This study was designed to determine the effect of sterile and nonsterile intermittent catheterization on the incidence of urinary tract infection (UTI) in patients after spinal cord injury. The study included 29 patients with neurogenic bladder dysfunction treated with intermittent catheterization. One group of 14 patients was on sterile catheterization; another group of 15 patients was on nonsterile catheterization. On a weekly basis, urine samples were obtained and analyzed. A total of 122 urine samples were analyzed. The patients on sterile catheterization had a 28.6% UTI incidence; the group using a nonsterile catheterization technique had a UTI incidence of 42.4%. The most common urinary pathogen in both groups was E. coli (65%). The cost of antibiotics for patients on the sterile catheterization program was only 43% of the cost of antibiotics for those on the nonsterile program. However, the sterile kits cost 371% of the cost of the catheterization kits for the patients in the nonsterile program, so the total cost of managing neurogenic bladder on the sterile program was 277% of the cost of the nonsterile program.", "Given a complex research design, a pilot study was conducted to compare a closed catheter system for intermittent catheterization to the traditional open system. Based on 33 urine samples for 11 subjects, the closed system yielded fewer positive cultures. Efforts to obtain this preliminary data proved beneficial in identifying unanticipated design limitations that will guide modifications of the main study, which will include multiple centers.", "We compared the incidence of hematuria, pyuria and clinical urinary tract infection in patients who performed intermittent self-catheterization using a hydrophilic coated LoFric (Astra Tech AB, Mölndal, Sweden) or standard plastic catheter.\n A total of 62 male patients who performed intermittent self-catheterization to manage neurogenic bladder were randomized into 2 treatment groups at 3 American study sites. Outcome measures included urinary tract infection, microhematuria, pyuria and satisfaction rates.\n Of the 62 enrolled patients 49 completed the 12-month study. The withdrawal rate was not different in the 2 groups. At the end of the study there was statistically significantly less hematuria in the hydrophilic coated catheter group compared with controls. In addition, there was a significant decrease in the urinary tract infection rate from baseline in the hydrophilic coated catheter group but not in controls.\n Use of the hydrophilic coated catheter by patients on intermittent self-catheterization is associated with less hematuria and a significant decrease in the incidence of urinary tract infections. Therefore, it may be preferable for some patients, especially those with a history of difficult catheterization, urethral trauma or a high rate of urinary tract infection.", "The purpose of this study was to compare the incidence of urinary infection using clean intermittent catheterization with the incidence of infection using sterile intermittent catheterization in patients hospitalized with spinal cord injury who were not receiving prophylactic antibiotics. Forty-six patients were assigned randomly to a clean (n = 23) or sterile (n = 23) study group. Catheterizations were done at least every six hours. Infection was defined as bacteriuria greater than or equal to 100,000 organisms/mL or greater than or equal to 10,000 organisms per mL with fever of 100 degrees F or greater. Results of urinary dipslides were recorded daily. Twenty-eight subjects (60.9%) converted to greater than or equal to 100,000 organisms per mL. Method of catheterization was neither associated significantly with development of greater than or equal to 100,000 organisms per mL. (X2[1,46] = .36, p = .55) nor with symptomatic infections (X2[1,46] = .15, p = .70). Data support the use of clean intermittent catheterization under the conditions used in this study, including the use of a sterile catheter each day and careful monitoring of infection and technique. Before using this method with other diagnostic groups or in different clinical settings, further investigation is needed.", "To compare the onset of symptomatic urinary tract infection in individuals with spinal cord injury in a rehabilitation setting who are randomized to clean or sterile intermittent catheterization technique.\n Randomized controlled design.\n Spinal cord rehabilitation units in western Canada.\n Thirty-six patients with cervical spinal cord injuries requiring intermittent catheterization by nursing staff were recruited. None had a previous history of voiding dysfunction or urinary tract infections. Interventions: Subjects were randomized to either clean or sterile intermittent catheterization technique. Protocols for both clean and sterile techniques were standardized and followed by nursing staff and caregivers.\n Primary outcome measure was symptomatic urinary tract infection as diagnosed by urine culture > or = 10(5) colony-forming units/mL, pyuria (> or =10 leukocytes on high-power field), and accompanying symptoms.\n A total of 189 urine specimens from 36 subjects were cultured. Of the 36 subjects, 15 (43%) developed a symptomatic urinary tract infection: 6/16 (37%) from the clean group; 9/20 (45%) from the sterile group (P> 0.05). Mean time to onset for symptomatic urinary tract infection for the clean group was 3.0 (standard deviation (SD) 2.4) weeks and for the sterile group, 3.6 (SD 1.3) weeks (P> 0.05). The most common urinary organisms at onset of symptomatic urinary tract infection were Enterococcus species followed by Klebsiella.\n Clean intermittent catheterization in the rehabilitation setting does not appear to place the patient with spinal cord injury at increased risk for developing symptomatic urinary tract infection, and has significant cost and time saving benefits for the health care system, as well as enhancing the transition for the patient from rehabilitation to community.", "To evaluate whether patients performing clean intermittent self-catheterization (CISC) for a short period preferred a prelubricated, hydrophilic, disposable polyvinyl chloride (PVC) catheter or a non-hydrophilic PVC catheter which could be used several times and that had to be lubricated by the patient.\n In a prospective cross-over study, 32 patients used each type of catheter for 3 weeks. After each 3-week period, the patients completed a questionnaire to assess comfort and preference, and urine specimens were obtained for culture.\n There was no significant difference between the groups in the frequency of CISC, discomfort when used, opinion on handling the catheters, preference toward one of the catheters, or of infection.\n Non-hydrophilic PVC catheters may be used safely and with no discomfort to the patient. In addition it may be possible for the healthcare system to save money, as the non-hydrophilic PVC catheters are much cheaper." ]

[ "11482465", "15274267", "17551726", "12151889", "18559469" ]

[ "Surgical treatment of resistant tennis elbow. A prospective, randomised study comparing decompression of the posterior interosseous nerve and lengthening of the tendon of the extensor carpi radialis brevis muscle.", "A comparison of open and percutaneous techniques in the surgical treatment of tennis elbow.", "Resistant tennis elbow: shock-wave therapy versus percutaneous tenotomy.", "Botulinum toxin injection versus surgical treatment for tennis elbow: a randomized pilot study.", "Radiofrequency microtenotomy: a promising method for treatment of recalcitrant lateral epicondylitis." ]

[ "We compared decompression of the posterior interosseous nerve (PIN) and lengthening of the distal tendon of the extensor carpi radialis brevis (ECRB) for treatment of tennis elbow in a randomised trial of 28 patients. Fourteen underwent decompression of PIN and 14, lengthening of ERCB. The groups did not differ significantly with regard to age, sex and work activities. The average duration of preoperative symptoms was 23 months. The PIN was exposed in the groove between the brachioradialis and brachialis muscles and decompressed at the arcade of Frohse by means of a 1-2 cm incision through the supinator muscle. The ECRB tendon was lengthened by Z-plasty at the dorsilateral aspect of the forearm. No postoperative complications occurred. The outcome after the primary operation was successful in 50% of the PIN group and in 43% of the ECRB group. Four of the 5 patients with a poor outcome were reoperated in the former group and 3 in the latter. The overall outcome after a mean follow-up of 31 months after the primary operation was successful in 60% of the cases.", "We conducted a prospective, randomised, controlled trial of 45 patients (47 elbows), with tennis elbow, who underwent either a formal open release or a percutaneous tenotomy. All patients had pre- and post-operative assessment using the Disability of Arm, Shoulder and Hand (DASH) scoring system. Both groups were followed up for a minimum of 12 months. Statistical analyses using the Mann-Whitney U test and repeated measured ANOVA showed significant improvements for patient satisfaction (p = 0.012), time to return to work (p = 0.0001), improvements in DASH score (p = 0.001) and improvement in sporting activities (p = 0.046) in the percutaneous group. Those patients undergoing a percutaneous release returned to work on average three weeks earlier and improved significantly more quickly than those undergoing an open procedure. The percutaneous procedure is a quicker and simpler procedure to undertake and produces significantly better results.", "Fifty-six patients who suffered from chronic persistent tennis elbow of more than six months duration were randomly assigned to two active treatment groups. Group 1 (n = 29) received high-energy extracorporeal shock wave treatment (ESWT; 1,500 shocks) at 18 kV (0.22 mJ/mm(2)) without local anaesthesia; group 2 (n = 27) underwent percutaneous tenotomy of the common extensor origin. Both groups achieved improvement from the base line at three weeks, six weeks, 12 weeks and 12 months post-intervention. The success rate (Roles and Maudsley score: excellent and good) at three months in the ESWT group was 65.5% and in the tenotomy group was 74.1%. ESWT appeared to be a useful noninvasive treatment method that reduced the necessity for surgical procedures.", "Surgical treatment is considered the last option for chronic tennis elbow. The purpose of this pilot study was to compare treatment with botulinum toxin infiltration of the wrist extensor, a less invasive method, with a surgical wrist extensor release (Hohmann operation). Forty patients were included in the prospective randomized study; one group of patients had surgery (n = 20), the other group of patients was treated with botulinum toxin (n = 20). The results of evaluations after 3, 6, 12, and 24 months are presented. One year after treatment 13 (65%) patients in the botulinum toxin group and 15 (75%) patients in the operative group had good to excellent results. Two years after treatment 15 patients in the botulinum toxin group (75%) had good to excellent results; four patients had been operated on after initial treatment with botulinum toxin Type A. Seventeen patients in the operative group scored good to excellent (85%) at 2 years. When analyzed with an overall scoring system, no differences were found between the two forms of treatment. Botulinum toxin infiltration, a less invasive technique, may be an alternative for surgical treatment of tennis elbow.", "Recalcitrant lateral epicondylitis (elbow tendinosis) is a common cause of elbow pain. There are many forms of treatment, none being superior.\n The main hypothesis tested in this study is that radiofrequency microtenotomy offers better results than the extensor tendon release and repair operation for elbow tendinosis, especially earlier recovery.\n Randomized controlled trial; Level of evidence, 1.\n Twenty-four patients were randomized into 2 treatment groups, extensor tendon release and repair, and microtenotomy. Dynamic infrared thermography (DIRT) was employed as an objective method to verify the diagnosis as well as to document the outcome 3 months after the surgical procedure.\n Visual analog scale pain scores in the microtenotomy but not in the release group decreased significantly after 3 weeks. There was no statistically significant difference in pain scores between the 2 groups at 3, 6, and 12 weeks, and at 10 to 18 months. At 12 weeks, grip strength had improved significantly in the microtenotomy but not in the release group. The functional score was significantly increased in both groups. The DIRT group showed significant differences in epicondyle skin temperature between diseased and normal elbows both pre- and postoperatively. Abnormal DIRT images correlated well with elevated pain scores.\n Radiofrequency microtenotomy provides a promising alternative to the release operation for elbow tendinosis. Dynamic infrared thermography provides a reliable, noninvasive, objective method for the diagnosis of elbow tendinosis, as well as for evaluation of the outcome following treatment." ]

[ "12426500", "11763866" ]

[ "Three-year clinical comparison of survival of endodontically treated teeth restored with either full cast coverage or with direct composite restoration.", "Clinical evaluation of fiber-reinforced epoxy resin posts and cast post and cores." ]

[ "Little information exists regarding the outcome of crown build-ups on endodontically treated teeth restored with metal-ceramic crowns or with only a direct-placed composite.\n The aim of this study was to evaluate the clinical success rate of endodontically treated premolars restored with fiber posts and direct composite restorations and compare that treatment with a similar treatment of full-coverage with metal-ceramic crowns.\n Subjects included in this study had one maxillary or mandibular premolar for which endodontic treatment and crown build up was indicated and met specific inclusion/exclusion criteria. Only premolars with Class II carious lesions and preserved cusp structure were included. Subjects were randomly assigned to 1 of the following 2 experimental groups: (1) teeth endodontically treated and restored with adhesive techniques and composite or (2) teeth endodontically treated, restored with adhesive techniques and composite, and then restored with full-coverage metal-ceramic crowns. Sixty teeth were included in the first group and 57 in the second. All restorations were performed by one operator. Causes of failure were categorized as root fracture, post fracture, post decementation, clinical and/or radiographic evidence of marginal gap between tooth and restoration, and clinical and/or radiographic evidence of secondary caries contiguous with restoration margins. Subjects were examined for the listed clinical and radiographic causes of failure by 2 calibrated examiners at intervals of 1, 2, and 3 years. Exact 95% confidence intervals for the difference between the 2 experimental groups were calculated.\n At the 1-year recall, no failures were reported. The only failure modes observed at 2 and 3 years were decementations of posts and clinical and/or radiographic evidence of marginal gap between tooth and restoration. There was no difference in the failure frequencies of the 2 groups (95% confidence interval, -17.5 to 12.6). There was no difference between the number of failures caused by post decementations and the presence of marginal gaps observed in the 2 groups (95% confidence intervals, -9.7 to 16.2 and -17.8 to 9.27).\n Within the limitations of this study, the results upheld the research hypothesis that the clinical success rates of endodontically treated premolars restored with fiber posts and direct composite restorations after 3 years of service were equivalent to a similar treatment of full coverage with metal-ceramic crowns.", "This retrospective study evaluated treatment outcome of cast post and core and Composipost systems after 4 yrs of clinical service.\n 200 patients were included in the study. They were divided in two groups of 100 endodontically treated teeth restored with a post. Group 1: Composipost systems were luted into root canal following the manufacturer's instructions. Group 2: Cast post and cores were cemented into root canal preparations with a traditional technique. The patients were recalled after 6 months, 1, 2 and 4 yrs and clinical and radiographic examinations were completed. Endodontic and prosthodontic results were recorded.\n Group 1: 95% of the teeth restored with Composiposts showed clinical success; 3% of these samples were excluded for noncompliance and 2% showed endodontic failure. Group 2: Clinical success was found with 84% of teeth restored with cast post and core. 2% of these samples were excluded for noncompliance, 9% showed root fracture, 2% dislodgment of crown and 3% endodontic failure. Statistical evaluation showed significant differences between Groups 1 and 2 (P < 0.001). The results of this retrospective study indicated that the Composipost system was superior to the conventional cast post and core system after 4 yrs of clinical service." ]

[ "11790211", "12574925", "11412248", "12085142", "12103285", "15141043", "12399854", "9117320", "10749610", "11865378", "15081650", "11116420", "12972969", "11805557", "9660024", "11851660", "15048739", "12195192", "12454514", "9678378", "12145073" ]

[ "Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial.", "Randomized controlled trial of laparoscopic versus open colectomy for advanced colorectal cancer.", "Randomized clinical trial of the effect of open versus laparoscopically assisted colectomy on systemic immunity in patients with colorectal cancer.", "Wound complications of laparoscopic vs open colectomy.", "Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial.", "A comparison of laparoscopically assisted and open colectomy for colon cancer.", "Comparison of surgical stress between laparoscopic and open colonic resections.", "Prospective randomized study of laparoscopic versus open colonic resection for adenocarcinoma.", "Systemic cytokine response after laparoscopic-assisted resection of rectosigmoid carcinoma: A prospective randomized trial.", "Prospective evaluation of laparoscopy-assisted colectomy versus laparotomy with resection for management of complex polyps of the sigmoid colon.", "Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial.", "Laparoscopically assisted colon resection for colon carcinoma: perioperative results and long-term outcome.", "Interleukin-6, C-reactive protein, and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells in patients after laparoscopic vs. conventional bowel resection: a randomized study.", "Prospective, randomized trial comparing laparoscopic vs. conventional surgery for refractory ileocolic Crohn's disease.", "A prospective, randomized trial comparing laparoscopic versus conventional techniques in colorectal cancer surgery: a preliminary report.", "Randomized clinical trial of laparoscopic versus open abdominal rectopexy for rectal prolapse.", "Randomized clinical trial of the costs of open and laparoscopic surgery for colonic cancer.", "Metabolic and functional results after laparoscopic colorectal surgery: a randomized, controlled trial.", "Laparoscopic versus open colorectal surgery: a randomized trial on short-term outcome.", "Laparoscopic-assisted vs. open surgery for colorectal cancer: comparative study of immune effects.", "Temperature control and recovery of bowel function after laparoscopic or laparotomic colorectal surgery in patients receiving combined epidural/general anesthesia and postoperative epidural analgesia." ]

[ "Laparoscopic-assisted colectomy (LAC) has emerged as the preferred minimally invasive surgical strategy for diseases of the colon. The safety and efficacy of LAC for colon cancer are unknown, and the nature and magnitude of any quality-of-life (QOL) benefit resulting from LAC for colon cancer is also unknown.\n To compare short-term QOL outcomes after LAC vs open colectomy for colon cancer.\n Multicenter, randomized controlled trial (Clinical Outcomes of Surgical Therapy [COST]). Between September 1994 and February 1999, 37 of 48 centers provided data for the QOL component of the trial for 449 consecutive patients with clinically resectable colon cancer.\n Scores on the Symptoms Distress Scale (SDS), Quality of Life Index, and a single-item global rating scale at 2 days, 2 weeks, and 2 months postoperative; duration of postoperative in-hospital analgesic use; and length of stay.\n Of 449 patients, 428 provided QOL data. In an intention-to-treat analysis comparing SDS pain intensity, SDS summary, QOL Index summary, and global rating scale scores at each time point, the only statistically significant difference observed between groups was the global rating scale score for 2 weeks postsurgery. The mean (median) global rating scale scores for 2 weeks postsurgery were 76.9 (80) for LAC vs 74.4 (75) for open colectomy (P =.009). While in the hospital, patients assigned to LAC required fewer days of both parenteral analgesics compared with patients assigned to open colectomy (mean [median], 3.2 [3] vs 4.0 [4] days; P<.001) and oral analgesics (mean [median], 1.9 [1] vs 2.2 [2] days; P =.03).\n Only minimal short-term QOL benefits were found with LAC for colon cancer compared with standard open colectomy. Until ongoing trials establish that LAC is as effective as open colectomy in preventing recurrence and death from colon cancer, this procedure should not be offered to patients with colon cancer.", "After confirming a favorable outcome of laparoscopic surgery for early colorectal cancer, we conducted a randomized controlled trial to compare short-term outcomes of laparoscopic and open colectomy for advanced colorectal cancer.\n Fifty-nine patients with T2 or T3 colorectal cancer were randomized to undergo laparoscopic (n = 29) or open (n = 30) colectomy. Median follow-up was 20 months (range, 6-34 months).\n Operative time was longer (p <0.0001) and blood loss (p = 0.0034) and postoperative analgesic requirement were less in the laparoscopic group than in the open group. An earlier return of bowel motility and earlier discharge from the hospital (p = 0.0164) were observed after laparoscopic surgery. Serum C-reactive protein levels on postoperative days 1 (p <0.0001) and 4 (p = 0.0039) were lower in the laparoscopic group than in the open group. Postoperative complications did not differ between the two groups.\n Laparoscopic surgery for advanced colorectal cancer is feasible, with favorable short-term outcome.", "Laparoscopic surgery is believed to produce an attenuated metabolic stress response and to have a less dampening effect on the immune response than open surgery. To date, the effect has not been studied in a randomized clinical trial of colorectal cancer.\n The study was a two-armed randomized prospective trial conducted in parallel with the UK Medical Research Council's Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (CLASICC) trial comparing laparoscopically assisted colorectal surgery for left-sided tumours with conventional open surgery. Systemic immunity was assessed by determining the T- and B-cell counts, the CD4 : CD8 ratio, the natural killer cell counts, the immunoglobulin (Ig) G, IgM and IgA levels, and C3 and C4 levels. The white cell phagocytic activity (nitroblue tetrazolium test) was studied before operation and on the third postoperative day.\n A total of 236 patients were randomized in the immune study between 11 March 1997 and 14 August 1999; 161 had complete preoperative and postoperative assays for the analysis of results. There was no difference in mean response between the two surgical groups for each of the immune parameters studied. The unadjusted difference for the primary endpoint, T-cell count, 3 days after operation was - 1.6 per cent (95 per cent confidence interval - 5.0 to 1.8 per cent).\n There is no difference in the systemic immune response in patients having laparoscopically assisted colectomy compared with those undergoing conventional open surgery for colorectal cancer.", "This study was conducted to determine if laparoscopic colon surgery has changed the incidence of wound complications after colon resection.\n Eighty-three patients were randomized to undergo either laparoscopic (LCR) or open colon resection (OCR) for cancer at our institution as part of a multicenter trial. Data were tabulated from review of the prospective database and physician records.\n Thirty-seven patients were randomized to LCR and 46 to OCR. Seven patients in the LCR group were converted to OCR. LCR was performed using a limited midline incision for anastomosis and specimen extraction. Incision length was significantly greater (p <0.001) in the OCR group (19.4 +/- 5.6 cm) compared to the LCR extraction site (6.3 +/- 1.4 cm). Wound infections occurred in 13.5% of patients after LCR (2.7% trocar, 10.8% extraction sites) and in 10.9% of patients after OCR. Over a mean follow-up period of 30.1 +/- 17.8 months, incisional hernias developed in 24.3% of patients after LCR and 17.4% after OCR. In the LCR group, extraction sites accounted for 85.7% of all wound complications.\n The extraction site for LCR is associated with a high incidence of complications, comparable to open colectomy. Strategies to alter operative technique should be considered to reduce the incidence of these complications.", "Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival.\n From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle.\n 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively).\n LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.", "Minimally invasive, laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer. Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence (based on frequent reports of tumor recurrences within surgical wounds) prompted a controlled trial evaluation.\n We conducted a noninferiority trial at 48 institutions and randomly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons. The median follow-up was 4.4 years. The primary end point was the time to tumor recurrence.\n At three years, the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group (two-sided P=0.32; hazard ratio for recurrence, 0.86; 95 percent confidence interval, 0.63 to 1.17). Recurrence rates in surgical wounds were less than 1 percent in both groups (P=0.50). The overall survival rate at three years was also very similar in the two groups (86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group; P=0.51; hazard ratio for death in the laparoscopic-surgery group, 0.91; 95 percent confidence interval, 0.68 to 1.21), with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer. Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group, as reflected by a shorter median hospital stay (five days vs. six days, P<0.001) and briefer use of parenteral narcotics (three days vs. four days, P<0.001) and oral analgesics (one day vs. two days, P=0.02). The rates of intraoperative complications, 30-day postoperative mortality, complications at discharge and 60 days, hospital readmission, and reoperation were very similar between groups.\n In this multi-institutional study, the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy, suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer.\n Copyright 2004 Massachusetts Medical Society", "The magnitude of surgical trauma after laparoscopic and open colonic resection was evaluated by examining postoperative serum values of interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and granulocyte elastase (GE) for further evidence of the benefit realized with minimally invasive approaches in colonic surgery.\n Altogether, 42 patients with Crohn's disease (n = 20) or colon carcinomas/adenomas (n = 22) were matched by age, gender, body mass index (BMI), and Crohn's Disease Activity Index for either a laparoscopic (n = 21) or an open colonic resection (n = 21). In both groups the postoperative serum levels of IL-6, IL-10, C-RP, and granulocyte elastase were determined, as indicators of surgical stress.\n Laparoscopic and open colonic resection caused a significant increase in serum IL-6, IL-10, CRP, and granulocyte elastase levels. The comparison between laparoscopic and open colonic resections, however, showed significantly lower serum IL-6, IL-10, CRP, and granulocyte elastase levels after laparoscopic colonic resection, which was most evident for IL-6 and granulocyte elastase.\n Our study demonstrated that IL-6 and granulocyte elastase may be appropriated particularly to monitor surgical stress. By using these parameters, we found a significant reduction in surgical trauma after laparoscopic surgery, was compared with the open procedure. This supports the clinical findings of a clear benefit for patients undergoing laparoscopic colonic surgery.", "Laparoscopic techniques have been evaluated for many operations, but retrospective and prospective studies have failed to show these techniques to be superior to open operations in all patients with colorectal disease. This study compares laparoscopic and open colonic resection in a randomized fashion with special reference to outcome, complications and immunomodulation.\n The clinical course, assessment of convalescence parameters, immunofunction and pathological evaluation of the operative specimen were compared in 34 patients with colonic adenocarcinoma. The patients were randomized to either laparoscopic surgery (group 1, n = 18) or open surgery (group 2, n = 16). As five patients were excluded the number of patients was 15 in group 1 and 14 in group 2.\n Patients in group 1 were discharged earlier (P < 0.05) and suffered less pain (P < 0.01 at rest, P < 0.05 during coughing and mobilization). Surgery was equally radical in the two groups. Intraoperative bleeding, postoperative reduction in pulmonary function, and level of fatigue were identical in the two groups. The immunodepression was more pronounced in patients in group 1 (P < 0.01).\n Laparoscopic colonic resection is an acceptable and safe alternative to open procedures; the differences between the two techniques are not marked.", "To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma.\n Laparoscopic resection of colorectal carcinoma is technically feasible, but objective evidence of its benefit is scarce. Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response.\n Thirty-four patients with rectosigmoid carcinoma, without evidence of metastatic disease and suitable for laparoscopic resection, were randomized to undergo either laparoscopic (n = 17) or conventional open (n = 17) resection of the tumor. Clinical parameters were recorded. Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein. The primary end points were the cytokine and C-reactive protein levels. Data were analyzed by intention to treat.\n The demographic data of the two groups were comparable. The clinical outcome of both groups was satisfactory, with no surgical deaths and a reasonable complication rate. Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery, with the responses in the laparoscopic group significantly less than those in the open group. C-reactive protein levels peaked at 48 hours, and the difference was also statistically significant. Levels of tumor necrosis factor-alpha were not elevated after surgery, and there was no difference between the groups.\n Tissue trauma, as reflected by systemic cytokine response, was less after laparoscopic resection than after open resection of rectosigmoid carcinoma. The difference in the systemic cytokine response may have implications on the long-term survival.", "Laparoscopy-assisted colectomy is technically feasible, but objective evidence of its benefits remains scarce. This study was done to evaluate the outcomes and operative stress of laparoscopy-assisted colectomy versus the traditional open method in the management of sigmoid complex polyps that cannot be safely or adequately removed by colonofibroscopy. Between January 1997 and December 1999, a total of 42 patients were equally randomized to the laparoscopy group and the laparotomy group by the blocked randomization method. Three patients randomized to the laparoscopy group did not complete the trial; therefore 18 patients treated by laparoscopy-assisted sigmoidectomy and the other 21 treated by the open method were prospectively evaluated. These two groups of patients were well matched in age, gender, symptoms, tumor location, localization method, tumor size, morphology, histopathology, and the accuracy of the clinical diagnosis. Two standardized surgical strategies, the lateral-to-medial and medial-to-lateral dissection sequences, were performed in 14 and 4 patients of the laparoscopy group, respectively, according to whether their tumors were located above or below 20 cm above the anal verge. After evaluating the surgical outcomes, we found that the laparoscopy group was significantly better than the laparotomy group in regard to parameters that included severity of postoperative pain, wound size, postoperative complication rate, and the duration of postoperative ileus, hospitalization, and disability. There was no significant difference in the operating times for these two groups. However, the costs of the laparoscopy group were significantly higher. To evaluate the surgical stress, we measured the serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), total lymphocyte count, and CD4+/CD8+ ratio 24 hours before and after surgery. We found that the postoperative serum CRP level and the ESR were significantly less elevated and the total lymphocyte counts and CD4+/CD8+ ratio were significantly less depressed in the laparoscopy group than in the laparotomy group. We thus concluded that laparoscopy-assisted sigmoidectomy can be safely performed with shorter convalescence and less operative stress but at a higher cost. We strongly recommended the use of this technique in the management of sigmoid complex polyps if the patient's economic status permits.", "Although laparoscopic resection of colorectal carcinoma improves post-operative recovery, long-term survival and disease control are the determining factors for its application. We aimed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer.\n From Sept 21, 1993, to Oct 21, 2002, 403 patients with rectosigmoid carcinoma were randomised to receive either laparoscopic assisted (n=203) or conventional open (n=200) resection of the tumour. Survival and disease-free interval were the main endpoints. Patients were last followed-up in March, 2003. Perioperative data were recorded and direct cost of operation estimated. Data were analysed by intention to treat.\n The demographic data of the two groups were similar. After curative resection, the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1% (SE 3.7%) and 72.9% (4.0%) respectively. The probabilities of being disease free at 5 years were 75.3% (3.7%) and 78.3% (3.7%), respectively. The operative time of the laparoscopic group was significantly longer, whereas postoperative recovery was significantly better than for the open resection group, but these benefits were at the expense of higher direct cost. The distal margin, the number of lymph nodes found in the resected specimen, overall morbidity and operative mortality did not differ between groups.\n Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients. The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes.", "The role of laparoscopic colon resection in the management of colon cancer is unclear. The aims of this study were to compare perioperative results and long-term outcomes in patients randomized to either open (O) or laparoscopically assisted (LA) colon resection for colon cancer.\n A prospective randomized trial comparing O to LA colon resection was conducted from January 1993 to November 1995. Preoperative workup, intraoperative results, complications, length of stay, pathologic findings, and long-term outcomes were compared between the two groups. Statistical analysis was performed with t-test. Follow-up periods ranged from 3.5 to 6.3 years (mean, 4.9 years).\n No port-site or abdominal wall recurrences were noted in any patients. [table: see text]\n These results suggest that laparoscopically assisted colon resection for malignant disease can be performed safely, with morbidity, mortality, and en bloc resections comparable with those of open laparotomy. Long-term (5-year) follow-up assessment shows similar outcomes in both groups of patients, demonstrating definite perioperative advantages with LA surgery and no perioperative or long-term disadvantages.", "The aim of the study was to investigate the effect of surgical trauma in terms of approach (laparoscopic vs. conventional surgery) and extent of bowel resection (ileocolic resection vs. colectomy) on interleukin-6 level, C-reactive protein level, and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells. Second, the length of the incision was correlated with the inflammatory response.\n Thirty-four patients were analyzed as part of a randomized trial comparing laparoscopically assisted vs. open bowel resection for Crohn's disease, ulcerative colitis, and familial adenomatous polyposis. C-reactive protein levels and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells were measured preoperatively and one day after surgery. Interleukin-6 was measured preoperatively and on Days 1 and 7 postoperatively.\n Four of the 34 patients were excluded because of blood transfusion after surgery. One day postoperatively, the interleukin-6 level peaked significantly within the laparoscopic and conventional group. There was no significant difference between the conventional and laparoscopic groups at Day 1 postoperatively. At Day 7 postoperatively, interleukin-6 levels were similar in both groups and returned to baseline levels. There was a higher C-reactive protein level in the conventional group one day after surgery than in the laparoscopic group, although the difference was not significant. Preoperative and postoperative human leukocyte antigen-DR expression on monocytes and postoperative percentage of lymphocytes expressing human leukocyte antigen-DR did not differ between the conventional and laparoscopic groups. No differences in immune response with respect to the measured parameters were noticed in patients with a large or small bowel resection segment or in patients with a small (</=8 cm) or large (>8 cm) incision.\n These data suggest that surgical trauma did not significantly affect the immune status of patients with respect to the measured parameters in terms of either the approach or the extent of bowel resection.", "Surgeons have been reluctant to apply laparoscopic techniques to Crohn's disease surgery because of concerns with evaluating and excising inflamed tissue using laparoscopic methods. Additionally in Crohn's disease surgery, laparoscopic techniques have not been demonstrated to have clear advantages over conventional ones.\n We conducted a prospective, randomized trial in one surgical department comparing laparoscopic vs. conventional techniques in 60 patients (25 males), median age 34.4 (range, 10-60.1) years, undergoing elective ileocolic resection for refractory Crohn's disease. Postoperatively, all patients underwent measurement of pulmonary function tests every 12 hours, and were treated identically on a highly controlled protocol with regard to analgesic administration, feeding, and postoperative care.\n Of the 31 patients assigned to laparoscopic and 29 to the conventional group, all had isolated Crohn's disease of the terminal ileum plus or minus the cecum. Median length of the incision was 5 cm in the laparoscopic group and 12 cm in the conventional group. Overall recovery of 80 percent of forced expiratory volume (one second) and forced vital capacity was a median of 2.5 days for laparoscopic and 3.5 days for conventional (P = 0.03). There was no difference in the amount of morphine equivalents used between groups postoperatively. Flatus and first bowel movement returned a median of 3 and 4 days, respectively, after laparoscopic vs. 3.3 and 4 days, respectively, after conventional surgery (P = 0.21). Median length of stay was five (range, 4-30) days for laparoscopic, and six (range, 4-18) days for conventional surgery. Major complications occurred in one patient in each group. Minor complications occurred in four laparoscopic and eight conventional patients (P < 0.05). There were no deaths. Two laparoscopic patients were converted to conventional as a result of adhesions or inflammation. All patients recovered well and there were no clinical recurrences in the follow-up period (median, 20; range, 12-45 months).\n Within a single institution, single surgical team, prospective, randomized trial, laparoscopic techniques offered a faster recovery of pulmonary function, fewer complications, and shorter length of stay compared with conventional surgery for selected patients undergoing ileocolic resection for Crohn's disease.", "Uncontrolled studies using laparoscopic techniques in colorectal surgery have not demonstrated clear advantages to these procedures compared with conventional ones, and surgeons are concerned about unusual early recurrences reported after laparoscopic colorectal cancer surgery.\n We conducted a prospective, randomized trial in one surgical department comparing laparoscopic (LAP) and conventional (CON) techniques in 109 patients undergoing bowel resection for colorectal cancers or polyps. Postoperatively, all patients underwent measurement of pulmonary function tests every 12 hours, and were treated identically on a highly controlled protocol with regard to analgesic administration, feeding, and postoperative care.\n Of the 55 patients assigned to LAP and 54 to the CON group, there were 42 and 38 with cancer, respectively (the other patients had large adenomas). Overall recovery of 80% of forced expiratory volume in 1 second and forced vital capacity was a median of 3 days for LAP and 6.0 days for CON (p = 0.01). LAP patients used significantly less morphine than CON patients up to the second day after surgery (0.78 +/- 0.32 versus 0.92 +/- 0.34 mg/kg per day, p = 0.02). Flatus returned a median of 3.0 days after LAP versus 4.0 days after CON surgery (p = 0.006). Tumor margins were clear in all patients. After a median followup of 1.5 years (LAP) and 1.7 years (CON), there were no port site recurrences in the LAP group. Seven cancer-related deaths have occurred (three in the LAP group, four in the CON group).\n Within this prospective, randomized trial, laparoscopic techniques were as safe as conventional surgical techniques and offered a faster recovery of pulmonary and gastrointestinal function compared with conventional surgery for selected patients undergoing large bowel resection for cancer or polyps. There were no apparent shortterm oncologic disadvantages. Longer followup is needed to fully assess oncologic outcomes.", "The objectives of this study were to compare both subjective clinical outcomes and the objective stress response of laparoscopic and open abdominal rectopexy in patients with full-thickness rectal prolapse. Abdominal rectopexy for patients with rectal prolapse is well suited for a laparoscopic approach as no resection or anastomosis is necessary.\n Forty patients with a full-thickness rectal prolapse were randomized before operation to a laparoscopic group and an open group. They agreed to conform to a clinical pathway (CP) of liquid diet (CP1) and full mobility (CP2) on day 1, solid diet (CP3) on day 2 and discharge (CP4) before day 5. Their compliance was monitored by an assessor blinded to the operative group, who also rated pain and mobility. Patient-controlled morphine use was documented. Neuroendocrine and immune stress response and respiratory function were measured.\n Some 75 per cent of all clinical pathway objectives of early recovery were achieved in the laparoscopic group compared with 37 per cent in the open group (P < 0.01). Significant differences in favour of laparoscopy were noted with regard to narcotic requirements, and pain and mobility scores. Differences in objective measures of stress response favouring laparoscopy were found for urinary catecholamines, interleukin 6, serum cortisol and C-reactive protein. No differences were noted in respiratory function but significant respiratory morbidity was greater in the open group (P < 0.05). None of the measured outcomes, subjective or objective, favoured the open group apart from operating time, which was significantly shorter (153 versus 102 min; P < 0.01).\n This study has demonstrated significant subjective and objective differences in favour of a laparoscopic technique for abdominal rectopexy. The advantages were all short term but no evidence of any adverse effect on longer-term outcomes was observed.", "There has been no randomized clinical trial of the costs of laparoscopic colonic resection (LCR) compared with those of open colonic resection (OCR) in the treatment of colonic cancer.\n A subset of Swedish patients included in the Colon Cancer Open Or Laparoscopic Resection (COLOR) trial was included in a prospective cost analysis; costs were calculated up to 12 weeks after surgery. All relevant costs to society were included. No effects of the procedures, such as quality of life or survival, were taken into account.\n Two hundred and ten patients were included in the primary analysis, 98 of whom had LCR and 112 OCR. Total costs to society did not differ significantly between groups (difference in means for LCR versus OCR euro1846; P = 0.104). The cost of operation was significantly higher for LCR than for OCR (difference in means euro1171; P < 0.001), as was the cost of the first admission (difference in means euro1556; P = 0.015) and the total cost to the healthcare system (difference in means euro2244; P = 0.018).\n Within 12 weeks of surgery for colonic cancer, there was no difference in total costs to society incurred by LCR and OCR. The LCR procedure, however, was more costly to the healthcare system.\n Copyright 2004 British Journal of Surgery Society Ltd.", "This study was designed to compare metabolic and functional results after laparoscopic and open colorectal resection.\n Seventy-nine patients were randomly assigned to laparoscopic (n = 40) or open (n = 39) colorectal resection. Before and after operation, the following parameters were determined: respiratory function (spirography and blood gas); serum level of cortisol, lactate, and C-reactive protein; total lymphocyte count; and CD4 and CD8 lymphocyte subsets. Intraoperative core temperature was measured by a bladder probe. Postoperative pain and analgesic consumption were also monitored.\n Mild operative hypothermia, a trend to postoperative reduction of total lymphocyte count, and significant impairment of respiratory function early after surgery were found in both groups. Laparoscopy showed a higher CD4/CD8 ratio (P = 0.01) on postoperative Day 1 and a faster return of C-reactive protein to preoperative values (P = 0.01) than in the open colorectal resection group. Morphine consumption in the first 48 hours after surgery was lower in the laparoscopic than in the open group (P = 0.02).\n Laparoscopy was associated with a less pronounced immunosuppression and inflammatory response and a lower consumption of analgesic drugs than open surgery. Moreover, our data did not show any additional detrimental effect of laparoscopy on either operative core temperature or early postoperative respiratory function.", "The primary endpoint was to compare the impact of laparoscopic and open colorectal surgery on 30-day postoperative morbidity. Lymphocyte proliferation to mitogens and gut oxygen tension were surrogate endpoints.\n Evidence-based proof of the effect of laparoscopic colorectal surgery on immunometabolic response and clinically relevant outcome variables is scanty. Further randomized trials are desirable before proposing laparoscopy as a superior technique.\n Two hundred sixty-nine patients with colorectal disease were randomly assigned to laparoscopic (n = 136) or open (n = 133) colorectal resection. Four trained members of the surgical staff who were not involved in the study registered postoperative complications. Lymphocyte proliferation to Candida albicans and phytohemagglutinin was evaluated before and 3 and 15 days after surgery. Operative gut oxygen tension was monitored continuously by a polarographic microprobe.\n In the laparoscopic group the conversion rate was 5.1%. The overall morbidity rate was 20.6% in the laparoscopic group and 38.3% in the open group. Postoperative infections occurred in 15 of the 136 patients in the laparoscopic group and 31 of the 133 patients in the open group. The mean length of hospital stay was 10.4 +/- 2.9 days in the laparoscopic group and 12.5 +/- 4.1 days in the open group. On postoperative day 3, lymphocyte proliferation was impaired in both groups. Fifteen days after surgery, the proliferation index returned to baseline values only in the laparoscopic group. Intraoperative gut oxygen tension was higher in the laparoscopic than in the open group.\n Laparoscopic colorectal surgery resulted in a significant reduction of 30-day postoperative morbidity. Lymphocyte proliferation and gut oxygen tension were better preserved in the laparoscopic group than in the open group.", "Our aim was to test the hypothesis that laparoscopic-assisted resection for colorectal cancer has an immunologic advantage over traditional open surgery.\n Sixteen patients with colorectal cancer were randomized to undergo laparoscopic-assisted resection or open surgery. Basic patient data were recorded, and serum interleukin-6 levels, relative proportions of lymphocytes, and human leukocyte antigen-DR expression on monocytes were determined at specific time intervals.\n Operating time was longer for laparoscopic-assisted resection (P=0.02), but analgesic requirements were less (P=0.04). All patients exhibited the following: interleukin-6 levels increased to a maximum at 4 hours and returned to preoperative levels within 48 hours. This response appeared greater for open resection (mean peak level, 313 vs. 173 pg/ml; P=0.25). Relative granulocytosis (P < 0.001) was seen within 48 hours, which was offset by a decrease in percentage of lymphocytes (P < 0.001). Changes in lymphocyte subfractions were most significant seven days postsurgery: natural killer cells decreased (P=0.003); T cells increased (P=0.008), with elevation in the CD4/CD8 ratio (P=0.003). B cells were largely unchanged at all time periods. Human leukocyte antigen-DR expression on monocytes was significantly less at 48 hours postsurgery (P < 0.001). All changes were reversed within three weeks of surgery. There were no differences when comparing laparoscopic-assisted resection with open surgery.\n Both laparoscopic-assisted resection and open surgery affect the immune response. It would appear that laparoscopic-assisted resection does not have an immunologic advantage over open surgery in patients with colorectal cancer.", "We compared the effects of a laparoscopic (n = 23) versus laparotomic (n = 21) technique for major abdominal surgery on temperature control in 44 patients undergoing colorectal surgery during a combined epidural/general anesthesia. A thoracic epidural block up to T4 was induced with 6-10 mL of 0.75% ropivacaine; general anesthesia was induced with thiopental, fentanyl, and atracurium IV and maintained with isoflurane. Core temperature was measured with a bladder probe and recorded every 15 min after the induction. In both groups, core temperature decreased to 35.2 degrees C (range, 34 degrees C-36 degrees C) at the end of surgery. After surgery, normothermia returned after 75 min (60-120 min) in the Laparoscopy group and 60 min (45-180 min) in the Laparotomy group (P = 0.56). No differences in postanesthesia care unit discharge time were reported between the two groups. The degree of pain during coughing was smaller after laparoscopy than laparotomy from the 24th to the 72nd observation times (P < 0.01). Morphine consumption was 22 mg (2-65 mg) in the Laparotomy group and 5 mg (0-45 mg) in the Laparoscopy group (P = 0.02). The time to first flatus was shorter after laparoscopy (24 h [16-72 h]) than laparotomy (72 h [26-96 h]) (P = 0.0005), and the first intake of clear liquid occurred after 48 h (24-72 h) in the Laparoscopy group and after 96 h (90-96 h) in the Laparotomy group (P = 0.0005). Although laparoscopic surgery provides positive effects on the degree of postoperative pain and recovery of bowel function, the reduction in heat loss produced by minimizing bowel exposure with laparoscopic surgery does not compensate for the anesthesia-related effects on temperature control, and active patient warming must also be used with laparoscopic techniques.\n This prospective, randomized, controlled study demonstrates that laparoscopic colorectal surgery results in less postoperative pain and earlier recovery of bowel function than conventional laparotomy but does not reduce the risk for perioperative hypothermia. Accordingly, active warming must be provided to patients also during laparoscopic procedures." ]

[ "830880", "10093144" ]

[ "Hydrocortisone therapy in meconium aspiration syndrome: a controlled study.", "The role of pulmonary inflammation in the development of pulmonary hypertension in newborn with meconium aspiration syndrome (MAS)." ]

[ "To evaluate the efficacy of glucocorticoids in the treatment of infants with meconium aspiration syndrome, a double-blind study using hydrocortisone or a lactose placebo was undertaken. Thirty-five infants were included in the study. No significant differences in arterial Po2, Pco2, pH, A-aDo2 gradients, in requirement for assisted ventilation, or in survival were domonstrated between the groups. In control infants, a significant decrease (p less than 0.01) in respiratory distress score was found at 48 to 72 hours of age; in treated infants, it was seen only after 72 hours. The infants in the treated group took a significantly longer (p less than 0.01) period of time to wean to room air than those in the control group (68.9 +/- 9.6 hours vs 36.6 +/- 6.9 hours). On the basis of these observations, hydrocortisone is not recommended for treatment of MAS.", "1. There was no clear correlation between the tracheal aspirate cytokines and the elevation of pulmonary arterial pressure in newborn piglets with MAS. The use of dexamethasone significantly suppressed tracheal aspirate cytokines but did not significantly alter pulmonary arterial pressure. Dexamethasone significantly increased the cardiac stroke volume and blood pressure. 2. Early dexamethasone therapy (< 12 hrs) for one week in infants with MAS significantly improved pulmonary ventilation and facilitated weaning from mechanical ventilation. 3. The mechanisms for the improvement in cardiopulmonary status following early dexamethasone therapy in MAS remain unclear. An overall improvement in cardiac hemodynamics, along with a significant decrease in lung inflammation may be responsible for the improvement." ]

[ "8434331", "3536770", "15014270", "15704503", "10851101", "10767815", "7849747", "9820916", "8484146", "12892241", "7895394", "15895329", "10327508", "11740347" ]

[ "Clinical trial of postoperative dynamic back exercises after first lumbar discectomy.", "Rehabilitation after surgery for lumbar disc herniation: results of a randomized clinical trial.", "Economic evaluation of a behavioral-graded activity program compared to physical therapy for patients following lumbar disc surgery.", "The effectiveness of exercise programmes after lumbar disc surgery: a randomized controlled study.", "Can exercise therapy improve the outcome of microdiscectomy?", "Early aggressive exercise for postoperative rehabilitation after discectomy.", "A randomized-control study of active and passive treatments for chronic low back pain following L5 laminectomy.", "Early active training after lumbar discectomy. A prospective, randomized, and controlled study.", "Intensive dynamic back exercises with or without hyperextension in chronic back pain after surgery for lumbar disc protrusion. A clinical trial.", "Efficacy of dynamic lumbar stabilization exercise in lumbar microdiscectomy.", "Supervised endurance exercise training compared to home training after first lumbar diskectomy: a clinical trial.", "Effects of home strength training and stretching versus stretching alone after lumbar disk surgery: a randomized study with a 1-year follow-up.", "Return to work after surgery for lumbar disc herniation. A rehabilitation-oriented approach in insurance medicine.", "Randomized controlled trial of neural mobilization after spinal surgery." ]

[ "Ninety-six patients who had undergone first-time discectomy for herniated lumbar intervertebral discs were consecutively randomized to two physical rehabilitation programs: a program of high-intensity, dynamic back extension and abdominal exercises with occurrence of low back pain being the limiting factor or a traditional program of mild, generally mobility-improving exercises within pain limits. Both groups underwent 14 hours of treatment during a 6-week period 5 weeks after surgery. At 26 weeks' follow-up, results indicated that patients who did the high-intensity exercises experienced greater success with regard to the patient disability-index and work capabilities. After 1 year, a trend that favored the use of intensive exercises could be observed. No differences were found in pain or objective measurements. A rehabilitation program of intensive exercises with occurrence of back pain being the limiting factor appears to increase patient behavioral support, resulting in work capacity improvements and patient self-rated disability levels. The results indicate that a 6-wk, 14-hr postoperative rehabilitation program is inadequate if objective postoperative deficit improvements are the desired goal.", "The aim of this prospective study was to examine the one-year postoperative results in patients operated on for lumbar disc herniation randomized in two groups: one with comprehensive rehabilitation and the other taken care of by normal care facilities. A total of 212 patients without any previous spinal operations comprised the final study group. The physiatrist, the surgeon, the social worker, and the psychologist performed the handicap evaluation according to the occupation handicap scales of the WHO. The handicap was evaluated for two phases: before the onset of acute sciatica leading to operation and one year after operation. No significant differences in handicap distribution between the intervention and normal care groups were seen. The postoperative handicap correlated highly significantly with preoperative handicap for both groups. More than half (57%) of all the patients returned to work within two months of the operation. The amount of sick leaves did not differ significantly between the intervention and normal care groups. A total of 15 persons (7%) retired during the postoperative year.", "An economic evaluation was conducted alongside a randomized controlled trial.\n Little is known about the effectiveness of cognitive-behavioral treatment options for patients following lumbar disc surgery. If the knowledge available was supported by an economic evaluation, the information could then be used to make recommendations for the implementation of cognitive-behavioral treatment in the routine of rehabilitation following lumbar disc surgery.\n To examine the cost-effectiveness of a behavioral-graded activity program, which is an operant treatment, compared to usual care as delivered by a physical therapist for patients following first-time lumbar disc surgery.\n For the economic evaluation, a societal viewpoint was applied. The primary outcome measures (measured at the 12-month follow-up) were global perceived effect and functional status. To evaluate the economic consequences of the treatments, direct health care and non-health care costs were considered, as well as indirect costs.\n The clinical outcomes showed no relevant differences between behavioral-graded activity (n = 52) and UC (n = 53). Treatment costs were almost identical in the two intervention groups. The difference in direct health care costs was, although not statistically significant, 264 EURO [95% CI: -3-525] higher in behavioral-graded activity than in usual care per patient-year. It was mainly the excess cost of visiting the physiotherapist in the behavioral-graded activity group that accounted for this difference. The difference in direct non-health care costs, although not statistically significant, was 388 EURO [95% CI: -217; 992] lower in the usual care group due to unpaid help by friends or family. Consequently, although again not statistically significant, the total direct costs in behavioral-graded activity are 639 EURO [95% CI: -91; 1368] higher than in usual care. For the indirect costs, there was a statistically significant difference, behavioral-graded activity being more expensive. The sensitivity analysis showed that these results are fairly robust.\n This study concludes that there are no differences between the two treatment conditions on any of the clinical outcome measures but that behavioral-graded activity is associated with higher costs. Consequently, there is no reason for the implementation of behavioral-graded activity as the standard treatment for patients following lumbar disc surgery.", "To compare two different exercise programmes versus a control group, after lumbar disc surgery.\n A prospective, single-blind, randomized controlled study.\n Outpatient clinic of Istanbul Faculty of Medicine, Department of Physical Medicine and Rehabilitation.\n Sixty patients diagnosed as having single level lumbar disc herniation with clinical examination and MRI evaluation and who had undergone lumbar discectomy (post-operative first month) at a single level. Patients with serious pathologies involving the cardiac and respiratory systems that could prevent them from doing exercises were excluded. Intervention: The patients were randomly split into three groups. The first group received an intensive exercise programme and back school education while the second group received a home exercise programme and back school education. The third group was defined as the control group and did not receive education or exercise.\n The patients were evaluated at the beginning and end of the treatment with clinical parameters, pain levels, endurance tests and weight-lifting tests, modified Oswestry Disability Index, Beck Depression Inventory, Low Back Pain Rating Scale and return to work.\n The groups doing exercises experienced a decrease in the severity of pain and disability, also functional parameters showed better improvement than the control group. The intensive exercise programme was better than the home exercise programme.\n It seems that intensive exercise is more effective in reduction of pain and disability, but whether it is cost-effective is not clear.", "A prospective randomized controlled trial of exercise therapy in patients who underwent microdiscectomy for prolapsed lumbar intervertebral disc. Results of a pilot study are presented.\n To determine the effects of a postoperative exercise program on pain, disability, psychological status, and spinal function.\n Microdiscectomy is often used successfully to treat prolapsed lumbar intervertebral disc. However, some patients do not have a good outcome and many continue to have low back pain. The reasons for this are unclear but impairment of back muscle function due to months of inactivity before surgery may be a contributing factor. A postoperative exercise program may improve outcome in such patients.\n Twenty patients who underwent lumbar microdiscectomy were randomized into EXERCISE and CONTROL groups. After surgery, all patients received normal postoperative care that included advice from a physiotherapist about exercise and a return to normal activities. Six weeks after surgery, patients in the EXERCISE group undertook a 4-week exercise program that concentrated on improving strength and endurance of the back and abdominal muscles and mobility of the spine and hips. Assessments of spinal function were performed in all patients during the week before surgery and at 6, 10, 26, and 52 weeks after. The assessment included measures of posture, hip and lumbar mobility, back muscle endurance capacity and electromyographic measures of back muscle fatigue. On each occasion, patients completed questionnaires inquiring about pain, disability and psychological status.\n Surgery improved pain, disability, back muscle endurance capacity and hip and lumbar mobility in both groups of patients. After the exercise program, the EXERCISE group showed further improvements in these measures and also in electromyographic measures of back muscle fatigability. All these improvements were maintained 12 months after surgery. The only further improvement showed by the CONTROL group between 6 and 52 weeks was an increase in back muscle endurance capacity.\n A 4-week postoperative exercise program can improve pain, disability, and spinal function inpatients who undergo microdiscectomy. [Key words: electromyogram median frequency, exercise therapy, intervertebral disc prolapse, microdiscectomy, randomized controlled trial, spinal function.", "A randomized clinical trial of postoperative medical exercise therapy in patients after operation for lumbar disc herniation with blind assessment of clinical outcomes.\n To assess the effect of an early regimen of vigorous medical exercise compared with an ordinary care program.\n \n Patients offered an operation for lumbar disc herniation were consecutively randomized to a training group or to a control group. The training consisted of an 8-week active rehabilitation program including a regimen of vigorous lumbar stabilizing exercises. The control subjects participated in a mild program of 2 to 3 back exercises at home, after relaxing and resting their backs for 2 months after the surgery. The outcomes were evaluated 6 and 12 months after the operation. The results are based on intention-to-treat analyses.\n Sixty-three of 65 eligible patients agreed to participate in the trial. Fifty-eight and 53 patients attended for evaluation at 6 and 12 months, respectively. There was a significantly larger improvement in the mean Roland's disability index (from 8.9 to 5.4 [P = 0.02] at 6 months and from 8. 7 to 5.3 [P = 0.03] at 12 months) and in reported pain (from 3.7 to 2.0 [P = 0.04] at 6 months and from 3.2 to 1.8 [P = 0.09] at 12 months) in the training group. A significantly (P = 0.05) higher proportion of the training group reported that they participated in daily activities as usual. There were more patients in the training group who reported improvement in self-evaluated health after surgery at both 6 (P = 0.02) and at 12 months (P = 0.05). Finally, no differences in clinical end points were observed between the groups.\n Vigorous medical exercise therapy, started 4 weeks after surgery for lumbar disc herniation, reduced disability and pain after surgery. Because no differences in clinical end points were observed, there is hardly any danger associated with early and vigorous training after operation for disc herniation.", "The professional literature contains relatively few randomized-control studies that have assessed the efficacy of physical therapy approaches to the management of patients with chronic low back pain (CLBP). The purposes of this study were: 1) to investigate the effects of physical agents, joint manipulation, low-tech exercise, and high-tech exercise on objective measures of CLBP; 2) to track the length of CLBP relief; and 3) to determine treatment cost-effectiveness. Two-hundred-fifty subjects (68 females, 182 males; ages 34-51 years) with CLBP following an L5 laminectomy were randomly assigned into five separate groups for a treatment period of 8 weeks. Chronic low back pain status was measured by modified-modified Schober, Cybex Liftask, and Oswestry procedures. Results revealed that: 1) only low-tech and high-tech exercise produced significant improvements (p < .05) in CLBP, 2) the mean period of CLBP relief ranged from 1.6 weeks (control) to 91.4 weeks (low-tech exercise), and 3) low-tech exercise was most cost-effective. It was concluded that: 1) low-tech and high-tech exercise were the only effective treatments for CLBP, 2) low-tech exercise produced the longest period of CLBP relief, and 3) low-tech exercise was the most cost-effective form of treatment. Clinically, low-tech exercise may be the treatment method of choice for the effective management of chronic low back pain.", "A prospective, randomized, and controlled study was conducted.\n To evaluate two training programs, both of which started immediately after lumbar discectomy.\n In previous studies, patients began physiotherapy between 4 weeks and 60 months after surgery. No studies have been conducted to evaluate a physiotherapy program that begins immediately after surgery.\n Twenty-six patients were treated according to an early active training program. Twenty-six patients were treated with a traditional, less active training program (control group). All patients were examined immediately before and after surgery and 3, 6, 12, and 52 weeks after surgery by an unbiased observer. Two years after surgery, patients completed a questionnaire. Range of motion of the lumbar spine and straight leg raising were measured. pain intensity and location was measured by a visual analog scale. The duration of sick leave was documented.\n Six and 12 weeks after surgery, patients with dominating residual leg pain had significantly less intense pain in the early active training group than those in the control group (P < 0.05). Twelve weeks after surgery, range of motion of the lumbar spine was significantly more increased in the early active training group (P < 0.01). One year after surgery, there was no significant difference between the groups regarding the duration of sick leave, results in a positive straight leg raising, or pain intensity. Twenty-two (88%) patients in the early active training group and 16 (67%) in the control group were satisfied with the treatment outcome 2 years after surgery (P < 0.10).\n Patients rehabilitated according to the early active training program had a better short-term outcome of objective values. At 2 years' follow-up, more patients were satisfied with the result of the operation. The early active treatment program is recommended.", "Sixty-two patients with chronic low back pain occurring 14-60 months after undergoing discectomy for the first time were randomized to two physical treatment groups: 24 sessions of intensive dynamic back exercises with hyperextension or 24 sessions of intensive dynamic back exercises without hyperextension. At the conclusion of therapy and at one-year follow-up, no difference was seen between the randomized groups, with regard to the combined assessments of pain, disability and objective measurements. A difference for back exercises without hyperextension to be superior to the other treatment regimen was statistically significant at the three-month follow-up. In the patient's qualitative assessment of treatment outcome there were seen no significant differences between back exercises with or without hyperextension. There was a similar and significant improvement of the isometric endurance of back muscles in both groups, but the flexibility of the spine was significantly improved only in the group using hyperextension exercises. The overall response rate of an earlier published investigation was reproduced. It is concluded that chronic back patients after first time discectomy may benefit from an intensive rehabilitation protocol including intensive exercises. The added use of hyperextension exercises does not confer any independent benefit. Furthermore, the training had to continue for more than 2-3 months before a statistical significant decrease in back pain was reported in the patient pain diary.", "The aim of this study was to determine the efficacy of dynamic lumbar stabilization exercises in patients with lumbar microdiscectomy.\n A prospective, randomized, controlled study.\n Forty-two patients who were diagnosed as having lumbar disc herniation and had been operated on using the microdiscectomy method were divided randomly into 3 groups.\n Dynamic lumbar stabilization exercises were set for the first group and a home exercise programme for the second. The third group given no exercises was considered as a control group. All patients were examined twice, once before the exercise programme and once 8 weeks later.\n Improvement in the first group was highly significant after the treatment (p < 0.0001). The second group improved significantly more in some parameters (pain, functional disability, lumbar Schober, progressive isoinertial lifting evaluation (neck), trunk endurance (flexion-extension)) than did the third group. The third group of patients showed some improvement in fingertip-floor distance, functional disability, modified lumbar Schober and left rotation in 8 weeks, but there were no significant improvements in the other parameters.\n Dynamic lumbar stabilization exercises are an efficient and useful technique in the rehabilitation of patients who have undergone microdiscectomy. They relieve pain, improve functional parameters and strengthen trunk, abdominal and low back muscles.", "We performed a randomised trial to evaluate if intensive supervised training of the back should be offered to all patients after a first lumbar diskectomy.\n Forty consecutive patients were, after a first lumbar diskectomy, randomly allocated to 2 groups undergoing \"supervised training\" twice a week for 3 months in an outpatient clinic or \"home training\" after 2 hours of instruction.\n The two rehabilitation models both showed a significant effect on spinal mobility, isokinetic trunk flexion strength, isokinetic trunk extension strength and daily function. These improvements were unchanged at follow up 3 months later. The pain score remained unchanged, however, throughout the trial in both groups. No differences in effect between the two rehabilitation models could be found for any of the assessed parameters. Thirteen patients did not complete the trial, including 9 from the supervised endurance trained group, mainly because of increased pain and reprolaps (n = 4). Four patients dropped out of the home trained group, only one because of increased pain. The differences in drop-out rate and training side effects were, however, not statistically significant.\n We conclude that it is not worthwhile to implement 3 months of supervised intensive endurance training as opposed to home training in all cases of first lumbar diskectomy, although a beneficial effect and better compliance might be found for a selected group of such patients.", "To assess the adherence to and effects of a 12-month combined strength and stretching home exercise regimen versus stretching alone, on patient outcome after lumbar disk surgery.\n Randomized controlled trial.\n Departments of physical medicine and rehabilitation and orthopedics at a Finnish hospital.\n Patients (N=126) were randomized into either a combined strength training and stretching group (STG, n=65) or a control group (CG, n=61).\n The STG was instructed to perform strength training and both the STG and CG were instructed in the same stretching and stabilization exercises for 12 months.\n Pain on the visual analog scale (VAS), the Oswestry and the Million disability indexes, isometric and dynamic trunk muscle strength, mobility in the lumbar spine, and straight-leg raising were measured.\n The trial was completed by 71% and 77% of the patients from the STG and the CG, respectively. The mean strength training frequency decreased from 1.5 to 0.6 times a week in the STG during the intervention. The mean stretching frequency decreased from 3.7 to 1.6 times a week in both groups. Median back and leg pain varied between 17 and 23 mm (VAS), and the Million and Oswestry indices varied between 14 and 23 points 2 months postoperatively. No statistically significant changes took place in these outcome measures during the 12-month follow-up in both groups. The changes in isometric trunk extension favored the STG ( P =.016) during the first 2 months. However, during the whole 12-month training period, both dynamic and isometric back extension and flexion strength, as well as mobility of the spine and repetitive squat-test results, improved significantly in both groups, and no differences were found in any of the physical function parameters between the STG and CG.\n At the 12-month follow-up, no statistically significant changes were found in the physical function, pain, or disability measures between the groups. In the STG, training adherence with regard to training frequency and intensity remained too low to lead to specific training-induced adaptations in the neuromuscular system. Progressive loading, supervision of training, and psychosocial support is needed in long-term rehabilitation programs to maintain patient motivation.", "An intervention study by the medical advisers of a social security sickness fund on a mandatorily insured patient population after open discectomy for herniated lumbar intervertebral disc. The medical advisers were randomized into two groups: a control group (n = 30) and an intervention group (n = 30).\n To compare a rehabilitation-oriented approach in insurance medicine focused primarily on early mobilization and early resumption of professional activities with the usual claim-based practice.\n This study included 710 patients, with a mean age of 39.2 years, who underwent surgery for herniated lumbar disc.\n Medical advisers in the rehabilitation-oriented group examined the patients monthly, starting at 6 weeks after the surgical intervention. They used a newly developed protocol to motivate the patients and treating physicians toward social and professional reintegration.\n At 52 weeks, 10.1% of the patients guided by medical advisers from the rehabilitation-oriented group had not resumed work in contrast to 18.1% of the patients in the control group. It was statistically proven that this effect also holds during the follow-up period.\n A rehabilitation-oriented approach by the medical advisers of social security can increase the probability of a return to work for patients after lumbar disc herniation surgery.", "Randomized controlled trial with 12-month follow-up.\n To determine whether the addition of neural mobilization to standard postoperative care improved the outcome of lumbar spinal surgery.\n It has been suggested that neural mobilization should be performed after spinal surgery to prevent nerve root adhesions and improve outcome. However, to date, there is no convincing evidence of the value of neural mobilization.\n Eighty-one patients undergoing lumbar discectomy, fusion, or laminectomy at a private hospital in Sydney were randomly allocated to standard postoperative care or standard care plus neural mobilization. Neural mobilization included passive movements and active exercises designed to mobilize the lumbosacral nerve roots and sciatic tract. Primary outcome measures were global perceived effect measured on a 7-point scale, pain measured using visual analogue scales and the McGill Pain Questionnaire, and disability measured with the Quebec Disability Scale.\n All patients received the treatment as allocated with 12-month follow-up data available for 76 patients (94% of those randomized). There were no statistically significant or clinically significant benefits provided by the neural mobilization treatment for any outcome.\n The neural mobilization protocol evaluated in this study did not provide an additional benefit to standard postoperative care for patients undergoing spinal surgery. The authors advocate that this protocol not be used in clinical practice." ]

[ "17534979", "22093120", "17596273" ]

[ "RhDNase before airway clearance therapy improves airway patency in children with CF.", "Timing of dornase alpha inhalation does not affect the efficacy of an airway clearance regimen in adults with cystic fibrosis: a randomised crossover trial.", "Recombinant human DNase nebulisation in children with cystic fibrosis: before bedtime or after waking up?" ]

[ "Little is known about the optimal timing of rhDNase nebulization in relation to airway clearance therapy (ACT).\n To compare the effects of rhDNase before ACT versus rhDNase after ACT in children with CF.\n Design: randomized, double blind, double dummy, cross over study. Inclusion criteria: CF, stable clinical condition, rhDNase maintenance therapy. Children in Group I inhaled rhDNase 30 minutes before ACT, and placebo directly after ACT in week 1-3. The protocol was reversed during week 4-6. Group II performed the reversed sequence. Patients continued their daily routine ACT. Primary endpoint: MEF(25) %pred. Pulmonary functions tests were performed on days 0, 14, 21, 35 and 42. In weeks 3 and 6 children scored cough and sputum production on daily diary cards.\n 24 patients completed the study. Mean age = 12 years (range 7-19). Mean MEF(25) %pred was 5.8% higher after 3 weeks of rhDNase before ACT, compared to rhDNase after ACT (58.3% vs 52.5%, p=0.01). There were no significant differences for any of the other variables.\n Inhalation of rhDNase before ACT improves peripheral airway patency in children with cystic fibrosis. Since all children were already on maintenance rhDNase therapy before the study, this effect is additional to any existing effect of regular rhDNase.", "Does the timing of inhalation of dornase alpha in relation to physical airway clearance techniques influence the effect of the entire airway clearance regimen?.\n A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinding of patients, therapists, and assessors.\n Twenty adults with cystic fibrosis who were not taking dornase alpha were recruited, of whom 17 were randomised and completed the trial.\n Participants performed an individually tailored session of physical airway clearance techniques for at least 15 minutes per day for 28 days. For 14 days, dornase alpha was inhaled before each session of airway clearance techniques and a placebo was inhaled after. For the other 14 days, placebo was inhaled before and dornase alpha after airway clearance techniques. The order of the two 14-day periods was randomised.\n The primary outcome was the forced expiratory volume in 1 sec (FEV(1)). Secondary outcomes were forced vital capacity, 24-hour sputum production, sputum production during the airway clearance regimen, oxygen saturation, peak oxygen consumption during an incremental exercise test, oxygen desaturation during exercise, and quality of life.\n Inhalation of dornase alpha after airway clearance techniques did not significantly affect the change in FEV(1) compared with inhalation before airway clearance techniques, mean difference 0.04 L, 95% CI -0.14 to 0.23. None of the secondary outcomes differed significantly between the study arms. There was good correlation between the change in FEV(1) and the change in quality of life scores.\n Timing of dornase alpha can be selected according to convenience, patient preference, or to accommodate the timing of other medications in the treatment regimen.\n ACTRN12611001041943.\n Copyright © 2011 Australian Physiotherapy Association. Published by .. All rights reserved.", "The present study focused on patients with cystic fibrosis (CF), who were on maintenance therapy with recombinant human deoxyribonuclease (rhDNase), with the aim of comparing efficacy and possible side effects of nebulisation of rhDNase when taken before bedtime with efficacy and side effects when taken after waking up. A randomised, double-blind, double-dummy, crossover study group was used. The inclusion criteria were as follows: 1) CF, 2) stable clinical condition and 3) rhDNase maintenance therapy. Patients in group I inhaled rhDNase before bedtime and a placebo after waking up in weeks 1-2. The protocol was reversed during weeks 3-4. Group II patients performed the reverse of this sequence. Patients continued with their daily routine sputum expectoration. The primary end-point was classified as the maximal instantaneous forced flow when 25% of the forced vital capacity remained to be exhaled (MEF(25%)). Pulmonary functions tests were performed on days 0, 7, 14, 21 and 28. At 1, 2, 3 and 4 weeks arterial oxygen saturation and cough frequency were measured during the night. A total of 24 patients completed the study. The mean (range) age of the patients was 13 (6-19) yrs. MEF(25%), taken to be the primary end-point, did not show a significant difference between nebulisation of rhDNase before bedtime compared with when taken after waking up. Nocturnal cough, oxygen saturation, and other secondary end-points were not significantly different between the two study periods. In conclusion, the present study found that it is equally effective and safe to nebulise recombinant human deoxyribonuclease before bedtime compared with when performed after waking up in children with cystic fibrosis, who are on maintenance treatment with recombinant human deoxyribonuclease." ]

[ "12603234", "15899686", "14667431", "10048112", "10181019", "11456079", "8223364", "11162323", "8543703", "11718591", "11570836", "16027567", "10446040", "11397745", "11162345", "18155287", "21432325", "8123347", "17995993", "15896835", "15367070", "15805374", "14672637", "15598198", "12795579", "14982550", "7971879", "12780372", "11817768", "9744123", "18804331", "18280668", "15533536", "7735003", "18236302", "15165654", "11194701", "15140462", "18304363" ]

[ "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.", "Evaluation of an intervention for hospitalized African American smokers.", "Size, consistency, and stability of stage effects for smoking cessation.", "Targeting smokers with low readiness to change with tailored and nontailored self-help materials.", "Long-term effectiveness of computer-generated tailored feedback in smoking cessation.", "Evaluating a population-based recruitment approach and a stage-based expert system intervention for smoking cessation.", "Standardized, individualized, interactive, and personalized self-help programs for smoking cessation.", "Counselor and stimulus control enhancements of a stage-matched expert system intervention for smokers in a managed care setting.", "A randomized trial of self-help materials, personalized feedback, and telephone counseling with nonvolunteer smokers.", "Effectiveness of a computer-tailored smoking cessation program: a randomized trial.", "The change-in-stage and updated smoking status results from a cluster-randomized trial of smoking prevention and cessation using the transtheoretical model among British adolescents.", "The effectiveness of a nursing inpatient smoking cessation program in individuals with cardiovascular disease.", "Evaluation of a minimal self-help smoking cessation intervention following cervical cancer screening.", "Cost effectiveness of computer tailored and non-tailored smoking cessation letters in general practice: randomised controlled trial.", "Effectiveness of a minimal contact smoking cessation program for Dutch general practitioners: a randomized controlled trial.", "Initial efficacy of MI, TTM tailoring and HRI's with multiple behaviors for employee health promotion.", "Effects of stage-matched repeated individual counseling on smoking cessation: A randomized controlled trial for the high-risk strategy by lifestyle modification (HISLIM) study.", "Randomized telephone smoking-intervention trial initially directed at blue-collar workers.", "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.", "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.", "Teen reach: outcomes from a randomized, controlled trial of a tobacco reduction program for teens seen in primary medical care.", "Long-term effects (up to 18 months) of a smoking cessation program among women smokers in public health clinics.", "Does stage-based smoking cessation advice in pregnancy result in long-term quitters? 18-month postpartum follow-up of a randomized controlled trial.", "Extended telephone counseling for smoking cessation: does content matter?", "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.", "One-to-one: a motivational intervention for resistant pregnant smokers.", "Effect of smoking cessation counseling on recovery from alcoholism: findings from a randomized community intervention trial.", "Smoking cessation and relapse prevention for postpartum women: results from a randomized controlled trial at 6, 12, 18 and 24 months.", "\"Look at your health\": outcomes associated with a computer-assisted smoking cessation counseling intervention for community college students.", "The TEAM project: the effectiveness of smoking cessation intervention with hospital patients.", "Feasibility and effectiveness of a stages-of-change model in cigarette smoking cessation counseling.", "Computer-tailored smoking cessation intervention in a general population setting in Germany: outcome of a randomized controlled trial.", "Training support persons to help smokers quit: a pilot study.", "Stages of change and smoking cessation: a computer-administered intervention program for young adults.", "Development and process evaluation of a web-based smoking cessation program for college smokers: innovative tool for education.", "Acceptability and effectiveness of opportunistic referral of smokers to telephone cessation advice from a nurse: a randomised trial in Australian general practice." ]

[ "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.", "To evaluate the effectiveness of a smoking cessation intervention based on the transtheoretical model of change with a sample of low-income African American smokers admitted to an indigent-care hospital.\n The intervention incorporated components shown to be effective in increasing cessation in other populations, tailored to a bedside counseling format with follow-up contact postdischarge.\n Intervention patients were significantly more likely to advance in stage than were control patients.\n A hospital-offered bedside intervention offers promise in reaching underserved smokers with effective, though limited, cessation assistance.", "In the transtheoretical model (TTM), the stage effect is one of the most important determinants of health behavior change. Randomly assigned to 1 of 11 treatment conditions were 4653 smokers. A total of 66 stage effects were possible with 6 for each of the 11 treatment groups. The results suggest that brief stage-matched interventions that help populations progress one stage could produce 75% more abstinence. Interventions that help populations progress two stages could produce 300% more abstinence. The results also support the importance of replicating the stage effects across treatment conditions and over time.", "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.", "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.", "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.", "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.", "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.", "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).", "From a public health perspective, prevention of cancer and cardiovascular diseases requires effective smoking cessation programs that can be used on a large scale.\n To test the effectiveness of a new computer-tailored smoking cessation program vs no intervention.\n Randomized controlled trial, in the French-speaking part of Switzerland, September 20, 1998, to December 31, 1999. Potential participants were randomly selected from a general population register and recruited by mail. Daily cigarette smokers who wished to participate (N = 2934) were randomized to either the program or no intervention. A mean of 1.5 times per 6 months, participants in the active arm received by mail a computer-tailored counseling letter based on their answers to a questionnaire and stage-matched booklets. The counseling letters were tailored to the participants' stage of change (categorized as precontemplation [no intention of quitting smoking in the next 6 months], contemplation [seriously considers quitting in the next 6 months], or preparation [has decided to quit in the next 30 days]), level of tobacco dependence, self-efficacy, and personal characteristics. The outcome measure was self-reported abstinence (no puff of tobacco smoke in the past 4 weeks) 7 months after entry into the program.\n Abstinence was 2.6 times greater in the intervention group than in the control group (5.8% vs 2.2%, P<.001). The program was effective in \"precontemplators\" who were not motivated to quit smoking at baseline (intervention vs control, 3.8% vs 0.8%; P =.001) and was effective regardless of perceived difficulty in quitting smoking at baseline.\n The program was effective in increasing smoking cessation rates. Because it can reach a large number of smokers, this program can substantially contribute to disease prevention at a population level.", "The transtheoretical model (TTM) and computer technology are promising technologies for changing health behavior, but there is little evidence of their effectiveness among adolescents.\n Four thousand two hundred twenty-seven Year 9 (ages 13-14) pupils in 26 schools were randomly allocated to control and 4,125 in 26 schools were allocated to TTM intervention. TTM pupils received three whole class lessons and three sessions with an interactive computer program. Control pupils received no special intervention. Positive change in stage and smoking status was assessed from a questionnaire completed at baseline, 1 year, and 2 years. Random effects logistic regression was used to compare the change in stage and smoking status between the arms.\n Eighty-nine percent of the TTM group and 89.3% of the control group were present at 1-year and 86.0 and 83.1%, respectively, were present at 2-year follow-up. The adjusted odds ratio (95% confidence interval) for positive stage movement in the TTM relative to control was 1.13 (0.91-1.41) at 1 year and 1.25 (0.95-1.64) at 2 years and for regular smoking was 1.14 (0.93-1.39) at 1 year and 1.06 (0.86-1.31) at 2 years. Subgroup analysis by initial smoking status revealed no benefit for prevention or cessation.\n The intervention was ineffective.\n Copyright 2001 American Health Foundation and Academic Press.", "Smoking is an important risk factor for cardiovascular disease (CVD), and quitting is highly beneficial. Yet, less than 30% of CVD patients stop smoking. Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease.\n A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change.\n Participants (N = 168) were randomly assigned by cohorts to inpatient counseling with telephone follow-up, inpatient counseling, and usual care. The inpatient intervention consisted of a 1-hr counseling session, and the telephone follow-up included 6 calls during the first 2 months after discharge. The nursing intervention was tailored to the individual's stage of change. End points at 2 and 6 months included actual and continuous smoking cessation rates (biochemical markers) and increased motivation (progress to ulterior stages of change).\n Assuming that surviving patients lost to follow-up were smokers, the 6-month smoking abstinence rate was 41.5% in the inpatient counseling with telephone follow-up group, compared with 30.2% and 20% in the inpatient counseling and usual care groups, respectively (p = .05). Progress to ulterior stages of change was 43.3%, 32.1%, and 18.2%, respectively (p = .02). Stage of change at baseline and intervention predicted smoking status at 6 months.\n This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months, and progression to ulterior stages of change. The telephone follow-up was an important adjunct. It is, therefore, recommended to include such comprehensive smoking cessation programs within hospital settings for individuals with CVD.", "This study was undertaken to evaluate a smoking cessation intervention provided to women smokers as follow-up to cervical cancer screening.\n Women who had had a Pap test in the prior month (N = 4,053) were called to complete a survey that assessed smoking status; 580 identified smokers were randomized to receive Usual care (n = 292) or a Self-help intervention (n = 288) that included a self-help booklet, a smoking and reproductive health information card, and three telephone counseling calls. Women were followed up at 6 and 15 months post-base line.\n Cessation rates in the Usual care (UC) and Self-help (SH) groups did not differ at the 6-month (UC 10.5% vs SH 10.9%, P = 0.56) or 15-month follow-up (UC 15.5% vs SH 10.6%, P = 0.17). Among women with an abnormal Pap test result there were no differences by study group in cessation rates at 6-month (UC 9.8% vs SH 11.0%, P = 0.71) or 15-month follow-up (UC 14.6% vs SH 13.4%, P = 0.96).\n Integrating interventions into the clinical setting and involving providers at the point of care may have greater potential for capitalizing on this \"teachable moment.\"\n Copyright 1999 American Health Foundation and Academic Press.", "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.", "Until recently, Dutch general practitioners contributed little to tobacco control. This is due to several factors, among which is the lack of a feasible intervention program for adult smokers. Such a minimal contact behavioral intervention, using the Stage-of-Change concept, is now available. Effectiveness was tested in a randomized trial.\n Twenty-two general practitioners and their practice assistants were trained in applying the program. In all, 530 smoking patients were enrolled, randomly assigned to either the intervention or the usual treatment condition. Analysis of treatment effects was performed with logistic regression analysis. In a backward stepwise procedure confounding effects of baseline differences were eliminated.\n At 12-month follow-up, self-reported abstinence rates (including nonrespondents as smokers) differed significantly between intervention subjects and controls: 13.4 vs 7.3% point prevalence (odds ratio 1.51, P < 0.05). An analysis of consecutive abstinence, defined as being abstinent at both 6- and 12-month follow-up, showed that 8.2% of the intervention group compared to 3.1% of the controls had sustained abstinence for more than 6 months (odds ratio 3.04, P < 0.001).\n Results indicate that an effective smoking cessation program for use in Dutch general practice, already shown to be feasible, is now available. Outcomes are generally consistent with recent international literature.\n Copyright 2001 American Health Foundation and Academic Press.", "This study was designed to compare the initial efficacy of Motivational Interviewing (MI), Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention (HRI) on four health risk factors (inactivity, BMI, stress and smoking) in a worksite sample.\n A randomized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments. The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months. At the initial post-treatment assessment at 6 months, groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks.\n Compared to the HRI only group, the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months. MI and TTM group outcomes were not different.\n This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes. Future research will examine the long-term impacts of each treatment, their cost effectiveness, effects on productivity and quality of life and process variables mediating outcomes.", "The purpose of this study was to evaluate the effects of stage-matched repeated individual behavioral counseling as an intervention for the cessation of smoking.\n We conducted a multisite randomized controlled trial that enrolled smokers unselected for their readiness to quit. There were 979 smokers with hypertension or hypercholesterolemia recruited from 72 study sites and randomly allocated to the intervention or control group. Smokers in the intervention group received stage-matched individual counseling consisting of a 40 minute initial session and four 20-30 minute follow-up sessions. Smokers in the control group received individual behavioral counseling for hypertension or hypercholesterolemia.\n The point prevalence abstinence rate at 6 months, validated by carbon monoxide testing, in the intervention group (13.6%) was 5.4 times higher (p<0.001) than that in the control group (2.5%). When the data were analyzed based on the baseline stage of change, there were significant differences in the abstinence rates at 6 months in smokers versus controls with each stage of change except in immotives. The odds ratio was 6.4 (p<0.001) in precontemplators, 6.7 (p<0.001) in contemplators, and 6.2 (p<0.01) in preparators. There was a positive, consistent effect of the intervention regardless of study site (worksite or community) or the presence of hypertension or hypercholesterolemia.\n We showed the effects of an intervention with repeated individual behavioral counseling on the cessation of smoking in smokers unselected for their readiness to quit. This result suggests that stage-matched individual counseling, based on the transtheoretical model, is effective in smokers with a lower motivation to quit as well as those ready to quit.", "Although smoking prevalence in the United States has declined markedly in recent years, prevalence among blue-collar workers remains high and few successful methods of reaching this group have been identified. The present study was designed to test the relative efficacy of two different approaches to telephone smoking-cessation counseling for blue-collar workers. Our study built on the experience of the National Cancer Institute's Cancer Information Service (CIS) and compared the past CIS smoking-cessation counseling procedure and a modified version of the present procedure. In our trial, callers to a special telephone hotline who asked for information on smoking cessation were randomly assigned to receive counseling under one of two protocols: 1) the past CIS procedure, in which general information was given and cessation materials were sent to the callers, and 2) a version of the present CIS stage-model procedure, adapted by us for use with blue-collar workers, in which callers were given counseling specific to their stage in the smoking-cessation process. The general-information group contained 185 subjects; the stage-model group contained 197. Despite extensive efforts in the present study, it was not possible to recruit the number of blue-collar workers planned for our statistical analysis. Consequently, of a total of 382 subjects recruited, 93 (24.3%) were blue-collar workers, 181 (47.4%) were white-collar workers, and 108 (28.3%) were retired persons who worked part time, student workers, or the unemployed. Our results show no statistically significant differences in either short-term or long-term nonsmoking rates between the general-information group and the stage-model group.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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)", "To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care.\n Both smoking and nonsmoking teens, 14 to 17 years of age, who were being seen for routine visits were eligible for this 2-arm controlled trial. Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group-practice health maintenance organization. Of 3747 teens invited at > or =1 visits, 2526 (67%) consented and were randomized to tobacco intervention or brief dietary advice. The tobacco intervention was individually tailored on the basis of smoking status and stage of change. It included a 30-second clinician advice message, a 10-minute interactive computer program, a 5-minute motivational interview, and up to two 10-minute telephone or in-person booster sessions. The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables. Follow-up smoking status was assessed after 1 and 2 years.\n Abstinence rates after 2 years were significantly higher for the tobacco intervention arm, relative to the control group, in the combined sample of baseline smokers and nonsmokers (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.03-1.47). Treatment effects were particularly strong among baseline self-described smokers (OR: 2.42; 95% CI: 1.40-4.16) but were not significant for baseline nonsmokers (OR: 1.25; 95% CI: 0.97-1.61) or for those who had \"experimented\" in the past month at baseline (OR: 0.95; 95% CI: 0.45-1.98).\n Brief, computer-assisted, tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset.", "We conducted longitudinal analysis of long-term outcomes of a motivational smoking cessation program. The program consisted of clinic-based minimal interventions delivered to women smokers in public health clinics by clinic personnel, a reminder letter, and an optional brief telephone counseling.\n Subjects seen in six intervention (N=541) and six control clinics (N=527) were interviewed by telephone 2, 6, 12, and 18 months later. At each measurement point, unadjusted percent abstinence and mean action, motivation, and readiness scores by study group were compared with standard bivariate comparisons tests. Hierarchical linear modeling that adjusted for clustering of subjects within clinics and clustering of results over 18 months (four waves) within individuals was used to compare outcomes by study group.\n Number of actions toward quitting, motivation, and stage of readiness to quit remained better in the intervention than in the control group up to 18 months. The program effect on abstinence was still significant at 12 months, but not at 18 months.\n Exposure to one-time, brief interventions in public health clinics appears sufficient to enhance abstinence up to 12 months, and action toward quitting and motivation and readiness to quit up to 18 months.", "To evaluate the effect on quitting smoking at 18 months postpartum of smoking cessation interventions based on the Transtheoretical Model (TTM) delivered in pregnancy compared to current standard care. It has been claimed that TTM-based interventions will continue to create quitters after the end of the intervention period.\n Cluster randomized trial.\n Antenatal clinics in general practices in the West Midlands, UK.\n A total of 918 pregnant smokers originally enrolled in the trial, of which 393 women were followed-up at 18 months postpartum.\n One hundred general practices were randomized into the three trial arms. Midwives in these practices delivered three interventions: A (standard care), B (TTM-based self-help manuals) and C (TTM-based self-help manuals plus sessions with an interactive computer program giving individualized smoking cessation advice).\n Self-reported continuous and point prevalence abstinence since pregnancy.\n When combined together, there was a slight and not significant benefit for both TTM arms compared to the control, with an odds ratio (OR) 95% confidence interval (CI) of 1.20 (0.29-4.88) for continuous abstinence. For point prevalence abstinence, the OR (95%CI) was 1.15 (0.66-2.03). Seven of the 54 (13%) women who had quit at the end of pregnancy were still quit 18 months later, and there was no evidence that the TTM-based interventions were superior in preventing relapse.\n The TTM-based interventions may have shown some evidence of a short-term benefit for quitting in pregnancy but no benefit relative to standard care when followed-up in the longer-term.", "Telephone counseling is a popular modality for smoking cessation treatment; however, little attention has been paid to evaluating the efficacy of different contents of calls. This study compared 2 types of proactive telephone calls following a group program. Participants were randomized to receive either: (a) basic content, consisting primarily of support; or (b) enhanced content, tailored to the stage of cessation (still smoking, abstinent, or relapsed) and targeting factors hypothesized to be related to success (motivation, self-efficacy, and negative mood). There was a significant interaction between treatment condition and gender. For men, the enhanced condition produced better abstinence rates through 15 months and lower relapse rates. For women, the basic condition was better. History of depression did not interact with condition.", "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.", "The purpose of this prospective, randomized controlled study was to determine the efficacy of an intensified, late pregnancy, smoking cessation intervention for resistant pregnant smokers (n = 269). Participants received 3-5 min of counseling plus a self-help booklet at their first prenatal visit and seven booklets mailed weekly thereafter; at 28 weeks, all had been smoking in the past 28 days. The experimental group received a stage of change-based, personalized feedback letter and two telephone counseling calls using Motivational Interviewing (MI) strategies. The control group received care as usual. The 34th week cotinine data demonstrated no overall difference between groups. However, an implementation analysis suggested that 43% of women who received the full intervention (E2) were classified as not smoking compared to 34% of the control group. At 6 weeks postpartum, 27.1% of the E2 group reported being abstinent or light smokers vs. 14.6% of the controls. No differences were detected at 3 and 6 months postpartum. Results lend preliminary but very modest support for this intervention with resistant pregnant smokers. Improvements in the intervention and implementation issues are discussed.", "To assess the effects of a smoking cessation program for recovering alcoholics on use of alcohol, tobacco and illicit drugs after discharge from residential treatment.\n A randomized community intervention trial design was employed in which 12 residential drug treatment centers in Iowa, Kansas and Nebraska were matched and then randomly assigned to the intervention or control condition.\n Approximately 50 adult residents (inpatients) from each site were followed for 12 months after treatment discharge.\n Participating residents in the six intervention centers received a 4-part, individually tailored, smoking cessation program while those in the six control sites received usual care.\n Both moderate and heavy drinking rates were reduced in the intervention group. Intervention site participants were significantly more likely than controls to report alcohol abstinence at both the 6-month (OR = 1.59, 95%CI: 1.09-2.35) and 12-month assessment (OR = 1.84, 95%CI: 1.28-2.92). Illicit drug use rates were comparable. Effect of the intervention on tobacco quit rates was not statistically significant.\n Counseling alcoholics in treatment to quit smoking does not jeopardize the alcohol recovery process. However, low-intensity tobacco interventions are unlikely to yield high tobacco quit rates.", "To test the efficacy of an aid to cessation/relapse prevention intervention for women postpartum.\n Two-armed randomized controlled trial. Follow-ups at 6, 12, 18, and 24 months, screenings on maternity wards. Intervention group received face-to-face counseling 40 days postpartum plus telephone counseling calls 4 and 12 weeks later. Control group received usual care plus self-help material for each parent.\n With regard to smoking cessation, 4 week point prevalence abstinent rates were higher in the treatment group at 6, 12, and 18 months (7% vs. 1%, 7% vs. 2%, and 9% vs. 1%, respectively). Sustained abstinence was higher in the treatment group at 6 months follow-up (3% vs. 0%). No difference was observed with regard to relapse prevention.\n Regarding aid to cessation we observed small effects, regarding relapse prevention no effect. In order to capitalize on the opportunity childbirth poses with regard to smoking, theories on relapse prevention in smoking cessation that guide in designing interventions are needed.", "Community college students represent 44% of all students enrolled in U.S. higher education facilities. To our knowledge, no previous smoking cessation intervention has targeted community college students. Previous studies suggest that a motivational smoking cessation intervention could be successful for young adult smokers. Combining motivational interviewing sessions with personalized health feedback is likely to increase participants' motivation to quit and movement through the stages of change. The purpose of this study was to evaluate the impact of a smoking cessation program based on these premises. We designed a computer-assisted, counselor-delivered smoking cessation program that addresses personal health risks and readiness to change smoking behavior among community college students. A group-randomized, controlled trial was used to assess the intervention in a sample of 426 students (58.5% females; mean age, 22.8+/-4.7 years) from 15 pair-matched campuses. At the 10-month follow-up assessment, the cotinine-validated smoking cessation rates were 16.6% in the experimental condition and 10.1% in the standard care condition (p=0.07). Our results indicate that our computer-assisted intervention holds considerable promise in reducing smoking among community college students.", "This study evaluated the effectiveness of three smoking cessation interventions for this population: (1) modified usual care (UC); (2) brief advice (A); and (3) brief advice plus more extended counseling during and after hospitalization (A + C).\n Smokers (2,095) who were in-patients in four hospitals were randomly assigned to condition. Smoking status was ascertained via phone interview 7 days and 12 months post-discharge. At 12 months, reports of abstinence were validated by analysis of saliva cotinine. Intent to treat analyses were performed.\n At 7-day follow-up, 24.2% of participants reported abstinence in the previous 7 days. There were no differences between conditions. At 12-month follow-up, self-reported abstinence was significantly higher in the A + C condition (UC (15.0%) vs. A (15.2%) vs. A + C (19.8%)). There was no significant difference among conditions in cotinine-validated abstinence, however (UC (8.8%) vs. A (10.0%) vs. A + C (9.9%)).\n These interventions for hospital in-patients did not increase abstinence rates. Features of the study that might have contributed to this finding were the inclusiveness of the participation criteria, the fact that pharmacological aids were not provided, and a stage-matching approach that resulted in less intensive counseling for participants unwilling to set a quit date.", "Counseling coupled with a stages-of-change model in cigarette smoking cessation is a useful method for physicians to help patients stop smoking. The participants were 27 physicians, randomly assigned to three groups of nine physicians each. The first group of physicians were given two lectures on the stages-of-change model on which to base their patient counseling. The second group of physicians were not exposed to the model but a reminder reading \"Ask your patients to stop smoking\" was placed in their clinic. The third group of physicians were neither exposed to the model nor given any reminder. Of the 93 smokers among the patients of the 27 physicians, 39 were in the first group, 26 in the second, and 28 in the third. A survey indicated that among the three groups there was no significant difference in demographic data, cigarette smoking history, and personal attitude toward smoking cessation counseling. At the end of six months, the first group of patients accomplished a quit smoking rate of 28.6%; of the patients still smoking 56% had decreased their daily cigarette consumption. The corresponding figures for the second group were 8.3% and 9.1%. The corresponding figures for the third group were 4.3% and 13.6%. These data show that counseling coupled with the concept of a stages-of-change model is feasible and effective to assist with cigarette smoking cessation.", "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.", "Evaluate the feasibility, acceptability, and potential efficacy of a skills-training intervention for adults interested in helping someone to stop smoking (i.e., support persons).\n Sixty adult support persons (77% female) were directly recruited from the community and randomly assigned to this intervention (manual plus five weekly group-based sessions) or a control condition (one-page leaflet). All intervention and outcome assessments occurred through the support persons. Assessments occurred at weeks 0 (baseline), 6 (end of treatment), 12, and 24. The study was conducted from 1998 to 2001; data collection occurred from 1999 to 2000. Outcomes were ratings of treatment acceptability, recruitment and retention rates, supportive behaviors provided to the smoker, and smoking behavior change in the smoker as reported by the support person.\n Support persons were recruited in a timely manner and study retention rates were high. Support persons in skills training showed significant increases in their supportive behavior scores compared with control subjects at weeks 6 and 12. Although not statistically significant, the skills-training intervention was associated with more quit attempts, greater improvement in stage of change, and higher 7-day point prevalence abstinence rates in the smokers than the control condition.\n A skills training intervention for support persons is feasible and acceptable. Further studies are needed to test the efficacy of this approach for smoking cessation.", "Sixty-five college-student smokers were randomly assigned to a four-week computer-administered, stage-based smoking control program or a four-week computer-administered general health education control condition. At post-test, the percentage of students advancing to a higher stage of readiness to change was slightly higher among those in the stage-based program compared to the control condition. At seven month follow-up, both groups reported abstinence rates of approximately 30%. Continuous abstinence for 6 months was 19% for the stage-based group and 14% for the control group at the final follow-up.", "Smoking cessation interventions are needed for young adults. Innovative approaches to behavior change for this population should be tested. Formative research and process evaluation of those approaches would result in more effective programs. This paper presents the development process and process evaluation of a web-based smoking cessation program. A description of the stages of development is presented with formative research, development of the web-based intervention, formative evaluation, and process evaluation. The smokers reported high usage of the intervention and satisfaction with the intervention in that it helped to raise their consciousness about quitting, encouraged them to set behavioral goals, provided stages of change feedback, and offered interactivity in presenting information and strategies about quitting. The Internet may be a promising tool for patient education according to the process results.", "GPs often lack time to provide intensive cessation advice for patients who smoke. This study aimed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse.\n Adult smokers (n = 318) attending 30 GPs in South Western Sydney, Australia were randomly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice, written information and follow-up delivered by a nurse. Self-reported point prevalence abstinence at six and 12 months was compared between groups. Characteristics of patients who accepted and completed the intervention were investigated.\n Of 169 smokers randomised to the intervention, 76 (45%) consented to referral. Compared with smokers in 'pre-contemplation', those further along the stage-of-change continuum were significantly more likely to consent (p = 0.003). Those further along the continuum also were significantly more likely to complete all four calls of the intervention (OR 2.6, 95% CI: 0.8-8.1 and OR 8.6, 95% CI: 1.7-44.4 for 'contemplation' and 'preparation' respectively). At six months, there was no significant difference between groups in point prevalence abstinence (intention to treat) (9% versus 8%, p = 0.7). There was no evidence of differential intervention effectiveness by baseline stage-of-change (p = 0.6) or patient sex (p = 0.5). At 12 months, point prevalence abstinence in the intervention and control groups was 8% and 6% respectively (p = 0.6).\n Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low. This trial did not demonstrate improved quit rates following the intervention. Future research efforts might better focus support for those patients who are motivated to quit. AUSTRALIAN CLINICAL TRIALS REGISTRY NUMBER: ACTRN012607000091404." ]

[ "6102677" ]

[ "Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Report of the Second Neonatal Meningitis Cooperative Study Group." ]

[ "In a multicentre controlled trial in the U.S.A. and Latin America 52 infants with meningitis and ventriculitis were randomly assigned to receive either systemic ampicillin and gentamicin or intraventricular gentamicin plus systemic antimicrobial agents. The aetiological agents most often encountered were Escherichia coli in the U.S. infants and Salmonella spp. in Latin American infants. Infants receiving systemic antibiotics plus intraventricular gentamicin had a significantly higher mortality rate (42.9%) than those who received systemic therapy only (12.5%). Duration of positive CSF cultures and morbidity rates were not significantly different in the two treatment groups. The concentrations of gentamicin in ventricular and lumbar CSF 1--6 h after an intraventricular dose of 2.5 mg gentamicin were 10--130 microgram/ml and 8--85 microgram/ml, respectively. The study was terminated early because of the higher mortality rate in the intraventricular-therapy group. Intraventricular gentamicin should not be used as routine treatment for neonatal meningitis caused by gram-negative enteric bacilli." ]

[ "10867086", "17767899", "12707240", "8360063", "12031725", "12370553", "16924183", "15951880", "6478567", "17196274" ]

[ "Program participation, exercise adherence, cardiovascular outcomes, and program cost of traditional versus modified cardiac rehabilitation.", "The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Home-based compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.", "Improved exercise tolerance and quality of life with cardiac rehabilitation of older patients after myocardial infarction: results of a randomized, controlled trial.", "Alternatives for cardiac rehabilitation patients unable to return to a hospital-based program.", "Effectiveness of three models for comprehensive cardiovascular disease risk reduction.", "A controlled trial of hospital versus home-based exercise in cardiac patients.", "Cardiac rehabilitation vs. home exercise after coronary artery bypass graft surgery: a comparison of heart rate recovery.", "Comparison of supervised exercise training and home-based exercise training in chronic heart failure.", "Home versus group exercise training for increasing functional capacity after myocardial infarction.", "Home-based versus hospital-based rehabilitation after myocardial infarction: A randomized trial with preference arms--Cornwall Heart Attack Rehabilitation Management Study (CHARMS)." ]

[ "Common concerns with the traditional protocol (TP) for cardiac rehabilitation include suboptimal program participation, poor facilitation of independent exercise, the use of costly continuous electrocardiographic (ECG) monitoring, and lack of insurance reimbursement. To address these concerns, a reduced cost-modified protocol (MP) was developed to promote independent exercise. Eighty low- to moderate-risk cardiac patients were randomized to a TP (n = 42) or a MP (n = 38) and were compared over 6 months on program participation, exercise adherence, cardiovascular outcomes, and program costs. During month 1, patients followed identical regimens, including 3 ECG-monitored exercise sessions/week, with encouragement to achieve >/=5 thirty-minute sessions/week. In week 5, the TP continued with a facility-based regimen including 3 exercise sessions/week for 6 months and used ECG monitoring the initial 3 months. The MP discontinued ECG monitoring in week 5 and were gradually weaned to an off-site exercise regimen that was complemented with educational support meetings and telephone follow-up. Compared with TP patients, MP patients had higher rates of off-site exercise over 6 months (p = 0.05), and total exercise (on site + off site) during the final 3 months (p = 0.03). Also, MP patients were less likely to drop out (p = 0.05). Both protocols promoted comparable improvements in maximal oxygen uptake (p <0.05), blood lipids (p <0.001), and hemodynamic measurements (p <0.002). The MP cost $738 less/patient than the TP and required 30% less staff (full-time equivalents). These results suggest that a reduced cost MP was as effective as an established TP in improving physiologic outcomes while demonstrating higher rates of exercise adherence and program participation. Thus, the MP or a similar protocol has applicability to hospitals with large capitated or managed care populations to provide cost-effective cardiovascular risk reduction to patients.", "To evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes.\n An individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes.\n Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002.\n A total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks.\n All the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English.\n Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks.\n No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost 198 pounds versus 157 pounds for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to 182 pounds. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual.\n A home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term.", "Whether cardiac rehabilitation (CR) is effective in patients older than 75 years, who have been excluded from most trials, remains unclear. We enrolled patients 46 to 86 years old in a randomized trial and assessed the effects of 2 months of post-myocardial infarction (MI) CR on total work capacity (TWC, in kilograms per meter) and health-related quality of life (HRQL).\n Of 773 screened patients, 270 without cardiac failure, dementia, disability, or contraindications to exercise were randomized to outpatient, hospital-based CR (Hosp-CR), home-based CR (Home-CR), or no CR within 3 predefined age groups (middle-aged, 45 to 65 years; old, 66 to 75 years; and very old, >75 years) of 90 patients each. TWC and HRQL were determined with cycle ergometry and Sickness Impact Profile at baseline, after CR, and 6 and 12 months later. Within each age group, TWC improved with Hosp-CR and Home-CR and was unchanged with no CR. The improvement was similar in middle-aged and old persons but smaller, although still significant, in very old patients. TWC reverted toward baseline by 12 months with Hosp-CR but not with Home-CR. HRQL improved in middle-aged and old CR and control patients but only with CR in very old patients. Complications were similar across treatment and age groups. Costs were lower for Home-CR than for Hosp-CR.\n Post-MI Hosp-CR and Home-CR are similarly effective in the short term and improve TWC and HRQL in each age group. However, with lower costs and more prolonged positive effects, Home-CR may be the treatment of choice in low-risk older patients.", "To determine the effectiveness of a home exercise program using transtelephonic exercise monitoring (TEM).\n Prospective, two-group experimental, random assignment.\n Urban centered hospital and surrounding community.\n Twenty cardiac rehabilitation patients entering a Phase II cardiac rehabilitation program.\n Maximal oxygen consumption, blood pressure, pressure-rate product, workload.\n Twenty male cardiac patients were randomly enrolled in either a 12-week home- or hospital-based exercise program. Maximal exercise tolerance tests were conducted, before and after exercise intervention, on a computer-driven bicycle ergometer. Subjects trained 3 days per week for 12 weeks on a bicycle ergometer for a maximum of 35 minutes at 75% of maximum heart rate reserve or functional capacity.\n Posttraining results showed significant improvement in cardiac function for both groups. Two patients in the TEM group developed new arrhythmias while exercising that required medication changes; however, no medical emergencies arose in either exercise group. Independent Student t test showed no significant difference between groups before or after training.\n We conclude that TEM is an effective alternative for the rehabilitation of patients who are unable to return to a hospital-based program.", "Cost and accessibility contribute to low participation rates in phase 2 cardiac rehabilitation programs in the United States. In this study, we compared the clinical effectiveness of 2 less costly and potentially more accessible approaches to cardiovascular risk reduction with that of a contemporary phase 2 cardiac rehabilitation program. Low- or moderate-risk patients (n = 155) with coronary artery disease (CAD) were randomly assigned to 12 weeks of participation in a contemporary phase 2 cardiac rehabilitation program (n = 52), a physician supervised, nurse-case-managed cardiovascular risk reduction program (n = 54), or a community-based cardiovascular risk reduction program administered by exercise physiologists guided by a computerized participant management system based on national clinical guidelines (n = 49). In all, 142 patients (91.6%) completed testing at baseline and after 12 weeks of intervention. For patients with abnormal (i.e., not at the goal level) baseline values, statistically significant (p < or =0.05) improvements were observed with all 3 interventions for multiple CAD risk factors. No statistically significant risk factor differences were observed among the 3 programs. For patients with a baseline maximal oxygen uptake < 7 metabolic equivalents, cardiorespiratory fitness increased to a greater degree in patients in the cardiac rehabilitation program and the community-based program versus the physician-supervised, nurse- case-managed program. These data have important implications for cost containment and increasing accessibility to clinically effective comprehensive cardiovascular risk reduction services in low- or moderate-risk patients with CAD.", "Large numbers of patients who stand to benefit from the exercise training component of cardiac rehabilitation are not being served due to access issues. Home-based exercise training may be a potentially useful alternative to training in institutional environments.\n The purpose of this study was to examine the benefit of 6 months of hospital-based exercise training versus 6 months of monitored, home-based exercise training with respect to physical, quality of life, and social support outcomes in patients after coronary artery bypass graft (CABG) surgery.\n Randomized controlled trial of \"direct-to-home\" (Home; = 120) versus \"direct-to-hospital\" (Hosp; = 122) exercise training, 35-49 d post CABG surgery. The primary outcome was peak exercise capacity, measured by peak oxygen consumption (VO(2)) on a symptom-limited cycle ergometer exercise test. Secondary outcomes were health-related quality of life (measured by the SF-36) and social support (measured by the ISEL). Measurements were taken at baseline and after 3 and 6 months of exercise training.\n The study groups had similar demographic and health profiles at baseline. Peak VO(2) improved significantly in both groups after 6 months of exercise training; 36% in the Hosp group (1,222.1 +/- 269.0 mL x min(-1) to 1,497.2 +/- 594.3 mL x min(-1); < 0.0001) and 31% in the Home group (1,260.3 +/- 306.5 mL x min(-1) to 1,433.4 +/- 589.7 mL x min(-1); < 0.05). The Home group reported greater total social support than the Hosp group at 3 (36.2 +/- 4.5 vs 34.0 +/- 6.7; < 0.0001) and 6 months (36.0 +/- 4.9 vs 34.6 +/- 6.4; = 0.05). The Home group demonstrated a greater improvement in health-related quality of life (physical) by 6 months in comparison to the Hosp patients (51.2 +/- 6.4 vs 48.6 +/- 7.1; = 0.004).\n This study suggests that low-risk CABG surgery patients may be served as well or better with a monitored, home-based exercise program than with an institution-based program.", "The autonomic dysfunction is known to adversely affect clinical outcome in patients with cardiovascular disease, and exercise training has been shown to modify the sympathovagal control of heart rate. The purposes of this study were to investigate the effect of cardiac rehabilitation on heart rate recovery in patients who received coronary artery bypass grafting (CABG) and compare the effect with that of a home-based exercise program.\n Fifty-four male patients having undergone CABG were randomly assigned to a cardiac rehabilitation exercise program (n = 18), a home-based exercise program (n = 18), and a control group (n = 18) for 12 wks to evaluate the differences in heart rate recovery among groups.\n Patients in the cardiac rehabilitation group had significant increases in heart rate recovery (19.1 +/- 6.2 vs. 14.0 +/- 5.4 beats/min, P = 0.022) compared with those in the control group. There were no significant differences in heart rate recovery between cardiac rehabilitation and home-based exercise groups (16.2 +/- 4.8 beats/min) or between home-based exercise and control groups. All three groups had significantly improved heart rate recovery compared with their baseline data (P < 0.001, < 0.001, and 0.007).\n Our results point out that a cardiac rehabilitation exercise program has a positive effect on heart rate recovery in patients having undergone CABG and is consistent with the autonomic improvement. Although the home-based exercise group did not reveal statistical significances over those in the control group, it had comparable efficacy to that demonstrated in the cardiac rehabilitation group.", "This study was planned to compare the outcomes between supervised and home-based exercise training in patients with chronic heart failure.\n The study was conducted at the Department of Physical Therapy in Ankara University, Faculty of Medicine, Turkey between 2000 and 2001. Twenty-two patients with stable chronic heart failure were randomly assigned to the supervised exercise training group (n=11) or the home-based exercise training group (n=11). Symptom-limited maximal exercise tests with gas exchange analysis were carried out before randomization. Work load equivalent to 60% of achieved peak heart rate at the tests was determined as exercise training work load for each subject. Both groups participated in a program of 3 exercise training sessions per week for 3 months. The exercise tests were repeated after 3 months.\n After training, peak exercise duration increased significantly in the supervised exercise training group and the home-based exercise training group (p<0.05). There was substantial improvement in peak VO2 with exercise training in the supervised exercise training group (p<0.05) but, peak VO2 did not change significantly in the home-based exercise training group (p>0.05).\n Supervised and home-based exercise training enhanced exercise capacity in patients with chronic heart failure. The training program must be tailored to each patient's specific limitations, individual needs and possibilities. Home-based exercise training may be a training alternative to stable chronic heart failure patients who prefer not to participate in an outpatient supervised training program.", "To evaluate the efficacy of exercise training for increasing functional capacity in the 6 months after clinically uncomplicated myocardial infarction, 198 men 52 +/- 9 years of age participated in a training study. They were randomly assigned to one of four exercise protocols: 8 to 26 weeks of training at home (group 1, n = 66) or in a group program (group 2, n = 61) following treadmill testing performed 3 weeks after infarction, treadmill testing at 3 weeks without subsequent training (group 3, n = 34), and treadmill testing for the first time at 26 weeks (control, n = 37). At 26 weeks functional capacity was significantly higher in patients training at home or in a group program than that in patients without training or in control patients: 8.1 +/- 1.5, 8.5 +/- 1.3, 7.5 +/- 1.8, and 7.0 +/- 1.7 METs, respectively (p less than .05 and p less than .001). No significant differences in functional capacity were noted between patients training at home and those in a group program. No training-related complications occurred. Home and group training are equally effective in increasing functional capacity of low-risk patients after myocardial infarction.", "Participation in cardiac rehabilitation after acute myocardial infarction is sub-optimal. Offering home-based rehabilitation may improve uptake. We report the first randomized study of cardiac rehabilitation to include patient preference.\n To compare the clinical effectiveness of a home-based rehabilitation with hospital-based rehabilitation after myocardial infarction and to determine whether patient choice affects clinical outcomes.\n Pragmatic randomized controlled trial with patient preference arms.\n Rural South West England.\n Patients admitted with uncomplicated myocardial infarction were offered hospital-based rehabilitation classes over 8-10 weeks or a self-help package of six weeks' duration (the Heart Manual) supported by a nurse. Primary outcomes at 9 months were mean depression and anxiety scores on the Hospital Anxiety Depression scale, quality of life after myocardial infarction (MacNew) score and serum total cholesterol.\n Of the 230 patients who agreed to participate, 104 (45%) consented to randomization and 126 (55%) chose their rehabilitation programme. Nine month follow-up data were available for 84/104 (81%) randomized and 100/126 (79%) preference patients. At follow-up no difference was seen in the change in mean depression scores between the randomized home and hospital-based groups (mean difference: 0; 95% confidence interval, -1.12 to 1.12) nor mean anxiety score (-0.07; -1.42 to 1.28), mean global MacNew score (0.14; -0.35 to 0.62) and mean total cholesterol levels (-0.18; -0.62 to 0.27). Neither were there any significant differences in outcomes between the preference groups.\n Home-based cardiac rehabilitation with the Heart Manual was as effective as hospital-based rehabilitation for patients after myocardial infarction. Choosing a rehabilitation programme did not significantly affect clinical outcomes." ]

[ "12770957", "21141016", "16272048" ]

[ "Extracapsular cataract surgery compared with manual small incision cataract surgery in community eye care setting in western India: a randomised controlled trial.", "Visual outcome of conventional extracapsular cataract extraction with posterior chamber intraocular lens implantation versus manual small-incision cataract surgery.", "Comparison of endothelial cell loss and surgically induced astigmatism following conventional extracapsular cataract surgery, manual small-incision surgery and phacoemulsification." ]

[ "To study \"manual small incision cataract surgery (MSICS)\" for the rehabilitation of cataract visually impaired and blind patients in community based, high volume, eye hospital setting; to compare the safety and effectiveness of MSICS with conventional extracapsular cataract surgery (ECCE).\n In a single masked randomised controlled clinical trial, 741 patients, aged 40-90 years, with operable cataract were randomly assigned to receive either MSICS or ECCE and operated upon by one of eight participating surgeons. Intraoperative and postoperative complications were graded and scored according to the Oxford Cataract Treatment and Evaluation Team recommendations. The patients were followed up at 1 week, 6 weeks, and 1 year after surgery and their visual acuity recorded.\n This paper reports outcomes at 1 and 6 weeks. 706 of the 741(95.3%) patients completed the 6 week follow up. 135 of 362 (37.3%) of ECCE group and 165 of 344 (47.9%) of MSICS group had uncorrected visual acuity of 6/18 or better after 6 weeks of follow up. 314 of 362 (86.7%) of ECCE group and 309 of 344 (89.8%) of MSICS group had corrected postoperative vision of 6/18 or better. Four of 362 (1.1%) of ECCE group and six of 344 (1.7%) of MSICS group had corrected postoperative visual acuity less than 6/60. There were no significant differences between the two groups for intraoperative and severe postoperative complications.\n MSICS and ECCE are both safe and effective techniques for treatment of cataract patients in community eye care settings. MSICS needs similar equipment to ECCE, but gives better uncorrected vision.", "an effective method for cataract surgery should be identified to combat cataract blindness.\n to study the surgical outcome of conventional extracapsular cataract extraction versus manual small-incision cataract surgery.\n a randomized clinical trial was carried out including one hundred eyes (88 patients) which were divided into two groups using systematic randomization: groups of conventional extracapsular cataract extractionwith posterior chamber intraocular lens (ECCE with PCIOL) implantation and manual small-incision cataract surgery (MSICS). The postoperative parameters/variables studied were the unaided and best-corrected visual acuity and astigmatism.\n epi info 2000 version statistical software was used for data analysis and calculation of relative risk, 95% CI and p value. The p value of less than 0.05 was considered as significant.\n in the immediate postoperative period, unaided visual acuity of =or> 6/18 was achieved in 24 subjects in MSICS group versus 7 in ECCE with PCIOL group (RR=2.05, 95% CI= 1.44 - 2.94, p = 0.0002), whereas the same at 6 - 8 weeks postoperatively was found in 28 and 22 subjects in those groups respectively (RR=1l.27, 95% CI=0.86-1.89, p=0.23). The astigmatism of =or> 2 at6 - 8 weeks was found in 35 and 17 subjects from the conventional and MSICS groups respectively ( R=2.28, 95% CI= 1.39-3.73, p=0.0002).\n both MSICS and conventional ECCE with PCIOL are safe and effective techniques for treatment of cataract patients. A more rapid recovery of good vision can be achieved with MSICS than with conventional ECCE with PCIOL in the immediate postoperative period.", "To compare the surgically induced astigmatism (SIA) and endothelial cell loss following conventional extracapsular cataract surgery (ECCE), manual small-incision cataract surgery (Blumenthal technique)(SICS) and phacoemulsification (PE) with non-foldable intraocular lens implantation.\n 186 cataractous eyes with nuclear sclerosis grade 3 or less were randomized to undergo ECCE, SICS or PE with intraocular lens (non-foldable) implantation after a detailed pre-operative assessment. Keratometry and specular microscopy were performed pre-operatively and 6 weeks postoperatively. Surgically induced astigmatism was calculated using the rectangular coordinate method (Holladay et al.).\n Mean endothelial cell loss was similar for all three groups (p = 0.855); ECCE induced a loss of 4.72% (SD: 13.07); SICS 4.21% (SD: 10.29) and PE 5.41% (SD: 10.99). Mean SIA was 1.77D (1.61D) for the ECCE group, 1.17D (0.95D) for the SICS group and 0.77D (0.65D) for the PE group (p = 0.001). The magnitude of the difference between the SICS and the PE group was 0.4D.\n PE induced less astigmatism than SICS and ECCE in this study but the magnitude of the difference between SICS and PE was small. There was no significant difference in endothelial cell loss between the three groups." ]

[ "7501140", "19367356", "18790598", "14673053", "2972270", "7611638", "18809275", "10901342", "15232328", "10665616", "15824361", "14759641", "15679006", "1641137", "3902184", "11176767", "2730380", "15824337", "17869448", "2889518", "17687152", "16648508" ]

[ "Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.", "Modafinil effects in multiple sclerosis patients with fatigue.", "A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer.", "Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program.", "Amantadine, fatigue, and multiple sclerosis.", "A double-blind, placebo-controlled trial of amantadine for the treatment of fatigue in patients with the post-polio syndrome.", "L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study.", "Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial.", "Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial.", "A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms.", "A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis.", "Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial.", "Randomized trial of paroxetine in end-stage COPD.", "A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis.", "Amantadine therapy for fatigue in multiple sclerosis.", "A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease.", "Amantadine treatment of fatigue associated with multiple sclerosis.", "Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study.", "A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy.", "A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. The Canadian MS Research Group.", "Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial.", "Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial." ]

[ "To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue.\n Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known.\n Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response.\n Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo.\n Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.", "To investigate the effects of Modafinil on focused attention, motor function and motor excitability in patients with multiple sclerosis (MS) and fatigue.\n 21 MS patients with fatigue were enrolled in this double-blind placebo-controlled study. Modafinil (MOD) or placebo (PL) was administered for 8 weeks. The d2 alertness test, the Nine Hole Peg Test (9HPT) and several transcranial magnetic stimulation (TMS) techniques were applied prior to and after the first drug ingestion and well as after 8 weeks of drug intake.\n Prior to the first drug intake, the two groups were comparable. After the first drug ingestion, fatigue as measured by the Fatigue Severity Scale (FSS), performance of the d2 test and the 9HPT improved significantly in the MOD group and remained better than in the PL group after 8 weeks of treatment. Patients in the MOD group made fewer mistakes in the D2 test without being slower. They completed the 9HPT faster. Motor evoked potential amplitudes produced by paired pulse TMS were larger in the MOD group than the PL group. Motor thresholds and silent period durations remained unchanged.\n Compared to PL, MOD improved fatigue, focused attention and dexterity and enhanced motor cortex excitability in this group of patients. MOD may be helpful in MS patients with fatigue to improve cognitive and motor abilities.", "Fatigue is very common in patients with cancer. Current guidelines suggest that psychostimulants are \"reasonable to consider for severe fatigue.\" This randomized, double-blind, placebo-controlled trial investigated the hypothesis that dexamphetamine in fatigued patients with advanced cancer would produce a clinically significant improvement with minimal side effects. Fifty patients with advanced cancer, who were receiving palliative care, were randomized to dexamphetamine 10mg twice daily or placebo for eight days. Effectiveness was assessed using the Brief Fatigue Inventory and the McGill Quality-of-Life Questionnaire. The side effects were recorded. The results were analyzed on an intention-to-treat basis. The baseline demographics, fatigue levels, and quality-of-life scores were similar between the two arms. Patients were elderly, had impaired performance status (Eastern Cooperative Oncology Group score=3), and were taking a range of neurologically active medications. Thirty-nine patients completed the trial. There was a transient improvement in the fatigue levels on day 2, but no significant difference in fatigue (P=0.267) or quality of life (P=0.579) by the end of the study. Statistical modeling did not reveal any significant predictors of response to dexamphetamine. These results suggest that dexamphetamine 20mg daily, although well tolerated, does not significantly improve fatigue or quality of life in patients with advanced cancer, as measured by the selected instruments.", "Fatigue and depression typically occur together in cancer patients, suggesting a common etiology, perhaps based on serotonin. This randomized clinical trial tested whether paroxetine, a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue in cancer patients and whether any reduction was related to depression.\n Cancer patients undergoing chemotherapy for the first time were assessed for fatigue. Of 704 patients who reported fatigue at their second chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of fatigue and depression were performed at cycles 3 and 4 of chemotherapy.\n A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data. No difference was detected in fatigue between patient groups. At the end of the study, there was a difference between groups in the mean level of depression (Center for Epidemiologic Studies Depression scores, 12.0 v 14.8, respectively; P <.01).\n Paroxetine had no influence on fatigue in patients receiving chemotherapy. A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels.", "In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis, we found amantadine hydrochloride therapy to be effective in improving fatigability in six. Administration of the drug was associated with significantly higher levels of beta-endorphin-beta-lipotropin and responders had significantly higher levels than nonresponders. Lactate levels were significantly higher and pyruvate levels lower in nonresponders. Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation.", "Because amantadine has been shown to reduce fatigue in patients with multiple sclerosis, we performed a double-blind, placebo-controlled study to assess its efficacy in the disabling symptom of post-polio fatigue. Twenty-three patients completed six weeks of therapy. Fatigue was measured by the patients using visual analogue scales (twice per day) and numerical fatigue severity scales (once per week) and by overall impression (at end of therapy). Formal neuropsychological testing and serum drug levels were performed to assess compliance. On all measures, no significant difference was found between treatment and placebo groups. Fifty-four percent of patients given amantadine and 43% given placebo reported a decrease in fatigue; however, the visual analogue scales and fatigue severity scales failed to reflect any improvement. Several patients in the treatment group elected to continue amantadine therapy after the study was completed. Our findings suggest that amantadine is not significantly better than placebo in reducing the sensation of fatigue in post-polio syndrome, and that the measures we employed were insensitive to capture the subjective response experienced by a few patients.", "Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly improved FACT-An functional well-being subscale (P<0.03), and KPS (P<0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients.", "This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus (HIV). Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with medical illness and an uncertain, but limited, life expectancy.\n Primary inclusion criteria included the presence of a DSM-IV depressive disorder, debilitating fatigue, and no history of dependence on stimulants. The study consisted of a 2-week randomized, placebo-controlled trial, with the blind maintained until week 8 for responders, followed by open treatment through the completion of 6 months.\n Of 23 men who entered the study, 22 completed the 2-week trial. Intent-to-treat analysis indicated that 73% of patients (8/11) randomly assigned to dextroamphetamine reported significant improvement in mood and energy, compared with 25% (3/12) among placebo patients (Fisher exact test, p < .05). Both clinician- and self-administered measures indicated significantly improved mood, energy, and quality of life among patients taking dextroamphetamine. There was no evidence of the development of tolerance of, abuse of, or dependence on the medication.\n These results suggest that dextroamphetamine is a potentially effective, fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue.", "While testosterone's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature, no placebo-controlled trial selecting for depressive disorders and including a standard antidepressant has been conducted. Accordingly, this double-blind trial was designed to determine whether testosterone, as well as fluoxetine, is superior to placebo for depression, fatigue, or both.\n One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depressive disorder entered the 8-week trial and were randomized to testosterone (up to 400 mg IM testosterone cypionate biweekly), fluoxetine (up to 60 mg/d), or double placebo. Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue, the Hamilton Rating Scale for Depression, and the Chalder Fatigue Scale.\n Ninety men completed the trial. In intention-to-treat analyses, mood response rates were 54%, 47%, and 44% for fluoxetine, testosterone, and placebo, respectively. Among completers, mood response rates were 70%, 57%, and 53%, respectively; in neither analysis were differences between treatments statistically significant. In contrast, testosterone was superior to fluoxetine and placebo for completers regarding fatigue. In intention-to-treat analysis, response rates were 39%, 56%, and 42% for fluoxetine, testosterone, and placebo, respectively, and for study completers, 41%, 63%, and 52%, respectively, (P < 0.05),\n While over 50% of patients treated with testosterone reported improved mood, this rate was not statistically superior to placebo. Thus, our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men. However, if validated in additional studies, testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression.\n Copyright 2004 Lippincott Williams and Wilkins", "The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms (diminished libido, depressed mood, low energy, and depleted muscle mass) in men with symptomatic human immunodeficiency virus illness.\n Seventy-four patients were enrolled in a double-blind, placebo-controlled 6-week trial with bi-weekly testosterone injections, followed by 12 weeks of open-label maintenance treatment. Major outcome measures were Clinical Global Impressions Scale ratings for libido, mood, energy, and erectile function; Hamilton Depression Rating Scale scores, and Chalder Fatigue Scale scores. Body composition changes were assessed with bioelectric impedance analysis.\n Seventy men completed the 6-week trial. Response rates, defined as much or very much improved libido, were 74% (28/38) for patients randomized to testosterone, and 19% (6/32) for placebo-treated patients (P<.001). Of the 62 completers with fatigue at baseline, 59% (20/34) receiving testosterone and 25% (7/28) receiving placebo reported improved energy (P<.01). Among the 26 completers with an Axis I depressive disorder at baseline, 58% of the testosterone-treated patients reported improved mood compared with 14% of placebo-treated patients (Fisher exact test = .08). With testosterone treatment, average increase in muscle mass over 12 weeks was 1.6 kg for the whole group, and 2.2 kg for the 14 men with wasting at baseline. Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks.\n Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness, restoring libido and energy, alleviating depressed mood, and increasing muscle mass.", "Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.", "Treatment with acetyl L-carnitine (ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome, but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis (MS). To compare the efficacy of ALCAR with that of amantadine, one of the drugs most widely used to treat MS-related fatigue, 36 MS patients presenting fatigue were enrolled in a randomised, double-blind, crossover study. Patients were treated for 3 months with either amantadine (100 mg twice daily) or ALCAR (1 g twice daily). After a 3-month washout period, they crossed over to the alternative treatment for 3 months. Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale (FSS), the primary endpoint of the study. Secondary outcome variables were: Fatigue Impact Scale (FIS), Beck Depression Inventory (BDI) and Social Experience Checklist (SEC). Six patients withdrew from the study because of adverse reactions (five on amantadine and one on ALCAR). Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale (p = 0.039). There were no significant effects for any of the secondary outcome variables. The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue.", "Although the underlying pathology is initially confined to the lungs, the associated emotional responses to chronic obstructive pulmonary disease (COPD) contribute greatly to the resulting morbidity. The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms.\n We conducted a 12-week, randomized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Questionnaire (CRQ), an evaluative COPD-specific quality-of-life questionnaire, was the primary outcome.\n 23 patients were randomized and 15 completed the trial (8 on Paroxetine; 7 on placebo). In the per-protocol analysis, we observed statistically and clinically significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ: emotional function (adjusted mean difference: 1.1; 95% confidence interval [CI]: 0.0 - 2.2) and mastery (difference: 1.1; CI: 0.4 - 1.8). Dyspnea and fatigue improved, but to an extent that did not reach statistical significance. In the intention-to-treat analysis, none of the differences in CRQ scores was significant. Paroxetine was not associated to any worsening of respiratory symptoms.\n The results of this small randomized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present. This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD.", "Fatigue occurs in a majority of patients with MS and is generally independent of measurable neurologic disability. Few options for treatment are available. We conducted a double-blind, placebo-controlled, crossover trial for each of two 4-week treatment periods. Forty-six eligible patients entered and five dropped out due to concurrent exacerbations. Nineteen patients (46.3%) experienced excellent or good relief of fatigue with pemoline, and eight patients (19.5%) with placebo (p = 0.06, Fisher's exact test). One-fourth of patients did not tolerate the drug well, and 7% had to discontinue pemoline during the study due to side effects. The most common side effects were anorexia, irritability, and insomnia. Pemoline may be an effective short-term treatment for fatigue associated with MS, but its adverse effects are not well tolerated by many patients.", "We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5% unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects.", "Fatigue is a commonly encountered symptom of human immunodeficiency virus (HIV) disease, associated with significant psychological and functional morbidity and poor quality of life. Preliminary studies on the treatment of fatigue from the cancer and multiple sclerosis literature suggest that psychostimulants may be effective in reducing fatigue.\n To compare the efficacy of 2 psychostimulant medications, methylphenidate hydrochloride (Ritalin) and pemoline (Cylert), with a placebo intervention for the treatment of fatigue in patients with HIV disease.\n In this double-blind trial, 144 ambulatory patients with HIV disease and persistent and severe fatigue were randomized to treatment with methylphenidate, pemoline, or placebo. Medications were titrated up to a maximum dose of 60 mg of methlyphenidate hydrochloride, 150 mg of pemoline, or 8 capsules of placebo daily. Fatigue was measured using 2 self-reported rating scales, the Piper Fatigue Scale (PFS) and the Visual Analogue Scale for Fatigue (VAS-F). We also used the timed isometric unilateral straight leg-raising task, a measure of muscular endurance. Quality-of-life and psychological well-being measures included the Beck Depression Inventory, the Brief Symptom Inventory, and the 36-Item Short-Form Medical Outcomes Study Health Status Survey. Side effects were monitored using the Systematic Assessment for Treatment Emergent Events and the Extra-pyramidal Symptom Rating Scale. All measures were rated weekly.\n One hundred nine subjects completed the 6-week trial; 15 patients (41%) receiving methylphenidate and 12 patients (36%) receiving pemoline demonstrated clinically significant improvement compared with 6 patients (15%) receiving placebo. Patients receiving methylphenidate or pemoline demonstrated significantly more improvement in fatigue on several self-reported rating scales (PFS total score, P=.04; affective subscale, P=.008; sensory subscale, P=.04; and VAS-F energy subscale, P=.02). Analysis of the regression slopes by means of hierarchical linear modeling demonstrated a significantly greater rate of improvement in PFS total scores among patients receiving psychostimulants compared with the placebo group (P=.02). There were no significant differences in the efficacy between methlyphenidate and pemoline on any outcome measure studied. Improvement in fatigue was also significantly correlated with improvement in measures of depression, psychological distress, and overall quality of life. Severe side effects were relatively uncommon among this sample, and only hyperactivity or jitteriness occurred significantly more often among subjects receiving active medication.\n Many patients with HIV- and acquired immunodeficiency syndrome-unrelated fatigue respond favorably to treatment with methylphenidate or pemoline. Both psychostimulants appear to be equally effective and significantly superior to placebo in decreasing fatigue severity with minimal side effects. Moreover, improvement of fatigue was significantly associated with improved quality of life and decreased levels of depression and psychological distress.", "Fatigue is a common symptom of multiple sclerosis (MS) that is without an effective treatment. A double-blind, controlled study of fatigue treatment was conducted to evaluate the efficacy of amantadine hydrochloride in treating MS-associated fatigue. Since fatigue cannot be characterized by a single symptom or behavior, a variety of neuropsychological, behavioral, and self-report measures were used to monitor changes across different systems. According to patients' daily diary ratings, amantadine produced small but statistically significant improvements in fatigue across four of seven dimensions (overall energy level, concentration, problem solving, and sense of well-being). In addition, patients with MS who were taking amantadine performed slightly better on the Stroop Interference Test, an attentional measure of freedom from distracting information. Although retrospective reports by patients with MS did not confirm the degree of improvement recorded on a daily basis, the study's results suggested that amantadine may offer modest benefits in alleviating the day-to-day subjective experience of fatigue.", "To assess whether modafinil, a wakefulness-promoting agent, is useful for fatigue in patients with multiple sclerosis (MS).\n Patients with MS with stable disability, and a baseline score of 45 or more on the Modified Fatigue Impact Scale (MFIS), were eligible for the 5-week randomized, double-blind, placebo-controlled, parallel group study. The initial daily dose of modafinil was 200 mg for 1 week. Depending on tolerance, the dose was increased by 100 mg every week up to 400 mg/day and remained unchanged between day 21 and day 35. The primary outcome variable was the change of MFIS score at day 35.\n A total of 115 patients with MS were enrolled in the study and in the intention to treat analysis. The mean MFIS score at baseline was 63 +/- 9 in the placebo group and 63 +/- 10 in the modafinil group. MFIS scores improved between day 0 and day 35 in both placebo-treated and modafinil-treated groups, but no significant difference was detected between the two groups. There was no major safety concern.\n There was no improvement of fatigue in patients with multiple sclerosis treated with modafinil vs placebo according to the Modified Fatigue Impact Scale.", "The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT.\n Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam.\n The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms.\n Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL.", "One hundred and fifteen patients with definite multiple sclerosis (M.S.) and chronic persistent fatigue were studied. This ten-week cross-over study consisted of a 2-week baseline period and two 3-week treatment periods separated by a 2-week washout. Patients received either amantadine 100 mg bid or matching placebo capsules. Fatigue, the effect of fatigue on an individually pre-selected activity and its effect on activities of daily living, were evaluated. Amantadine produced a small but statistically significant decrease in fatigue. An important placebo effect was noted. Mean fatigue during the washout period was lower than during the placebo run-in period, independently of which treatment had been given first. Side effects were numerous both on amantadine and on placebo. Only insomnia was significantly more common with amantadine.", "To evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F).\n Patients with fatigue score >or= 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) for more than 1 week were included. Patients were randomly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days. A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level. All patients were offered open-label donepezil during the second week. FACIT-F and/or the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 11, and 15. The FACIT-F fatigue subscale score on day 8 was considered the primary end point.\n Of 142 patients randomly assigned to treatment, 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis. Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .57) or ESAS (P = .18) between groups. In the open-label phase, fatigue intensity continued to be low as compared with baseline. No significant toxicities were observed.\n Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue.", "To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F).\n Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point.\n Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed.\n Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention." ]

[ "8375791", "3542766", "8974970", "12040357", "23195811", "7019949" ]

[ "[Crataegus Special Extract WS 1442 in NYHA II heart failure. A placebo controlled randomized double-blind study].", "[Treatment of decreasing cardiac performance. Therapy using standardized crataegus extract in advanced age].", "[Crataegus Special Extract WS 1442. Assessment of objective effectiveness in patients with heart failure (NYHA II)].", "Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure.", "Efficacy of the Hawthorn (Crataegus) preparation LI 132 in 78 patients with chronic congestive heart failure defined as NYHA functional class II.", "[The clinical effect of Crataegutt in heart disease of ischemic or hypertensive origin. A multicenter double-blind study]." ]

[ "In 30 patients with stage NYHA II cardiac insufficiency, a placebo-controlled randomized double-blind study was carried out to determine the efficacy of the Crataegus special extract WS 1442. Treatment duration was 8 weeks, and the substance was administered at a dose of 1 capsule taken twice a day. The main target parameters were alteration in the pressure-x-rate product (PRP) under standardised loading on a bicycle ergometer, and a score of subjective improvement of complaints elicited by a questionnaire. Secondary parameters were exercise tolerance and the change in heart rate and arterial blood pressure. The active substance group showed a statistically significant advantage over placebo in terms of changes in PRP (at a load of 50 W) and the score, but also in the secondary parameter heart rate. In both groups, systolic and diastolic blood pressure was mildly reduced. No adverse reactions occurred.", "nan", "In a multicenter, placebo-controlled double-blind study, the efficacy of the Crataegus-Specialextrakt WS 1442 in patients with NYHA stage II cardiac insufficiency was investigated. A total of 136 patients with this diagnosis were admitted to the study and, following a 2-week run-in phase, treated with Crataegus-Specialextract or placebo over a period of 8 weeks. The primary target parameter was the change in the difference of the pressure, heart rate product (systolic blood pressure x heart rate/100) (PHRP 50 W load vs. rest) measured at the beginning and end of treatment.\n On the basis of this variable, a clear improvement in the performance of the heart was shown in the group receiving the test substance, while the condition of the placebo group progressively worsened. The therapeutic difference between the groups was statistically significant. The positive result for the objective efficacy parameter was confirmed by a statistically obvious superiority of Crataegus in the patient's own assessment of improvement in the main symptoms (reduced performance, shortness of breath, ankle edema etc.). In addition, active treatment led, in comparison with placebo, to a considerably better quality of life for the patient, in particular with respect to mental well-being. The tolerability of the active substance proved to be very good-as shown by comprehensive laboratory investigations and the recording of undesirable events.\n All in all, the results of the present clinical investigation confirm those of previous studies showing that Crataegus-Specialextrakt WS 1442 is an effective and low-risk phytotherapeutic form of treatment in patients with NYHA II cardiac insufficiency.", "The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated.\n Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed. Efficacy and tolerability of the treatments were judged by both the patients and investigators. Safety was assessed by the documentation of adverse events and the safety laboratory.\n A total of 209 patients were randomized to treatment with 1800 mg of WS 1442, 900 mg of WS 1442, or with placebo. After 16 weeks of therapy with 1800 mg of WS 1442 per day, maximal tolerated workload during bicycle exercise showed a statistically significant increase in comparison with both placebo and 900 mg of WS 1442. Typical heart failure symptoms as rated by the patients were reduced to a greater extent by WS 1442 than by placebo. This difference was significant for both doses of WS 1442. Both efficacy and tolerability were rated best for the 1800 mg of WS 1442 group by patients and investigators alike. The incidence of adverse events was lowest in the 1800 mg of WS 1442 group, particularly with respect to dizziness and vertigo.\n The data from this study confirm that there is a dose-dependent effect of WS 1442 on the exercise capacity of patients with heart failure and on typical heart failure-related clinical signs and symptoms. The drug was shown to be well tolerated and safe.", "Seventy-eight male and female patients between the ages of 45 and 73, who were affected by chronic heart failure defined as NYHA functional class II, were treated either with Crataegus extract or with a placebo preparation. The extract LI 132 was administered to the patients in the form of 3 dragées a day (verum preparation) corresponding to a daily dose of 600 mg. Treatment was continued over a period of 8 weeks, with a wash-out phase of one week. The confirmatory parameter used to asses the efficacy of the preparation was the patients' working capacity which was measured using an ergometer bicycle. Before the start of the study, an increase in the patients' working capacity of at least half an exercise step on the ergometer bicycle (12.5 watt) was determined to be clinically relevant. Apart from the compatibility of the preparation, a score system was used to assess the severity level of the typical symptoms. From day 0 to day 56 of the trial, the median values obtained for the working capacity of the patients treated with the verum preparation were found to have increased by 28 watt, while the increase in the working capacity of the placebo patients was as little as 5 watt. The difference was statistically significant (p < 0.001). Apart from that, a significant reduction of the systolic blood pressure, of the heart rate and of the pressure/rate product was observed for the patients treated with the verum preparation, compared to the patients treated with the placebo preparation. Also, the clinical symptoms (score system) were found to have improved significantly. There were no severe side effects observed.\n Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.", "nan" ]

[ "15627538", "4735291", "15321086", "10655924", "14980943", "15636811", "15264729", "8644400", "8192733", "11914565", "7999486", "15321608", "7747861", "11843734", "11915786", "8092223", "8494130", "7574020", "10566921", "7577275", "11025238", "15321106", "11573527", "2265052", "14517641", "15321547", "1642918", "9349079", "12075638", "19471789", "15321345", "14570793", "12693997", "15321241", "10410403", "14633562", "9597213", "9168215", "10365009", "15321623", "10930199", "15918823", "16095463", "8779366", "10598596", "15636905", "11952447", "11843736", "10648315", "9024025" ]

[ "Hemodynamic effects of spinal anesthesia and simultaneous intravenous bolus of combined phenylephrine and ephedrine versus ephedrine for cesarean delivery.", "The use of inflatable boots to prevent hypotension during spinal anesthesia for cesarean section.", "The effect of prophylactic glycopyrrolate on maternal haemodynamics following spinal anaesthesia for elective caesarean section.", "Comparison of pentastarch and Hartmann's solution for volume preloading in spinal anaesthesia for elective caesarean section.", "Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery.", "Ephedrine and phenylephrine for avoiding maternal hypotension due to spinal anaesthesia for caesarean section. Effects on uteroplacental and fetal haemodynamics.", "Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section.", "[Compression stockings as prevention of hypotension in Cesarean section during spinal anesthesia].", "A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section.", "Influence of volume preloading on uteroplacental and fetal circulation during spinal anaesthesia for caesarean section in uncomplicated singleton pregnancies.", "Spinal anaesthesia for caesarean section: comparison of infusions of phenylephrine and ephedrine.", "Effect of lateral versus supine wedged position on development of spinal blockade and hypotension.", "Maternal position during induction of spinal anaesthesia for caesarean section. A comparison of right lateral and sitting positions.", "Glycopyrronium and hypotension following combined spinal-epidural anaesthesia for elective Caesarean section in women with relative bradycardia.", "Prophylactic intravenous bolus ephedrine for elective Caesarean section under spinal anaesthesia.", "Comparison of prophylactic angiotensin II versus ephedrine infusion for prevention of maternal hypotension during spinal anesthesia.", "Leg elevation and wrapping in the prevention of hypotension following spinal anaesthesia for elective caesarean section.", "Prevention of hypotension after spinal anesthesia for cesarean section: six percent hetastarch versus lactated Ringer's solution.", "Preoperative dextrose does not affect spinal-induced hypotension in elective Cesarean section.", "Effect of crystalloid and colloid preloading on uteroplacental and maternal haemodynamic state during spinal anaesthesia for caesarean section.", "Hemodynamic effects of simultaneous administration of intravenous ephedrine and spinal anesthesia for cesarean delivery.", "Warm or cold saline for volume preload before spinal anaesthesia for caesarean section?", "Evaluation of pre-emptive intramuscular phenylephrine and ephedrine for reduction of spinal anaesthesia-induced hypotension during Caesarean section.", "Prevention of hypotension following spinal anaesthesia for elective caesarean section by wrapping of the legs.", "Comparative effect of 6% hydroxyethyl starch (containing 1% dextrose) and lactated Ringer's solution for cesarean section under spinal anesthesia.", "Combined spinal epidural anaesthesia for caesarean section: a randomised comparison of Oxford, lateral and sitting positions.", "Rapid administration of crystalloid preload does not decrease the incidence of hypotension after spinal anaesthesia for elective caesarean section.", "Prevention of hypotension during spinal anaesthesia for caesarean section: ephedrine infusion versus fluid preload.", "Effectiveness of intravenous ephedrine infusion during spinal anaesthesia for caesarean section based on maternal hypotension, neonatal acid-base status and lactate levels.", "[Preload during spinal anesthesia for cesarean section: comparison between crystalloid and colloid solutions.].", "Thromboembolic deterrent stockings fail to prevent hypotension associated with spinal anaesthesia for elective caesarean section.", "Sequential compression device with thigh-high sleeves supports mean arterial pressure during Caesarean section under spinal anaesthesia.", "Hypotension following combined spinal-epidural anaesthesia for Caesarean section. Left lateral position vs. tilted supine position.", "Prophylactic ephedrine and hypotension associated with spinal anesthesia for cesarean delivery.", "Prevention of hypotension after spinal anesthesia for cesarean section: dextran 40 versus lactated Ringer's solution.", "The effect of right versus left lateral decubitus positions on induction of spinal anesthesia for cesarean delivery.", "Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated with spinal anaesthesia for Caesarean section.", "The effect of head-down tilt position on arterial blood pressure after spinal anesthesia for cesarean delivery.", "Glycopyrrolate reduces nausea during spinal anaesthesia for caesarean section without affecting neonatal outcome.", "The use of thromboembolic deterrent stockings and a sequential compression device to prevent spinal hypotension during caesarean section.", "Hydroxyethylstarch 10% is superior to Ringer's solution for preloading before spinal anesthesia for Cesarean section.", "A comparison of the lateral, Oxford and sitting positions for performing combined spinal-epidural anaesthesia for elective Caesarean section.", "Colloid vs. crystalloid preloading to prevent maternal hypotension during spinal anesthesia for elective cesarean section.", "Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia.", "Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section.", "Prevention of hypotension during spinal anaesthesia for caesarean section.", "Effect of delayed supine positioning after induction of spinal anaesthesia for caesarean section.", "Maternal cardiovascular consequences of positioning after spinal anaesthesia for Caesarean section: left 15 degree table tilt vs. left lateral.", "Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal anesthesia in prehydrated cesarean delivery patients.", "Acupressure versus intravenous metoclopramide to prevent nausea and vomiting during spinal anesthesia for cesarean section." ]

[ "Hypotension following spinal anesthesia for cesarean delivery can produce adverse maternal symptoms and neonatal acid-base effects. Single-agent prophylaxis, most notably with ephedrine, does not reliably prevent spinal anesthesia-induced hypotension; recently, however, the prophylactic use of phenylephrine with ephedrine as an infusion was observed to be effective. We postulated that this combination, when given as an intravenous bolus for prophylaxis and rescue treatment, could be similarly effective.\n Forty-three term parturients were randomized to receive a bolus of ephedrine 10 mg +/- phenylephrine 40 microg (groups E and EP, respectively) simultaneously with spinal anesthesia. Hypotension was defined as a systolic blood pressure below 100 mmHg or a decrease of 20% from a baseline value. Rescue boluses comprised of ephedrine 5 mg +/- phenylephrine 20 microg.\n For groups E and EP, respectively, the incidence of hypotension was 80% vs. 95% (P=0.339), with the mean number of rescue boluses being 3.85+/-3.7 and 3.05+/-1.7 and the mean umbilical artery pH being 7.246+/-0.081 vs. 7.244+/-0.106. All comparisons were not significant (NS).\n The combination of ephedrine and phenylephrine given as an intravenous bolus at the doses selected is not superior to ephedrine alone in preventing or treating hypotension in healthy parturients undergoing cesarean delivery.", "nan", "We conducted a randomised controlled trial to compare the severity of hypotension and ephedrine requirements following spinal anaesthesia for elective caesarean section in women pretreated with either i.v. glycopyrrolate 4.0 microg/kg (group G) or saline (group S). Data were analysed using sequential analysis which allowed us to terminate the study after data from 40 patients had been analysed (20 in each group). There were no differences between the two groups in the severity of hypotension (mean +/- SD decrease from baseline 35 +/- 14% in group G and 29 +/- 15% in group S) or ephedrine requirements (15 +/- 11 mg in group G and 18 +/- 12 mg in group S). Intra-operative heart rate increased by a greater amount in group G than in group S (58 +/- 26% vs 35 +/- 21% mean +/- SD;P = 0.002) and there was a greater incidence of dry mouth (75% vs 15%;P = 0.0006) but no difference in the incidence of nausea and vomiting (30% vs 50%;P = 0.33). Pretreatment with glycopyrrolate did not confer an advantage in this study.", "We studied 160 patients undergoing elective Caesarean section under spinal anaesthesia who received a preloading volume of 15 ml kg-1 of 10% pentastarch in 0.9% saline, or Hartmann's solution, in a prospective, randomized, double-blind study. We compared the incidence of spinal-induced hypotension in each group. Hypotension was defined as a decrease in systolic arterial pressure to less than 70% of baseline values or < or = 90 mm Hg, whichever was the greater. The groups were comparable in physical characteristics and there was no serious morbidity. Fetal outcome was similar in both groups. Significantly more patients in the Hartmann's group (n = 38, 47.5%) developed hypotension than in the pentastarch group (n = 10, 12.5%) (P < 0.0001). Linear regression analysis showed that the only significant variable was type of fluid used. Blood glucose concentrations were not related to the presence of hypotension. We conclude that starches may be suitable for preloading in Caesarean section under spinal anaesthesia and provide an alternative to the aggressive use of vasoconstrictors.", "In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery.\n In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine.", "The effects of i.v. vasopressors on Doppler velocimetry of the maternal uterine and placental arcuate arteries and the fetal umbilical, renal and middle cerebral arteries were studied during spinal anaesthesia in 19 healthy parturients undergoing elective caesarean section. Fetal myocardial function was investigated at the same time by M-mode echocardiography. The patients were randomized into two groups, to be given either ephedrine or phenylephrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure decreased by more than 10 mmHg from the control value. Both the vasopressors restored maternal arterial pressure effectively. The ephedrine group showed no significant differences in any of the Doppler velocimetry recordings relative to the baseline values, but during the phenylephrine infusion the blood flow velocity waveform indices for the uterine and placental arcuate arteries increased significantly and vascular resistance decreased significantly in the fetal renal arteries. Healthy fetuses seem to tolerate these changes in uteroplacental circulation well, however, since the Apgar scores for the newborns and the acid-base values in the umbilical cord were within the normal range in both groups. The results suggest that some caution is required when selecting the specific vasopressor agent, the dosage and the mode of administration for the treatment of maternal hypotension secondary to spinal anaesthesia for caesarean section.", "Current methods of crystalloid preload administration prior to spinal anaesthesia for elective caesarean section are relatively ineffective in preventing hypotension. This study examined the relevance of the timing of the fluid administered. Fifty women were randomly allocated to receive either 20 ml x kg(-1) of crystalloid solution during 20 minutes prior to induction of spinal anaesthesia (preload), or an equivalent volume by rapid infusion immediately after induction (coload). Significantly more patients in the coload group did not require vasopressor therapy pre-delivery (P=0.047). The coload group required a lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses for the treatment of maternal hypotension pre-delivery. There was no between-group difference in either the total cumulative dose, or in the total number of doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid crystalloid administration after, rather than over 20 minutes before the induction of spinal anaesthesia for elective caesarean section, may be advantageous in terms of managing maternal blood pressure prior to delivery.", "Inflatable splints and wrapping of the legs have been shown to be effective against hypotension during spinal anaesthesia for Caesarean section. The aim of this study was to investigate if compression stockings could have a similar effect. Thirty healthy mothers scheduled for elective Caesarean section were randomised to have either compression stockings or no stockings on before spinal anaesthesia. The stockings had a pressure effect of 54 mmHg. The women were preloaded with 20 ml isotonic NaCl one hour preoperatively. Hypotension was defined as either a decrease in systolic blood pressure to 80% of preoperative values or systolic blood pressure under 100 mmHg. Blood pressure was measured every second minute, and ephedrine 5 mg was given in the presence of hypotension. Two patients were excluded in the control group. There were no differences in demographic data, extension of blockade, and spinal injection to delivery time. Nine patients in the group with stockings had either no fall in blood pressure or a fall in blood pressure corrected with only 5 mg ephedrine. In the control group the corresponding number was four patients (p < 0.12). Ephedrine dose between zero and 20 minutes and total ephedrine dose was significantly lower in the group with stockings than in the control group (p < 0.038). Five patients in the control group experienced nausea, no patients in the study group had nausea (p < 0.013). In conclusion, compression stockings stabilised the blood pressure during Caesarean section in spinal anaesthesia and led to a significant smaller need for ephedrine.", "Hypotension after spinal anesthesia for cesarean section remains a common and serious complication despite the use of uterine displacement and volume preloading. The current study revaluated the role of crystalloid volume preloading in this context.\n In a two-stage open sequential design, patients presenting for elective repeat cesarean section were allocated to receive either no preload or 20 ml/kg crystalloid administered over 15-20 min before spinal anesthesia. Hypotension was defined as a decrease in systolic pressure to less than 100 mmHg and to less than 80% of baseline value, and the study was designed to detect a 20% difference in the incidence of hypotension between the groups, with statistical significance at the 10% (alpha = 0.1) level, one-tailed.\n One hundred forty patients were studied. Hypotension occurred in 43 (55%, 95% CI 43.4-66.4) preloaded and 44 (71%, 95% CI 58-81.8) unpreloaded subjects, a difference in incidence of 16% (95% CI 0.04-31.6), which was statistically significant. There were no significant differences in the severity, timing, or duration of hypotension; the dose requirement for ephedrine; or the clinical and biochemical status of neonates between the groups. The only difference seen was a lower mean base excess (-3.4, SD 2.81 mM-1) in the neonates of hypotensive mothers compared to neonates of nonhypotensive mothers (-2.4, SD 1.99 mM-1).\n The study confirms that hypotension associated with spinal anesthesia for cesarean section cannot be eliminated by volume preloading in the supine wedged patient. The relatively small reduction in incidence of hypotension challenges our perception of the value of crystalloid preload. Though volume preload in the elective cesarean section is advocated, the requirement for a mandatory administration of a fixed volume before spinal anesthesia for urgent cases has been abandoned.", "Effects of volume preloading during spinal anaesthesia for elective caesarean section on maternal blood pressure, feto-maternal circulation and fetal outcome.\n In a pilot study a randomised trial was performed in 22 healthy women with uncomplicated, singleton pregnancies at 36-40 weeks of gestation undergoing elective caesarean section under spinal anaesthesia. In the low volume group (group A) patients received 150 ml of crystalloid solution for preloading, in the high volume group (group B) they were given 15 ml/kg of crystalloid solution for preloading before the initiation of spinal anaesthesia. Maternal blood pressure was monitored intermittently. Hypotension was defined as a decrease in systolic pressure to less than 80% of the baseline value. The Doppler flow evaluation consisted of measurements from the uterine artery at the placental site, fetal umbilical artery and fetal middle cerebral artery. Pulsatility indices were derived before and after fluid preloading, and when spinal anaesthesia was established. The neonatal outcome was assessed by Apgar scores, arterial acid base status and neurologic and adaptive capacity scores (NACS).\n The incidence of maternal hypotension in both groups was 45.5% (n = 10); 3 cases occurred in group A compared to 7 cases in group B (n.s.). There was no evidence that the high dose volume is useful in preventing maternal hypotension. The pulsatility indices of uterine arteries, umbilical arteries and middle cerebral arteries were not altered. Statistical analysis showed no changes in neonatal outcome concerning umbilical arterial pH, Apgar score and NACS (n.s.) between groups A and B.\n Our preliminary results suggest that high dose crystalloid volume preloading has no preventive function in the avoidance of maternal hypotension in healthy parturients undergoing elective caesarean section under spinal anaesthesia, and shows no harmful effects on neonatal outcome as long as maternal hypotension is corrected immediately. However, the statistical significance may reflect the small sample size, and larger series are needed before changing the current management.\n Copyright 2002 S. Karger AG, Basel", "Maternal cardiovascular changes and neonatal acid-base status were assessed in 29 healthy women undergoing elective lower segment Caesarean section under spinal anaesthesia. The patients were allocated randomly to one of three groups to receive an i.v. infusion of one of the following: ephedrine 1 mg min-1 (group E1: n = 10), ephedrine 2 mg min-1 (group E2: n = 9), or phenylephrine 10 micrograms min-1 (group P: n = 10). Invasive arterial pressure was monitored continuously and if hypotension occurred (defined as a 20% decrease from baseline, taken after i.v. preload administration), bolus doses of either ephedrine (6 mg in groups E1 and E2) or phenylephrine (20 micrograms in group P) were given. Only four patients became hypotensive in group E2, compared with eight patients in group E1 and nine patients in group P. The total time that the patients remained hypotensive was greatest in group P (P < 0.005), less in group E1 and least in group E2. Neonatal Apgar scores and acid-base profiles were similar in all three groups. In this study, an infusion of phenylephrine 10 micrograms min-1 with bolus doses of 20 micrograms was shown to be significantly less effective in maintaining systolic arterial pressure within 20% limits of baseline compared with an infusion of ephedrine 1 or 2 mg min-1 with bolus doses of 6 mg.", "Aortocaval compression may not be completely prevented by the supine wedged or tilted positions. It is commonly believed, however, that the unmodified full lateral position after induction of spinal anaesthesia might allow excessive spread of the block. We therefore compared baseline arterial pressures in the supine wedged, sitting, tilted and full lateral positions in 40 women who were about to undergo elective caesarean section. They were then given spinal anaesthesia in the left lateral position and randomised to be turned to the right lateral or the supine wedged position, after which speed of onset and spread of blockade to cold sensation were measured every 2 min for 10 min and mean arterial pressure and ephedrine requirement were recorded every minute for 20 min. Baseline mean arterial pressure was 9 mmHg (95% CI 3 to 14) lower in the left lateral (measured in the upper arm) than in the sitting position; those in the supine wedged and tilted positions were intermediate. Following spinal anaesthesia, hypotension (defined as a reading </=80% of the baseline value in the same position) lasted 2.4 min longer (CI +0.6 to +4.1) in the supine wedged group, but there was no significant difference between the groups in maximum fall or ephedrine requirement. The upper level of block rose more rapidly in the supine wedged than in the lateral group and showed less variability. There is therefore no reason to fear the unmodified lateral group position, which may offer better protection against hypotension.", "Forty women presenting for elective Caesarean section under spinal anaesthesia were randomly assigned to have anaesthesia induced in either the sitting or right lateral positions; 2.5 ml 0.5% hyperbaric bupivacaine was injected over 10 s before the mother was placed in a supine position with a 20 degree lateral tilt. The onset time and height of the subsequent analgesic and anaesthetic block was measured. It took longer to site spinal needles in the lateral position (240 vs 115 s, p < 0.001). There was a faster onset of sensory block to the sixth thoracic dermatomal level (8 vs 10 min, p < 0.001), in the lateral group, although onset time to T4 was comparable. There was no difference in maximum block height or degree of motor block. Mothers in the lateral group required more ephedrine in the first 10 m after siting the spinal (13.5 vs 10.5 mg, p < 0.05).", "The ability of glycopyrronium to reduce the severity of hypotension following subarachnoid block in parturients with a relative bradycardia was evaluated in a double-blind randomised controlled study. Women with a resting heart rate of < or = 80 beat x min(-1) presenting for elective Caesarean section were randomly allocated to receive either glycopyrronium 2 microg x kg(-1) or normal saline intravenously once positioned for combined spinal-epidural anaesthesia. Following spinal injection of 2.6 ml hyperbaric bupivacaine 0.5% and fentanyl 15 microg, women randomly allocated to the saline group were given 6 mg ephedrine so that all parturients received some prophylaxis against hypotension other than the fluid preload. Further ephedrine and fluid boluses were administered if mean arterial pressure fell 20% or more from resting values. Using a sequential analysis technique, analysis after the first 20 subjects indicated the study should be stopped, with no difference in ephedrine requirements or hypotension between the groups. We conclude that pretreatment with glycopyrronium 2 microg x kg(-1) is no more effective than 6 mg ephedrine in preventing hypotension following subarachnoid block in parturients with relatively low resting heart rates.", "To evaluate the efficacy and optimal dose of prophylactic intravenous ephedrine for the prevention of maternal hypotension associated with spinal anaesthesia for Caesarean section.\n After patients had received an intravenous preload of 0.5 L of lactated Ringer's solution, spinal anaesthesia was administered in the sitting position with hyperbaric bupivacaine 2.5 mL 0.5% combined with 25 microg fentanyl. A total of 68 patients were randomized to receive a simultaneous 2 mL bolus intravenously of either 0.9% saline (Group C, n = 20), ephedrine 6 mg (Group E-6, n = 24), or ephedrine 12 mg (Group E-12, n = 22). Further rescue boluses of ephedrine 6 mg were given if systolic arterial pressure fell to below 90 mmHg, greater than 30% below baseline, or if symptoms suggestive of hypotension were reported.\n There was a significantly higher incidence of hypotension in Group C (60% patients) compared to Group E-12 (27%), but not in Group E-6 (50%). The 95% Confidence Interval for the difference in proportions between Groups C and E-12 was 6-60%, P < 0.05. Fewer rescue boluses of ephedrine were required in Group E-12 compared with Group C (1.8 +/- 1.2 vs. 3.3 +/- 2.1, P < 0.05). There were no significant differences in the incidence of maternal nausea or vomiting, or of neonatal acidaemia between groups.\n A prophylactic bolus of ephedrine 12 mg intravenously given at the time of intrathecal block, plus rescue boluses, leads to a lower incidence of hypotension following spinal anaesthesia for elective Caesarean section compared to intravenous rescue boluses alone.", "Our purpose was to study the efficacy of ephedrine versus angiotensin II prophylactic infusions to counter maternal hypotension that occurs during spinal anesthesia at cesarean delivery.\n Healthy pregnant women undergoing elective repeat cesarean delivery at term with spinal anesthesia were randomized either to a control group (n = 10) or to one of two prophylactic infusion groups: angiotensin II (n = 10) or ephedrine (n = 10). Prophylactic infusions were titrated to a maternal diastolic blood pressure 0 to 10 mm Hg above baseline. Maternal and fetal blood samples for angiotensin II levels and acid-base status were obtained. Student's t test, chi 2, and analysis of variance were used.\n Mean arterial pressures were maintained after spinal anesthesia in the ephedrine and angiotensin II groups but decreased (p < 0.05) in the control group. Maternal angiotensin II levels rose with angiotensin II infusions but were unaltered in the other groups. Umbilical artery and vein angiotensin II levels were unaltered by angiotensin II infusions. Mean umbilical artery blood pH was lower (p < 0.05) in the ephedrine group than in the angiotensin II and control groups.\n In the healthy term fetus there is an advantage in using angiotensin II to maintain maternal blood pressure during regional anesthesia.", "Ninety-seven parturients undergoing elective Caesarean section were allocated randomly to have their legs elevated to approximately 30 degrees on pillows or elevated and wrapped with elasticated Esmarch bandages or neither (controls) following spinal anaesthesia. All patients received intravenous crystalloid (20 ml.kg-1 over 20 min) prior to spinal injection and were placed in the left lateral tilt position. Significant hypotension was treated with intravenous ephedrine in 5 mg bolus doses. Leg wrapping resulted in a significant reduction in the incidence of postspinal hypotension in comparison to the control group (18% compared to 53%, p = 0.004). This represents a five-fold reduction in the likelihood of postspinal hypotension (odds ratio 5.3, 95% CI 1.7-16.3). Leg elevation alone did not significantly reduce the incidence of hypotension (39%). There was no significant difference in the time of onset of hypotension between the groups. For those patients requiring ephedrine, there was no significant difference in mean dose requirements between the groups. The use of leg compression immediately postspinal provides a simple means of reducing the accompanying hypotension and should be used more widely.", "This study was designed to determine whether preoperative administration of 6% hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean section. Forty nonlaboring ASA class I and II women having nonurgent cesarean sections were randomized to receive either 500 mL of 6% hetastarch plus 1 L lactated Ringer's solution (LR) (n = 20), or 2 L of LR (n = 20) prior to induction of spinal anesthesia. Hypotension occurred in 45% of patients who received hetastarch vs 85% of those who received only LR (P < 0.05), and minimum systolic blood pressure was lower in the LR group than in the hetastarch group (85 +/- 12 vs 93 +/- 12 mm Hg [mean +/- SD]; P < 0.05). In addition, the LR group had a higher maximum heart rate (115 +/- 17 vs 104 +/- 16 bpm), a shorter mean time to hypotension (7 +/- 4 vs 10 +/- 7 min), and required more 5-mg doses of ephedrine for treatment of hypotension (0 vs 2 [median]; P < 0.05) than the hetastarch group. Neonatal outcome, as determined by Apgar scores and cord blood gas analyses, was good and similar in both groups. We conclude that 6% hetastarch plus LR is more effective than LR alone and that its routine use before spinal anesthesia for cesarean section should be considered.", "To determine if preoperative intravenous dextrose affects the incidence and ease of treatment of spinal-induced hypotension in parturients having elective Cesarean section under spinal anesthesia.\n In this prospective, double-blind study, following informed consent, 119 ASA I, II parturients for elective Cesarean section were randomized to receive intravenously either dextrose 5% in normal saline (Group D) or normal saline (Group NS) at 125 ml x hr(-1) for two hours prior to delivery. Following a bolus of 15 ml x kg(-1) normal saline iv, spinal anesthesia was induced with hyperbaric bupivacaine 0.75%, fentanyl and morphine. Hypotension (systolic blood pressure <100 mm Hg or >20% decrease) was treated with fluids and/or vasopressor. Data collected: demographics, blood glucose concentrations (fasting, time of spinal, delivery), blood pressure (baseline, one minute intervals from spinal to delivery), neonatal Apgar scores, umbilical blood gas analyses, glucose and lactate concentrations.\n There was no difference between the two groups in the rate of hypotension (P = 0.272). All parturients who experienced hypotension received fluids, and there was also no difference between the groups in vasopressor requirement [mean dose of ephedrine: Group D = 21.6 mg (95% CI 15.1-28.2), Group NS = 16 mg (95% CI 12.0-20.5)].\n The routine administration of dextrose 5% at a rate of 5.22 g x hr(-1) preoperatively does not affect the hypotension rate, or make it easier to treat.", "We have studied the effects of crystalloid 1 litre (lactated Ringer's) or colloid 0.5 litre (hydroxyethyl starch) preloading in 26 healthy parturients undergoing elective Caesarean section under spinal anaesthesia. Maternal placental uterine artery circulation was measured using a pulsed colour Doppler technique with simultaneous measurement of maternal haemodynamics. A high incidence of maternal hypotension was observed during spinal anaesthesia in the crystalloid group (62%) but the incidence was lower in the colloid group (38%). Central venous pressure was increased significantly in both groups after preload but decreased shortly after induction of spinal anaesthesia to baseline values. The mean pulsatility index (PI) in the uterine arteries did not change during preload or spinal block. A surprising finding was the widespread variation and some high values for the uterine artery PI after spinal anaesthesia. These individual increases in PI were transient and always returned to baseline values within 2 min. These results suggest that preloading with either solution is ineffective in preventing maternal hypotension and that changes in maternal heart rate, systolic arterial pressure and central venous pressure during spinal anaesthesia were not associated with rapid individual increases in uteroplacental vascular resistance. These changes seemed not to have any major effect, however, on the clinical condition of the newborn, as assessed by Apgar scores and umbilical artery pH values.", "To evaluate the hemodynamic effects of an intravenous (IV) ephedrine bolus given simultaneously with spinal anesthesia for cesarean delivery.\n Randomized, prospective, double-blind study.\n Tertiary-care academic medical center.\n 40 ASA physical status I and II nonlaboring women undergoing elective cesarean delivery of term, uncomplicated, singleton pregnancies.\n After a 10 mL/kg IV lactated Ringers bolus given over 15 minutes, patients simultaneously received an IV dose of 2 mL (10 mg) ephedrine or 2 mL saline, and an intrathecal dose of 12 mg (1.6 mL 0.75%) bupivacaine with 10 microg of fentanyl. Hypotension, defined as a 20% decrease in mean arterial pressure (MAP), was treated with 10-mg IV doses of ephedrine.\n Hemodynamic (heart rate and MAP) and non-invasive thoracic impedance (cardiac index, stroke index, and systemic vascular resistance index) measurements at baseline and at 1-minute intervals until the time of delivery. Total fluid, supplemental ephedrine, and Apgar scores were recorded. Data were evaluated using analysis of variance (ANOVA), ANOVA for repeated measures, and Mann-Whitney U-tests where appropriate, with p < 0.05 considered significant.\n Significant changes from baseline in MAP, systemic vascular resistance index, heart rate, and cardiac index were observed in both groups after spinal anesthesia. However, there were no differences between the ephedrine and saline groups in the incidence and severity of change from the baseline. The overall incidence of hypotension was 70% in both groups. No difference in total fluid or supplemental ephedrine use was observed.\n 10 mg of IV ephedrine given at the time of spinal anesthesia, and after a 10 mL/kg lactated Ringers fluid bolus, does not diminish the incidence or severity of hypotension in parturients undergoing cesarean delivery.", "In this study, we compared the effect of prophylactic administration of warm and cold saline against spinal anaesthesia induced hypotension in parturients undergoing elective caesarean section. One hundred and thirteen parturients with singleton pregnancies received an i.v. infusion of isotonic saline 20 mL x kg(- 1)during the 15 min before spinal injection followed by 10 mL x kg(- 1)during the 20 min after spinal injection. Fifty-seven patients were allocated to the warm saline group (37 degrees C) and 56 to the cold saline group (21 degrees C). Discomfort in the infusion arm was less in the warm saline group (P<0.01), whereas the incidence of shivering was similar in the two groups. Following induction of spinal anaesthesia, blood pressures were significantly higher in the cold saline infusion group compared to the warm saline group (P<0.05). However, the group mean difference in mean arterial pressure was only about 5 mmHg, and the amount of ephedrine administered and the incidence of clinical significant hypotension did not differ between groups. In conclusion, the temperature of the fluid used for i.v. preload and maintenance at caesarean section under spinal anaesthesia is not clinically important.", "Pre-emptive intramuscular (i.m.) vasopressors were evaluated in 108 patients undergoing elective Caesarean section under spinal anaesthesia, assigned to four groups in a randomized, double-blind, placebo-controlled study. Group 1 received pre-emptive phenylephrine 4 mg i.m., group 2 received phenylephrine 2 mg i.m., group 3 received ephedrine 45 mg i.m., while controls received an i.m. injection of saline, all given immediately after induction of spinal anaesthesia. Hypotension was defined as a 25% decrease in mean arterial pressure (MAP). Rescue intravenous (i.v.) boluses of ephedrine were given if the patient was hypotensive or reported nausea, vomiting or dizziness. The incidence of hypotension was 33% in the phenylephrine 4 mg group compared with 70% in the control and phenylephrine 2 mg groups (P=0.03), and 48% in the ephedrine 45 mg group. The phenylephrine 4 mg and ephedrine 45 mg groups had a significantly lower percentage reduction in MAP (-21 (SD 14)% and -22 (14)%) compared with controls (-32 (18)%, P=0.04). They also had a lower total dose of rescue i.v. ephedrine (15.7 (15.7) mg and 15.8 (15.6) mg) compared with controls (28.8 (20.6) mg, P=0.02). We conclude that pre-emptive i.m. phenylephrine 4 mg and ephedrine 45 mg reduce the severity of hypotension and the total dose of rescue i.v. ephedrine during spinal anaesthesia for Caesarean section.", "Twenty-four parturients undergoing elective Caesarean section were allocated randomly to have the legs wrapped with elasticated Esmarch bandages immediately following spinal anaesthesia or to serve as controls. Significant hypotension (systolic arterial pressure less than 100 mm Hg and less than 80% of baseline value) was treated with i.v. ephedrine in 5-mg boluses. Leg wrapped patients had a significantly (P = 0.0033) lower incidence (16.7%) of hypotension than controls (83.3%). Only two patients in the leg wrapped group required ephedrine compared with 10 in the control group. Systolic arterial pressure was significantly (P less than 0.05) less in control subjects at 4, 5 and 6 min following spinal injection. No patient in the leg wrapped group became hypotensive following removal of the elasticated bandages.", "This study aimed to compare low-molecular weight hydroxyethyl starch containing 1% dextrose (HES) infusion and lactated Ringer's solution (LR) in the prevention of hypotension associated with spinal anesthesia for cesarean section.\n Sixty-seven patients scheduled for cesarean section under spinal anesthesia were randomly allocated to receive either LR ( n= 35) or HES ( n= 32) infusion before cesarean delivery. Infusion of the fluid was started immediately after arrival at the operating room, through two fully open i.v. routes of 18 or 16 gauge. The two groups were compared in terms of the incidence of hypotension; ephedrine dose; cord and maternal blood gas, hemoglobin, and glucose; and Apgar scores.\n Intravenous fluid volume until delivery in the LR group was significantly greater than that in the HES group (1298 +/- 503 and 973 +/- 339 ml, respectively) in spite of the similar periods of intravenous infusion (18.1 +/- 3.9 and 18.2 +/- 4.1 min). The incidence of hypotension, and the ephedrine dose, blood gas analyses, and Apgar scores were not significantly different between the groups. The ephedrine dose correlated with the anesthesia level by spinal anesthesia (P < 0.05).\n This study did not show an advantage of HES compared with LR in the prevention of hypotension or in the reduction of ephedrine dose during cesarean section under spinal anesthesia. The anesthesia level, rather than the choice of intravenous fluid solution, might be related to the ephedrine dose.", "Maternal position during induction of intrathecal anaesthesia for caesarean section influences block height and haemodynamic stability. In a randomised study of 90 women presenting for elective caesarean section using combined spinal-epidural anaesthesia, three positions were compared--the Oxford position (group O), the right lateral to supine wedged (group R) and the sitting to supine wedged (group S). Hyperbaric bupivacaine 12.5 mg with fentanyl 12.5 microg was injected intrathecally using a needle-through-needle CSE technique. Intravenous ephedrine 6 mg was given every minute that systolic blood pressure fell below 80% of baseline. Time required for block height to reach T5 as assessed by light touch, was similar in the three groups. There were no significant differences in blood pressure although ephedrine requirements were less in group R. There were no significant differences in the incidence of maternal nausea and vomiting or in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis. Although the study failed to show any significant differences in block height between the groups, no women in group O had a block above T2 compared with three in group R and three in group S.", "Twenty parturients undergoing elective Caesarean section were allocated randomly to receive crystalloid preload 20 ml kg-1 over either 20 min or 10 min before spinal anaesthesia. Significant hypotension (systolic arterial pressure less than 100 mm Hg and less than 80% of baseline value) occurred in six of the 10 patients in the 20-min preload group and seven of 10 patients in the 10-min preload group (ns). Both groups had a significant (P less than 0.05) increase in central venous pressure during the preload period. The mean central venous pressure in the 10-min group was 11.9 mm Hg (range 6-19 mm Hg), which was significantly greater (P less than 0.05) than that in the 20-min group (mean 7.3 mm Hg, range 2-13 mm Hg). Three patients in the 10-min group had clinically unacceptable increases in central venous pressure. This study has demonstrated that rapid administration of crystalloid preload before spinal anaesthesia did not decrease the incidence or severity of hypotension, and questions the role of crystalloid preload.", "We compared the efficacy of prophylactic ephedrine infusion over fluid preloading in prevention of maternal hypotension during spinal anaesthesia for Caesarean section. Forty-six women undergoing elective Caesarean section at term were allocated randomly to receive either intravenous fluid preloading with Hartmann's solution 20 ml.kg-1 (fluid group) or prophylactic intravenous ephedrine 0.25 mg.kg-1 (ephedrine group). Moderate hypotension was defined as > or = 20% reduction in systolic blood pressure and severe hypotension as > or = 30% reduction in systolic blood pressure. Maternal uterine circulation was measured using Doppler ultrasound in 11 parturients before and after spinal anaesthesia. There was a lower incidence of severe hypotension in the ephedrine group compared with the fluid group (35% vs. 65%, p = 0.04), although the incidence of moderate hypotension was similar. Mean umbilical venous pH was higher in the ephedrine group than in the fluid group (7.33 vs. 7.29, p = 0.02) and the number of patients shivering was lower in the ephedrine group (2 vs. 9, p = 0.02). No difference was found between pre- and postspinal uterine artery pulsatility indices in either group. We conclude that prophylactic ephedrine infusion alone is at least as good as fluid preload alone in combating the hypotension associated with spinal anaesthesia for Caesarean section.", "Maternal cardiovascular changes and neonatal acid-base status, including lactate levels, were assessed in 30 healthy women undergoing elective caesarean section under spinal anaesthesia. Patients were allocated randomly to receive IV ephedrine infusion (n = 15) (5 mg.min(-1) immediately after the spinal injection or bolus administration of IV ephedrine (n = 15) (10 mg) in case of development of hypotension. Maternal and neonatal blood pressure, heart rate and acid-base status including lactate levels were compared between the groups. Systolic blood pressure in the bolus group was significantly lower when compared to the infusion group. Nausea was observed in one patient (6%) in the infusion group and nausea and vomiting were observed in 10 patients (66%) in the bolus group. Although umbilical arterial pH values were significantly lower in the bolus group, lactate levels were similar In conclusion, ephedrine infusion prevented maternal hypotension, reduced the incidence of nausea and vomiting and led to improved umbilical blood pH during spinal anaesthesia for caesarean section.", "Maternal hypotension is the most common complication following spinal anesthesia for cesarean section. This study aimed at comparing the incidence of hypotension and the need for vasopressors in patients submitted to cesarean section under spinal anesthesia following preload with either crystalloid or colloid (modified fluid gelatin).\n Participated in this prospective study 50 term pregnant patients, physical status ASA I, submitted to cesarean section under spinal anesthesia. Patients were randomly allocated into two groups receiving preload as follows: Crystalloid group, 10 mL.kg-1 lactated Ringer; Colloid group, 10 mL.kg-1 colloid (modified fluid gelatin). Control blood pressure was defined as the mean of three successive systolic blood pressure (SBP) values. SBP was measured at 1-minute intervals and 0.2 mg intravenous bolus of metaraminol was administered for SBP decrease above 10% of control blood pressure, and 0.4 mg bolus of the same drug for SBP decrease above 20% of control. Apgar score was evaluated after delivery and umbilical artery blood was sent for analysis. Modified Student's t test was used for statistical analysis and p < 0.05 was considered statistically significant.\n Hypotension 10% (100% and 100% of patients); hypotension 20% (72% and 72% of patients), nausea (4% and 8% of patients); vasopressor consumption (1.67+/- 0.89 mg and 1.88 +/- 0.74 mg) and umbilical artery pH (7.25 +/- 0.04 and 7.26 +/- 0.04), in Crystalloid and Colloid groups, respectively, were similar.\n In the conditions of this study, colloid (modified fluid gelatin) was equivalent to crystalloid (lactate Ringer) in preventing or decreasing the incidence of hypotension in patients submitted to cesarean section under spinal anesthesia.", "This study was carried out to determine whether the use of thrombo-embolic deterrent (TED) stockings, in combination with an intravenous crystalloid preload, would prevent hypotension following spinal anaesthesia for caesarean section. Fifty parturients undergoing elective caesarean section under spinal anaesthesia were randomly allocated into two groups. TED stockings were applied to the study group 1 h before spinal anaesthesia but none were applied to the control group. Both groups received a crystalloid preload of 15 ml kg(-1) over 15 min before spinal injection. Significant hypotension, defined as an absolute value of systolic arterial pressure (SAP) of less than 90 mmHg and a decrease of more than 20% from baseline SAP was treated with 3 mg bolus of ephedrine as required. The difference in SAO between the two groups was not statistically significant. In the control group, 80% of parturients required ephedrine as opposed to 56% in the TED group; a difference that was also not statistically significant.", "This study investigated the use of a Sequential Compression Device (SCD) with thigh-high sleeves and a preset pressure of 50 mm Hg that recruits blood from the lower limbs intermittently, as a method to prevent spinal hypotension during elective Caesarean section. Possible association of arterial pressure changes with maternal, fetal, haemodynamic, and anaesthetic factors were studied.\n Fifty healthy parturients undergoing elective Caesarean section under spinal anaesthesia were randomly assigned to either SCD (n=25) or control (n=25) groups. A standardized protocol for pre-hydration and anaesthetic technique was followed. Hypotension was defined as a decrease in any mean arterial pressure (MAP) measurement by more than 20% of the baseline MAP. Systolic (SAP), MAP and diastolic (DAP) arterial pressure, pulse pressure (PP), and heart rate (HR) were noted at baseline and every minute after the spinal block until delivery.\n A greater than 20% decrease in MAP occurred in 52% of patients in the SCD group vs 92% in the control group (P=0.004, odds ratio 0.094, 95% CI 0.018-0.488). There were no significant differences in SAP, DAP, HR, and PP between the groups.\n SCD use in conjunction with vasopressor significantly reduced the incidence of a 20% reduction of MAP.", "Eighty-seven pregnant mothers undergoing elective Caesarean section were randomly allocated either to the full left lateral position (n = 45) or to the supine position with 12 degrees left lateral tilt (n = 42) after a combined spinal-epidural (CSE) in the sitting position and an initial 2 min in the full right lateral position. Fewer mothers were hypotensive while in the study position [29 (64%) in lateral group vs. 38 (90%) in the tilted supine group; p = 0.03]. Mothers in the lateral group tended to become hypotensive after turning them back to the tilted supine position immediately before surgery; hence the number of mothers who were hypotensive from the insertion of the CSE until delivery were similar [36 (80%) vs. 38 (90%)]. Mothers in the lateral group needed a lower dose of ephedrine to treat their hypotension while in their study position (median (interquartile range [range]) 6 (0-12 [0-36]) mg vs. 12 (6-18 [0-36]) mg, respectively; p = 0.04) but ephedrine requirements were similar overall (12 (6-12 [0-36]) mg vs. 12 (6-18 [0-36]) mg), respectively. The full left lateral position reduces the incidence of early hypotension compared with the tilted supine position with tilt, and makes it easier to treat.", "Hypotension commonly accompanies induction of spinal anesthesia for cesarean section. To determine whether intravenous ephedrine prophylaxis would benefit prehydrated obstetrical patients presenting for elective cesarean section, we studied 30 patients randomly assigned to one of three experimental groups. All patients were preloaded with crystalloid (15 ml/kg), given spinal anesthesia and positioned with left uterine displacement (LUD). During induction, all patients received a 2 ml intravenous bolus and intravenous infusion of the study drug or placebo. The control group (n=10) received a saline bolus and saline infusion, the bolus group (n=10) received an ephedrine bolus (10 mg) and a saline infusion and the infusion group (n=10) received a saline bolus and a two-stage ephedrine infusion (20 mg over 12 min). After induction of anesthesia, systolic blood pressure decreased in the first 5 min in all groups. Hypotension occurred in 6/10 control patients, 5/10 bolus patients and 5/10 infusion patients. The amount of supplemental ephedrine required to treat hypotension did not differ among groups. Although the efficacy of ephedrine prophylaxis for hypotension associated with spinal anesthesia for elective cesarean section cannot be established by the small number of patients studied, this practice does not appear to be clinically relevant at the doses studied.", "This study was designed to compare the efficacy of 10% dextran 40 with lactated Ringer's (LR) solution in reducing the incidence and severity of hypotension after spinal anesthesia for Cesarean section.\n Sixty ASA grade I patients scheduled for Cesarean section were randomized into two groups in a double-blind fashion to receive either 500 ml of dextran 40 or 1000 ml of LR solution prior to induction of spinal anesthesia.\n The incidence of hypotension was 16 in 30 (53.3%) in the LR solution group and 8 in 30 (26.7%) in the dextran group (P < 0.05). The required dose of ephedrine for treatment of hypotension was significantly greater in the LR solution group than in the dextran group (15.5 mg versus 3.2 mg, P < 0.05). Neonatal outcome, as determined by Apgar score, was good and similar in both groups.\n We concluded that 500 ml of dextran 40 is more effective than 1000 ml of lactated Ringer's solution in reducing the incidence of hypotension induced by spinal anesthesia.", "Induction of spinal anesthesia for cesarean delivery in the left lateral (LL) decubitus position combined with intraoperative left uterine displacement may result in pooling of local anesthetic onto one side of the body. We studied the effect of the right lateral (RL) and LL decubitus positions during placement of spinal anesthesia on the intrathecal spread of 0.5% hyperbaric bupivacaine plus fentanyl in 60 term parturients. Though all parturients acquired a loss of cold sensation at T4 15 min after intrathecal injection, more parturients in the LL group than in the RL group did so at 5 min (P < 0.05). The maximum levels of sensory blockades, amounts of fluid, vasopressor, and supplementary analgesia used, and the incidence of postoperative complications were similar. We conclude that the two positions can be used equally well when hyperbaric bupivacaine and fentanyl are used in cesarean delivery under spinal anesthesia.\n We conducted a double-blinded randomized trial comparing the spread of spinal anesthesia placed with a parturient in either the right or left lateral position. There was a faster onset in the left lateral group; however, the maximum block heights and the time taken to achieve them were similar in both groups.", "To assess the safety and efficacy of 37.5 mg ephedrine i.m. in preventing hypotension associated with spinal anaesthesia for Caesarean section.\n In a double-blind randomised controlled study, 40 patients (20 in each group) were given either 37.5 mg ephedrine or placebo i.m. The following parameters were recorded: (i) blood pressure; (ii) heart rate; (iii) ephedrine i.v. supplementation; (iv) umbilical venous blood gases and neonatal Apgar scores.\n The incidence of hypertension in the study group was 30% compared with 20% for the control group (P:NS). There was no difference in mean highest blood pressure or mean highest heart rate between the groups. The incidence of hypotension was lower but not significantly lower in the study group (50%) than in the control group (80%) (P:NS). However, the incidence of delayed hypotension was only 10% in the study group patients compared with 50% in the control group patients (P < 0.05).\n Giving 37.5 mg ephedrine i.m. prior to spinal anaesthesia was not associated with reactive hypertension or tachycardia. Intramuscular ephedrine provided more sustained cardiovascular support than intravenous ephedrine.", "The effect of the head-down tilt position after induction of spinal anesthesia for cesarean delivery on blood pressure and level of sensory block was examined.\n Patients were allocated randomly into two groups, the head-down tilt group (n = 17) and the horizontal group (n = 17). In the head-down tilt group, patients were positioned with a 10 degrees head-down tilt immediately after supine positioning, while those in the horizontal group were maintained in a horizontal position. All patients received 500 mL of lactated Ringer's solution intravenously over 10 minutes prior to spinal injection, a wedge was placed under the patient's right hip, and the operating table was rotated 5 degrees in a counterclockwise direction to provide left uterine displacement. Hypotension (defined as systolic blood pressure below 100 mm Hg) was treated with 5 mg ephedrine intravenously and an increase in the infusion rate of lactated Ringer's solution. The change in systolic blood pressure was expressed as percent change from the baseline value.\n Systolic blood pressure decreased 20% at 3 minutes after spinal block in both groups but recovered to half of this decrease. The incidence of postspinal hypotension was not different between the two groups. The total amount of ephedrine and lactated Ringer's solution administered during the first 20 minutes of spinal block did not differ between the two groups nor did the extent of the cephalad spread of analgesia 20 minutes after spinal block (T4 +/- 2 vs T4 +/- 1 for the head-down and horizontal groups, respectively).\n The head-down position is concluded to have no effect on the incidence of hypotension during spinal anesthesia for cesarean delivery.", "We have tested the hypotheses that glycopyrrolate, administered immediately before induction of subarachnoid anaesthesia for elective Caesarean section, reduces the incidence and severity of nausea, with no adverse effects on neonatal Apgar scores, in a double-blind, randomized, controlled study. Fifty women received either glycopyrrolate 200 micrograms or saline (placebo) i.v. during fluid preload, before induction of spinal anaesthesia with 2.5 ml of 0.5% isobaric bupivacaine. Patients were questioned directly regarding nausea at 3-min intervals throughout operation and asked to report symptoms as they arose. The severity of nausea was assessed using a verbal scoring system and was treated with increments of i.v. ephedrine and fluids. Patients in the group pretreated with glycopyrrolate reported a reduction in the frequency (P = 0.02) and severity (P = 0.03) of nausea. Glycopyrrolate also reduced the severity of hypotension, as evidenced by reduced ephedrine requirements (P = 0.02). There were no differences in neonatal Apgar scores between groups.", "Hypotension is a common side effect of spinal anaesthesia for caesarean section. We have performed a randomised, controlled study to determine the efficacy of a sequential compression device (SCD) (Kendall) in combination with thromboembolic deterrent (TED) stockings (Kendall) to reduce the incidence of hypotension in this setting. Within 20 min of spinal injection, there was no statistically significant difference in the incidence of hypotension (defined as less than 100 mmHg and less than 80% of baseline blood pressure) (TED/SCD group 65%, control 80%, P = 0.12). However, there was a trend for those receiving TED/SCD prophylaxis to require less ephedrine to maintain normotension than the control group (median TED/SCD 3 mg, control 6 mg, P = 0.08). The administration of ephedrine deviated from protocol on a total of 46 occasions (2.3% of recordings). To try to reduce the influence of this, we reinspected our data using time to first episode of hypotension with a Kaplan-Meier survival analysis. This showed that the instantaneous risk (hazard) of developing hypotension was 1.8 (95% CI: 1.1-2.9) times higher in controls than those receiving TED/SCD prophylaxis (P = 0.02). Despite demonstrating some benefit of TED/SCD prophylaxis to prevent hypotension, we do not consider that the magnitude of this benefit warrants their routine use.", "To compare the preloading effect of 500 ml hydroxyethylstarch (HES) 10% with 1 L Lactated Ringer's solution (LR).\n In 40 healthy women undergoing elective Cesarean section HES, 500 ml (n = 20), or LR, IL (n = 20), was administered during 10 min before spinal anesthesia. The incidence of hypotension, (systolic blood pressure < 80% of baseline and < 100 mm Hg), and the amount of ephedrine used to treat it were compared. Also, the incidence of nausea and/or vomiting were recorded. Neonatal outcome was assessed using Apgar scores and umbilical venous and arterial blood gases.\n The incidence of hypotension was higher in the LR than in HES group (80% vs 40%). Mean minimum systolic blood pressure was lower in the LR than in the HES group (86.1 +/- 12.7 mm Hg vs 99.6 +/- 9.7 mm Hg P < 0.05). Systolic blood pressure < 90 mmHg occurred in two of 20 patients (10%) who received HES vs 11 of 20 patients (55%) who received LR (P < 0.05). More doses of ephedrine were required to treat hypotension in the LRthan in the HES group (35.3 +/- 18.4 mg vs 10.6 +/- 8.6 mg; P < 0.05). The incidence of nausea and/or vomiting was lower in the HES than in the crystalloid group. Neonatal outcome was good and similar in both groups.\n Preloading patients undergoing elective Cesarean section with 500 ml HES 10%, decreases the incidence and severity of spinal-induced hypotension more than preloading with 1 L of LR solution.", "One hundred women were randomly allocated to the left lateral, Oxford or sitting position for induction of combined spinal-epidural anaesthesia for Caesarean section using 2.5 ml hyperbaric bupivacaine 0.5% and 10 mug fentanyl. Women in the left lateral were then turned to the right lateral position; women in the Oxford position were turned to the same position on their opposite side; and women in the sitting group were turned to the supine left tilt position. Women remained in these positions until ready for surgery, which was conducted in the supine position with a wedge placed under the right hip. Ephedrine requirements before re-positioning for surgery were less in the sitting position than in the other two positions: median (IQR [range]) doses for the lateral, Oxford and sitting groups were 21 (12-30 [6-48]), 18 (7.5-24 [6-48]) and 12 (6-21 [6-42]) mg, respectively; p = 0.04. Sensory block to touch sensation at the T5 dermatomal level was most quickly achieved in the lateral position with median (IQR [range]) block onset times for the lateral, Oxford and sitting groups of 9 (6-13 [4-30]), 15.5 (9-22 [4-34]) and 14 (9-18[6-36]) min, respectively; p = 0.004. In the Oxford position, more epidural catheters required dosing to achieve a sensory block of T5 before surgery: the number of patients (proportion) bolused in the lateral, Oxford and sitting groups was 1 (3%), 7 (22%) and 1 (3%), respectively; p = 0.01. We did not demonstrate any advantage in using the Oxford position for combined spinal-epidural anaesthesia for elective Caesarean section.", "Hypotension associated with spinal anesthesia for cesarean section is still a clinical problem. Colloid solutions seem preferable to crystalloid solutions for preloading. In most studies the overall rate of hypotension is reported. Few studies have, however, investigated the maternal and neonatal consequences of different levels of maternal hypotension.\n In this randomized, double-blinded study 110 patients presenting for elective cesarean section received either 1000 ml acetated Ringer's solution or 1000 ml 3% dextran 60 solution immediately before spinal anesthesia. The effect on overall hypotension, clinically significant hypotension (hypotension associated with maternal discomfort defined as nausea, retching/vomiting, dizziness or chest symptoms) and severe hypotension (systolic arterial pressure <80 mmHg) was studied.\n Dextran reduced the incidence of overall hypotension from 85 to 66% (P=0.03), reduced the incidence of clinically significant hypotension from 60 to 30% (P=0.002) and reduced the incidence of severe hypotension from 23 to 3.6% (P=0.004) compared to Ringer's solution. There were neither differences in neonatal outcome between treatment groups nor between neonates grouped after severity of maternal hypotension.\n Clinically significant hypotension seems to be a more suitable outcome variable than overall hypotension. The protective effect of the colloid solution increased with increased severity of hypotension.", "The endogenous release of the vasoactive peptides atrial natriuretic peptide and endothelin-1 may modify maternal haemodynamic responses to a rapid intravenous volume load used to prevent hypotension at elective Caesarean delivery under spinal anaesthesia. Twenty-two healthy pregnant women were examined during elective Caesarean section at term pregnancy. They were randomly assigned to receive either 2000 ml of Ringer lactate solution (crystalloid group) or 500 ml of 6% hydroxyethyl starch + 1000 ml of Ringer lactate solution (colloid group). The mean (SEM) concentration of atrial natriuretic peptide in plasma increased from 10.9 (1.5) to 24.7 (5.1) pmol.l-1 during crystalloid infusion and from 10.3 (1.4) to 28.2 (5.6) pmol.l-1 during colloid infusion. A slight decrease in endothelin-1 levels was found during colloid infusion. A significant increase in the release of atrial natriuretic peptide in response to volume load may decrease vascular tone and initiate diuresis, thereby attenuating the effect of volume load on blood pressure during elective Caesarean delivery.", "The role of crystalloid preloading to prevent hypotension associated with spinal anesthesia in parturients during cesarean section has been challenged. Direct measurement of blood volume should provide insight regarding the volume-expanding effects. The aim of the current study was to clarify the effects of volume preload with either crystalloid or colloid solution on the changes in blood volume of parturients undergoing spinal anesthesia for cesarean section.\n Thirty-six healthy parturients scheduled for elective cesarean section during spinal anesthesia were allocated randomly to one of three groups receiving 1.5 l lactated Ringer's solution (LR; n = 12), 0.5 l hydroxyethylstarch solution, 6% (0.5 l HES; n = 12), and 1.0 l hydroxyethylstarch solution, 6% (1.0 l HES; n = 12), respectively. Blood volume and cardiac output were measured before and after volume preloading with indocyanine green (ICG), and the indocyanine green blood concentrations were monitored by noninvasive pulse spectrophotometry.\n After volume preload, the blood volume significantly increased in all three groups (P < 0.01). The volume of infused solution remaining in the vascular space in the LR, 0.5-l HES, and 1.0-l HES groups were 0.43+/-0.20 l, 0.54+/-0.14 l, and 1.03+/-0.21 l, respectively, corresponding to 28% of lactated Ringer's solution and 100% of hydroxyethylstarch solution infused. Significant increases in cardiac output were observed in the 0.5-l and 1.0-l HES groups (P < 0.01). A significant correlation between the percentage increase in blood volume and that of cardiac output was observed by volume preloading (r2 = 0.838; P < 0.001). The incidence of hypotension was 75% for the LR group, 58% for the 0.5-l HES group, and 17% for the 1.0-l HES group, respectively.\n The incidence of hypotension developed in the 1.0-l HES group was significantly lower than that in the LR and 0.5-l HES groups, showing that greater volume expansion results in less hypotension. This result indicates that the augmentation of blood volume with preloading, regardless of the fluid used, must be large enough to result in a significant increase in cardiac output for effective prevention of hypotension.", "Twenty-six parturients scheduled to receive spinal anaesthesia for caesarean section were randomized to receive either isotonic saline 750 ml plus 20 ml/kg (group A) or 750 ml plus 500 ml (group B) before subarachnoid administration of bupivacaine 13 mg. Ephedrine 0.15 mg/kg i.v. followed by an infusion 0.4 mg.kg(-1) h(-1) were then administered in group B. In both groups ephedrine 10 mg/min i.v. was given if the mean arterial blood pressure decreased more than 10 mmHg. Despite the fluid preload and large doses of ephedrine noted {median (range), group A 30 mg (10-80), group B 92 mg (25-194)}, hypotension, sometimes accompanied by nausea, still occurred. Mean maternal arterial was significantly lower in group A than in group B 5-10 min after induction of spinal anaesthesia (P < 0.05). There was no difference in the frequency of nausea or vomiting, Apgar score, or pH in umbilical cord blood. One neonate in group A and 2 in group B were acidotic. In conclusion, a reduced volume loading could be compensated with an increased ephedrine administration after induction of spinal anaesthesia, without increasing the incidence of hypotension or other maternal or neonatal complications. However, the fluid volumes and/or ephedrine doses used were not sufficient to prevent hypotension altogether.", "The study tested the hypothesis that the incidence of hypotension during spinal anaesthesia for caesarean section is less in parturients who remain in the sitting position for 3 min compared with parturients who are placed in the modified supine position immediately after induction of spinal anesthesia.\n Spinal anaesthesia was induced with the woman in the sitting position using 2.8 ml hyperbaric bupivacaine 0.5% at the L(3-4) or L(2-3) interspace. Ninety-eight patients scheduled for elective caesarean section under spinal anaesthesia were randomised to assume the supine position on an operating table tilted 10 degrees to the left (modified supine position) immediately after spinal injection (group 0, n=52) or to remain in the sitting position for 3 min before they also assumed the modified supine position (group 3, n=46). Isotonic saline 2-300 ml was given intravenously over 15 min before spinal injection followed by 15 ml/kg over 15-20 min after induction of spinal anaesthesia. If the systolic blood pressure decreased to less than 70% of baseline or to less than 100 mmHg or if there was any complaint of nausea, ephedrine was given in 5 mg boluses intravenously every 2 min.\n The blood pressure decreased significantly in both groups following spinal injection (P<0.001). Blood pressure variations over time differed significantly between the two groups (P<0.05). However, the incidence of maternal hypotension before delivery was similar in the two groups. The difference was caused by the time to the blood pressure nadir being significantly shorter in group 0 compared with group 3 (9.1+/-4.5 min vs. 11.7+/-3.7 min, P<0.01). Similar numbers of patients received rescue with ephedrine before delivery: 35 (67%) in group 0 vs. 26 (57%) in group 3 (NS). The mean total dose of ephedrine before delivery was 10.9 mg in group 0 vs. 9.2 mg in group 3 (NS). There were no differences in neonatal outcome between the two groups.\n At elective caesarean section, a 3-min delay before supine positioning does not influence the incidence of maternal hypotension after induction of spinal anaesthesia in the sitting position with 2.8 ml of bupivacaine 0.5% with 8% dextrose.", "Sixty healthy women undergoing elective Caesarean section were randomly allocated to either a measured 15 degrees left table tilt position (n = 31) or full left lateral position (n = 29) for a 15-min period after spinal blockade. Arm and leg blood pressure, ephedrine requirements, symptoms, fetal heart rate, cord gases and Apgar scores were recorded. Mean ephedrine requirements and incidence of hypotension were similar in the two groups. Arm systolic arterial pressure over time was similar in both groups, but leg systolic arterial pressure over time was significantly lower in the tilt group (p < 0.001); the mean leg systolic arterial pressure was lower for all 15 sequential recordings in the tilt group, reaching statistical significance (p < 0.05) at 4, 5, 6 and 8 min. Differences in maternal nausea, vomiting and bradycardia and fetal outcome were not statistically significant. Following spinal anaesthesia, even a true 15 degrees left table tilt position is associated with aortic compression.", "To evaluate the effectiveness of prophylactic ephedrine for the prevention of hypotension associated with spinal anesthesia, 50 parturients undergoing cesarean delivery received either ephedrine 5 mg or saline IV in a double-blinded fashion immediately after the induction of spinal anesthesia. Spinal anesthesia was performed with hyperbaric bupivacaine 6.6 mg combined with sufentanil 3.3 microg as part of a combined spinal-epidural technique. All patients received 1000 mL of lactated Ringer's solution and 500 mL of hydroxyethylstarch 6% before the spinal injection. Additional ephedrine boluses (5 mg) were administered IV when the systolic blood pressure or heart rate decreased by more than 30% from baseline values, when systolic blood pressure became <100 mm Hg, or when patients complained of nausea or feeling faint. The height of the block was equal in the groups; however, more patients in the placebo group were found to develop hypotension (58% vs 25%, P < 0. 05). Only 2 (8%) patients in the ephedrine group developed hypotension with systolic blood pressure values <90 mm Hg, whereas 10 patients (42%) in the saline group experienced hypotension of this severity (P < 0.05). In addition, there was a higher incidence of nausea in the placebo-treated patients. The total amount of ephedrine administered did not differ between groups. These findings suggest that the incidence and severity of hypotension are significantly reduced by the IV administration of a prophylactic dose of 5 mg ephedrine in patients receiving small-dose spinal anesthesia for cesarean delivery.\n Ephedrine is the drug most often used to correct hypotension during spinal anesthesia for cesarean delivery in healthy patients. A single IV dose of 5 mg decreases the occurrence and limits the severity of hypotension in prehydrated subjects receiving a small-dose spinal local anesthetic-opioid combination.", "Nausea and vomiting occur frequently during cesarean section under spinal anesthesia. Metoclopramide reduces intraoperative nausea and vomiting, but not without potential side effects. Acupressure, a noninvasive variation of acupuncture that involves constant pressure on the wrist, has been suggested as an alternative method to prevent nausea and vomiting. The aim of this study was to compare acupressure and intravenous (IV) metoclopramide for the prevention of nausea and vomiting during elective cesarean section under spinal anesthesia. Seventy-five patients were studied in a randomized, prospective, double-blind comparative trial. Group I patients received acupressure bands + 2 mLIV saline, Group II patients received placebo wrist bands + 10 mg IV metoclopramide, and Group III patients received placebo wrist bands + 2 mL IV saline. Patients who received either acupressure or metoclopramide prior to initiation of spinal anesthesia for cesarean section had much less nausea than patients in the placebo group. Acupressure is an effective, non-pharmacologic method to reduce intraoperative nausea during elective cesarean section in the awake patient." ]

[ "11789238" ]

[ "[Clinical study on shenmai injection in promoting postoperative recovery in patients of breast cancer]." ]

[ "To investigate the effect of Shenmai injection in promoting postoperative recovery of patients with breast cancer.\n Eighty postoperative patients of breast cancer were selected and divided into two groups, the treated group (40 cases) was given intravenous Shenmai injection for 7 days and compared with the control group (40 cases) in wound healing time, postoperative drainage volume, complication and blood picture, and the NK cell, T-lymphocyte subsets (CD3, CD4, CD8), were compared before and after treatment.\n The wound healing time and postoperational complication in the treated group were less than those in the control group significantly. There was no difference between the two groups in WBC and platelet count, but the recovery of hemoglobin in the treated group was quicker than that in the control group significantly (P < 0.05), as comparing with the control group, the NK cell, CD4, CD4/CD8 ratio in the treated group were elevated faster than those in the control group significantly (P < 0.05).\n Shenmai injection was beneficial to the recovery of postoperative patients of breast cancer, to reducing the occurrence of complication and was favorable to conduct postoperative chemotherapy smoothly." ]

[ "17662757", "16204446", "15625793", "12670617", "7595873", "10753339", "19045972" ]

[ "Use of a self-help book with weekly therapist contact to reduce tinnitus distress: a randomized controlled trial.", "Psychophysiologic treatment of chronic tinnitus: a randomized clinical trial.", "Treating chronic tinnitus: comparison of cognitive-behavioural and habituation-based treatments.", "The management of chronic tinnitus: comparison of an outpatient cognitive-behavioral group training to minimal-contact interventions.", "The management of chronic tinnitus--comparison of a cognitive-behavioural group training with yoga.", "The Psychological Management of Tinnitus: Comparison of a Combined Cognitive Educational Program, Education Alone and a Waiting-List Control.", "Biofeedback-based behavioral treatment for chronic tinnitus: results of a randomized controlled trial." ]

[ "Tinnitus distress can be reduced by means of cognitive-behavior therapy (CBT). To compensate for the shortage of CBT therapists, we aimed, in this study, to investigate the effects of a CBT-based self-help book guided by brief telephone support.\n Seventy-two patients were randomized either to a self-help book and seven weekly phone calls or to a wait-list control condition, later on receiving the self-help book with less therapist support. The dropout rate was 7%. Follow-up data 1 year after completion of treatment were also collected (12% dropout). The Tinnitus Reaction Questionnaire (TRQ) was the main outcome measure, complemented with daily ratings of tinnitus and measures of insomnia, anxiety, and depression.\n On the TRQ, significant reductions were found in the treatment group both immediately following treatment and at 1-year follow-up. In the treatment group, 32% reached the criteria for clinical significance (at least 50% reduction of the TRQ) compared to 5% in the wait-list group. Directly after treatment, two out of five measures showed significant differences in favor of the treatment with more therapist support compared with the group who, after their waiting period, received little therapist support. The self-help treatment was estimated to be 2.6 (seven phone calls) and 4.8 (one phone call) times as cost-effective as regular CBT group treatment.\n Guided self-help can serve as an alternative way to administer CBT for tinnitus. Preliminary results cast some doubts on the importance of weekly therapist contact. The effect size was somewhat smaller than for regular CBT, but on the other hand, the self-help seems far more cost-effective. Future studies should compare treatment modalities directly and explore cost-effectiveness more thoroughly.", "Tinnitus seems to be associated with psychophysiological over-activation (e.g., of head and shoulder muscles). Therefore we aimed to develop and evaluate a new intervention program including a psychophysiological approach.\n Forty-three tinnitus sufferers were randomized to 2 groups, one receiving a psychophysiologically oriented intervention lasting 7 intervention sessions (plus 2 assessment sessions), whereas the other group waited for a comparable time period. Afterward, patients on the waiting list also received the intervention. Physiological variables were muscle activity of head and shoulders and electrodermal activity. Psychological assessments took place at pretreatment, post-treatment, and 6 months later. Follow-up data were available from 95% of participants. Major outcome variables were self-rating scales (e.g., tinnitus annoyance assessed by the Tinnitus Questionnaire), and diary data (self-control, daily time of perceiving the tinnitus).\n On most tinnitus specific variables, patients in the treatment group improved significantly more than patients on the waiting list. Main effect sizes for tinnitus-specific variables were up to 0.89. Muscle reactivity of head muscles at the beginning predicted significant treatment effects.\n Compared with meta-analytical reviews of psychological interventions for tinnitus sufferers, the presented treatment is brief and in the upper range of effectiveness.", "Using a randomized control group trial the long-term efficacy of a habituation-based treatment as conceived by Jastreboff, and a cognitive-behavioural tinnitus coping training were compared. An educational intervention was administered as a control condition. Both treatments were conducted in a group format (habituation-based treatment, 5 sessions; tinnitus coping training, 11 sessions). Educational intervention was delivered in a single group session. Patients were categorized according to their level of disability due to tinnitus (low, high), age and gender and then randomly allocated to the treatment conditions (habituation-based treatment, n = 30; tinnitus coping training, n = 27; educational intervention, n = 20). Data assessment included follow-ups of up to 21 months. Several outcome variables including disability due to tinnitus were assessed either by questionnaire or diary. Findings reveal highly significant improvements in both tinnitus coping training and habituation-based treatment in comparison with the control group. While tinnitus coping training and habituation-based treatment do not differ significantly in reduction of tinnitus disability, improvement in general well-being and adaptive behaviour is greater in tinnitus coping training than habituation-based treatment. The decrease in disability remains stable throughout the last follow-up in both treatment conditions.", "Using a randomized group design, the efficacy of an outpatient cognitive-behavioral Tinnitus Coping Training (TCT) was compared to two minimal-contact (MC) interventions.\n TCT was conducted in a group format with 11 sessions (total n=43). One MC [MC-E (education), n=16] consisted of two group sessions in which education on tinnitus was presented and self-help strategies were introduced. The second MC [MC-R (relaxation), n=16] comprised four sessions. Besides education, music-supported relaxation was suggested as self-help strategy and audiotapes with relaxing music were provided. Furthermore, a waiting-list control group was installed (WC, n=20). Data were assessed at baseline (pretherapy) and at posttherapy period. Only TCT was additionally evaluated at a 6-month and a 12-month follow-up. Several outcome variables (e.g., awareness of tinnitus) were recorded in a tinnitus diary. Tinnitus coping and disability due to tinnitus were assessed by questionnaires. Subjective ratings of improvement were also requested from the patients. Furthermore, inventories of psychopathology were given to the patients.\n Findings reveal highly significant improvements in TCT in comparison to the control group (WC). MC interventions do not differ significantly from each other, but are superior to WC in a few domains of outcome. Outcome in TCT is somewhat superior to combined MC interventions in two domains of data, but not regarding disability reduction. Effect sizes, nevertheless, indicate distinct differences in degree of improvement, with TCT achieving the best results.\n A sequential scheme for the treatment of chronic tinnitus is discussed on the basis of cost-effectiveness considerations.", "Two non-medical treatment strategies for chronic idiopathic tinnitus were evaluated in a randomized control group design. A cognitive-behavioural tinnitus coping training (TCT) was developed and compared to yoga and a self-monitoring control condition. Forty-three chronic tinnitus patients, were assessed at baseline, directly after therapy, and at 3 months follow-up. For evaluation, differential psychoacoustic variables were registered, a tinnitus diary as well as the Tinnitus Questionnaire and different measures of general well-being were used. Statistical analyses showed effects favouring the TCT treatment in comparison to the control and yoga treatment. The TCT-treated patients reported more satisfaction with the training than the yoga group. Participants in the self-monitoring control group were treated either by TCT or yoga after a waiting period. The outcome in this group was even better than in the experimental groups while yoga again showed rather poor effects.", "Sixty subjects with chronic tinnitus were randomly allocated to one of three experimental conditions: (1) cognitive coping skills training (attention diversion, imagery training and thought management skills) combined with education. (2) education-only, or (3) waiting-list control. The two treatment groups improved significantly more than the waiting-list control on measures of frequency of use of coping strategies, benefits derived from the use of coping strategies, irrational beliefs and knowledge about tinnitus. Subjects who received the combined cognitive/education intervention demonstrated significantly greater reductions in distress and handicaps associated with tinnitus, and engagement in dysfunctional cognitions, than the subjects who received education alone. No significant effects were obtained on measures of depression, locus of control, or on daily ratings of subjective loudness, noticeability or bothersomeness of the tinnitus. At the 12-month follow-up, the differential treatment effects had dissipated. Although the treatment resulted in statistically significant effects, the size of the clinical effects is rather modest. Implications for the further development of treatment techniques are discussed.", "Many tinnitus sufferers believe that their tinnitus has an organic basis and thus seek medical rather than psychological treatments. Tinnitus has been found to be associated with negative appraisal, dysfunctional attention shift, and heightened psychophysiological arousal, so cognitive-behavioral interventions and biofeedback are commonly suggested as treatments. This study developed and investigated the efficacy of a biofeedback-based cognitive-behavioral treatment for tinnitus. In total, 130 tinnitus patients were randomly assigned to an intervention or a wait-list control group. Treatment consisted of 12 sessions of a biofeedback-based behavioral intervention over a 3-month period. Patients in the wait-list group participated in the treatment after the intervention group had completed the treatment. Results showed clear improvements regarding tinnitus annoyance, diary ratings of loudness, and feelings of controllability. Furthermore, changes in coping cognitions as well as changes in depressive symptoms were found. Improvements were maintained over a 6-month follow-up period in which medium-to-large effect sizes were observed. The treatment developed and investigated in this study is well accepted and leads to clear and stable improvements. Through demonstration of psychophysiological interrelationships, the treatment enables patients to change their somatic illness perceptions to a more psychosomatic point of view." ]

[ "18398081", "16437657", "8628335", "8858747" ]

[ "Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials.", "Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study.", "Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease.", "Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group)." ]

[ "Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority.\n To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease.\n Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively.\n Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted.\n Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease.\n For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease.\n In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease.\n clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.", "To assess the value of long-chain omega-3 fatty acids (FAs) supplementation in addition to amino-salicylic-acid (5-ASA) in pediatric patients with Crohn's disease (CD).\n Thirty-eight patients (20 males and 18 females, mean age 10.13 years, range 5-16 years) with CD in remission were randomized into two groups and treated for 12 mo. Group I (18 patients) received 5-ASA (50 mg/kg/d)+ omega-3 FAs as triglycerides in gastro-resistant capsules, 3 g/d (eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g). Group II (20 patients) received 5-ASA (50 mg/kg/d)+olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment.\n The number of patients who relapsed at 1 year was significantly lower in group I than in group II (P<0.001). Patients in group I had a significant increase in the incorporation of EPA and DHA (P<0.001) and a decrease in the presence of arachidonic acids.\n Enteric-coated omega-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD.", "Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects.\n We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes.\n Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7).\n In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.", "There is no established therapy for maintaining remission in patients with Crohn's disease. Following different suggestions from the literature, two potential interventions for maintaining remission were tested against placebo, using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet (84 g/day).\n A total of 204 patients were recruited after they had had an acute relapse. After remission (CDAI < or = 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose prednisolone was given to all patients for the first 8 weeks of intervention. CDAI and an acute-phase protein (CRP) were used as criteria for a relapse.\n The proportion of patients without relapse within a year were similar in the placebo and active treatment group (intention-to-treat analysis: placebo, 30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients did gain benefit (53%; p = 0.023) for as long as they maintained the diet. However, intention-to-treat analysis (diet group, 40%) did not show a noticeable difference when compared with placebo.\n Omega-3 fatty acids did not show an effect on extending the remission in Crohn's disease. For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet." ]

[ "9419092", "10888995" ]

[ "Microscopic tonsillectomy: a double-blind randomized trial.", "Postoperative tonsillectomy pain in pediatric patients: electrocautery (hot) vs cold dissection and snare tonsillectomy--a randomized trial." ]

[ "To evaluate microsurgical bipolar cautery tonsillectomy (TEmic) by comparing it with traditional blunt dissection tonsillectomy (TEtrad).\n A double-blind prospective randomized trial with stratification in two age groups.\n 200 consecutive patients undergoing tonsillectomy for tonsillar hypertrophy, or recurrent or chronic tonsillitis.\n Duration of surgery, intraoperative bleeding, daily postoperative pain and otalgia, postoperative bleeding episodes.\n Duration of surgery and operative bleeding were evaluated by the anesthesiologist. The patients were instructed to record daily pain and otalgia. Final postoperative evaluation was done by a different physician, blinded to the surgical technique.\n Mean intraoperative bleeding was 12 ml for TEmic and 36 ml for TEtrad (P < 0.001). Mean duration of surgery was 37 minutes for TEmic and 36 minutes for TEtrad (NS). Otalgia was present in 41% of TEmic patients and 69% of TEtrad patients (p < 0.001). Daily postoperative pain was lower in the TEmic group than it was in the TEtrad group for the entire study period (10 days). Postoperative hemorrhage was present in three TEmic patients (3%) and in eight TEtrad patients (8%), a difference that did not reach significance (p > 0.1).\n Microsurgical bipolar cautery tonsillectomy compares favorably with traditional techniques in terms of intraoperative bleeding, postoperative pain, otalgia, and hemorrhage. This technique combines the hemostatic advantage of cautery dissection, the excellent visualization achieved by a microscope, and, with the use of a video, greatly improves the physician's ability to teach how to perform a tonsillectomy.", "To determine the effect of the method of tonsillectomy on postoperative pain in pediatric patients.\n Prospective, randomized, single-blind, controlled clinical trial.\n A university pediatric hospital in Aberdeen, Scotland.\n A volunteer sample of 54 children, aged 3 to 12 years, with recurrent tonsillitis or symptomatic adenotonsillar hypertrophy. Two patients withdrew consent.\n Twenty-six children underwent a nonelectrical (ie, cold) dissection tonsillectomy with cold steel instruments, 5 of whom also had adenoidectomy by curettage. Monopolar diathermy forceps were used for tonsillar bed hemostasis. Twenty-four children had electrocautery (ie, hot) dissection tonsillectomy, 7 of whom underwent adenoidectomy by curettage without a suction coagulator.\n Postoperative analgesic consumption, time to regain normal diet and activity levels, and complications.\n Patients who underwent hot dissection tonsillectomy showed no difference in time to first drink or analgesic use within the first 24 postoperative hours compared with children undergoing cold nonelectrical dissection tonsillectomy. The hot dissection tonsillectomy group took 7.5 (95% confidence interval [CI], 1-14.1) more doses of analgesics than the cold dissection group over the next 12 days (P<.05). The hot dissection tonsillectomy group took 2.5 more days than the cold dissection tonsillectomy group to regain normal diet (P<.05). Thirteen children (54%; 95% CI, 34-74) in the hot dissection tonsillectomy group and 6 (23%; 95% CI, 7-39) in the cold dissection tonsillectomy group sought outpatient care for throat pain, otalgia, poor diet, pyrexia, and/or bleeding (P<.05). Throat pain delayed in onset or of prolonged duration affected 9 children (38%; 95% CI, 19-57) in the hot dissection tonsillectomy group as opposed to 3 children (12%; 95% CI, 0-24) in the cold dissection tonsillectomy group (P<.05).\n Hot dissection tonsillectomy increases morbidity in pediatric patients in the recovery period following hospital discharge." ]

[ "1533504", "2959900", "1386071", "2959901", "6230059", "1437435" ]

[ "Bronchodilators for treatment of mild bronchiolitis: a factorial randomised trial.", "Use of nebulized bronchodilators in infants under 1 year of age: analysis of four forms of therapy.", "Treatment of acute wheezing and dyspnea attacks in children under 2 years old: inhalation of fenoterol plus ipratropium bromide versus fenoterol.", "Bronchodilator effect of fenoterol and ipratropium bromide in infants with acute wheezing: use of MDI with a spacer device.", "Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life.", "Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis." ]

[ "A randomised double blind trial was conducted to determine the efficacy of inhaled bronchodilators, salbutamol and ipratropium bromide, compared with placebo in the treatment of bronchiolitis. Patients, who were 2 months to 2 years of age and without underlying cardiac or pulmonary disease, received drug 1 (salbutamol or saline placebo) followed one hour later by drug 2 (ipratropium bromide or placebo). Both agents were administered every four hours. The patients were allocated to one of four groups according to a factorial design. The four groups were similar in demographic characteristics, initial oxygenation, and clinical score. The change in oxygen saturation of recipients of both agents was significantly better than that of recipients of salbutamol alone or ipratropium bromide alone. This change, however, was not statistically different from that of the control group. No difference was observed in the clinical score or hospital duration. Inhaled bronchodilators did not improve the condition of hospitalised mild bronchiolitis.", "The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing (AW). Seventy-nine infants less than one year of age were randomly assigned to one of five groups. Group 1 received nebulized fenoterol plus ipratropium bromide, group 2 fenoterol, group 3 fenoterol plus steroids, and group 4 aminophylline, IV, plus steroids and oral fenoterol; the control group, or group 5, received nebulized normal saline solution. Clinical evaluation was done by means of a scoring system. The effectiveness of treatments was estimated by a score decrease in the first 24 hours, by the percentage of patients whose scores did not decrease during the same period, and by the number of days in the hospital. All infants had significantly decreased scores, except those in the control group; the aminophylline group included a greater percentage of patients who did not abate their scores, and they stayed in the hospital for more days than those in the other groups. The fenoterol group had the shortest hospital stay. All four treatments produced objective clinical improvement in bronchial obstruction. However, the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day, and they resulted in shorter hospitalization.", "Two treatment regimens for the initial treatment of acute wheezing were evaluated in 61 wheezing infants. Thirty-one patients received fenoterol (F) (0.1 mg/kg) and placebo (P) and 30 patients received fenoterol (F) (0.1 mg/kg) plus a fixed dose of ipratropium bromide (IB) (50 micrograms). Both groups received the drugs by inhalation using an ultrasonic nebulizer and face mask. A clinical score system based on wheezing and rib cage retraction was established and evaluations were performed before and at 15, 30, and 45 minutes after treatment. After the last evaluation based on the clinical score, it was decided whether to repeat or not to repeat the treatment. Our results showed that a combination of a beta agonist and ipratropium bromide (FB) was more effective than a beta agonist alone (F) in reducing wheezing and dyspnea during an acute attack (63.4 versus 25.8%; p less than 0.05).", "Twenty-eight infants admitted to Exequiel González Cortes Children's Hospital because of acute wheezing (AW) were randomly assigned to three study groups. Fenoterol (FNT), ipratropium bromide (IB), and placebo were administered respectively to children in the different groups by means of metered dose inhalers (MDI) with spacers, using doses of 3 puffs every hour, for 4 hours. The degree of bronchial obstruction was assessed clinically and scored with the single-blind method every hour prior to each treatment. The criterion of a bronchodilator effect was a significant decrease in the degree of bronchial obstruction at subsequent scorings. The scores of the three groups were compared using the Student's t test for matched samples. The same test was also applied to the independent samples for determining the superiority of one treatment, FNT or IB, over the other. The results indicated a significant decrease in the scores of the groups receiving FNT and IB (P less than 0.05); this did not occur in the group in which placebo was used. FNT produced a more rapid and sustained effect than IB (P less than 0.05). Significant bronchodilator effect was obtained in infants with AW when repeated doses of FNT or IB were administered with MDI and spacers. This effect was significantly greater in the group treated with FNT.", "In a double blind crossover trial, we compared sodium cromoglycate, ipratropium bromide, and water in 23 asthmatic children less than 2 years old (mean age 11.8 months). Each child received nebulised solutions containing 20 mg of sodium cromoglycate, 250 micrograms of ipratropium bromide, or 2 ml water three times a day for three two month periods. Daily symptom scores did not show significant differences between the treatments but parental preferences indicated that both sodium cromoglycate and ipratropium bromide were superior to placebo. Sodium cromoglycate was prophylactic and was more likely to help the older patients. Ipratropium bromide produced an immediate clinical benefit and the response was not age dependent. We were unable to pick responders from non-responders on the basis of lung function tests performed on a routine outpatient basis. Both ipratropium bromide and sodium cromoglycate help some but not all asthmatic children aged less than 2 years.", "Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of \"nonresponders\" and \"clear responders\" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "8378366", "9882083", "6996933", "10235419", "7984640", "2361721" ]

[ "Comparative study of ketorolac and dipyrone in the treatment of postoperative pain.", "Clinical comparison of dexketoprofen trometamol and dipyrone in postoperative dental pain.", "A double-blind comparison of parenteral dipyrone and pethidine in the treatment of post-operative pain.", "Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain.", "Comparative study of ketorolac and dipyrone administered orally in the treatment of postoperative pain.", "A comparison of four analgesics in post-episiotomy pain." ]

[ "nan", "A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post dose to the end of the 6-h observation period, both doses of dexketoprofen trometamol had higher pain relief scores than dipyrone: Between 3 and 6 h the differences were statistically significant. In addition, peak measures (PIDmax and PARmax) were statistically superior after both doses of dexketoprofen trometamol compared to dipyrone. The overall efficacy assessed at the end of the first-dose phase was rated as good or excellent by 90%, 83.3%, and 70% of patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The number of patients who required remedication during the 6-h period was significantly lower in both dexketoprofen groups. Repeated-dose data were also obtained. No significant differences were found in the efficacy after repeated doses, the number of doses taken, or the mean time elapsed between doses. The overall efficacy at the end of the repeated-dose phase was rated as good or excellent by 84.2%, 66.7%, and 70% of patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The frequency of adverse events was similar for all treatments and no serious adverse events were reported during the study.", "A double-blind trial was carried out in 100 patients with moderate to severe post-operative pain to compare the analgesic effectiveness over a 6-hour period of single intramuscular injections of 2.5 g dipyrone and 100 mg pethidine. Maximum pain relief was seen 2 hours after drug administration in both groups and there was no statistically significant difference in responses. No side-effects were reported.", "The objective of this single-center, single-dose, double-blind randomized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels (25 mg or 50 mg) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain.\n The study was designed with a sample size of 69 patients per treatment for a total of 276 patients. However, due to administrative changes at the site, the study was prematurely terminated; thus only 108 patients (26 to 28 patients per treatment), 18 years or older, with severe postepisiotomy pain were randomized to one of the four treatments. Treatments were assessed over a 6-hour period using standard scales for pain intensity and pain relief and a number of derived variables based on these data. Since the study medications were not identical in appearance, the preparation and administration of the study medication, and the observation of the patient, were carried out by two different individuals to maintain double-blind conditions.\n All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores. The global rating was assessed as \"good\" or \"excellent\" by over 75% of the patients in the active treatment groups compared to 7.4% of the patients in the placebo group. Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg.\n Ketoprofen 25 mg or 50 mg, and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery, as well as episiotomy. This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain. All treatments were well tolerated. No adverse events were reported.", "nan", "This study was conducted to compare the analgesic efficacy of four commonly used analgesics namely ibuprofen, analgin, paracetamol and aspirin in post-episiotomy pain. The subjects were healthy postpartum women on the obstetric service of Goa Medical College, each of whom received only one experimental medication. Subjective reports were used as indices of pain intensity or relief. Ibuprofen was found to be the most effective analgesic in post-episiotomy pain followed by analgin and paracetamol in that order. Surprisingly, aspirin was found to be no better than placebo." ]

[ "18471513", "12542598", "9824265", "18471512", "17939047" ]

[ "A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome.", "Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.", "Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome.", "Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study.", "Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome." ]

[ "Hepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS.\n A prospective, randomized, double-blind, placebo-controlled clinical trial of terlipressin was performed. Subjects with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) or placebo plus albumin in both groups. The dose was doubled on day 4 if the serum creatinine (SCr) level did not decrease by 30% of baseline. Treatment was continued to day 14 unless treatment success, death, dialysis, or transplantation occurred. Treatment success was defined by a decrease in SCr level to </=1.5 mg/dL for at least 48 hours by day 14 without dialysis, death, or relapse of HRS type 1.\n Fifty-six subjects were randomized to each arm. Treatment success with terlipressin was double that with placebo (25% vs 12.5%, P = .093). SCr level improved from baseline to day 14 on terlipressin (-0.7 mg/dL) as compared with placebo (0 mg/dL), P < .009. Terlipressin was superior to placebo for HRS reversal (34% vs 13%, P = .008), defined by decrease in SCr level </=1.5 mg/dL. Overall and transplantation-free survival was similar between study groups; HRS reversal significantly improved survival at day 180. One nonfatal myocardial infarction occurred with terlipressin, but the total adverse event rate was similar to placebo.\n Terlipressin is an effective treatment to improve renal function in HRS type 1.", "Hepatorenal syndrome (HRS) occurs in about 18% of cirrhotic patients with ascites and is characterized by intense renal vasoconstriction, low glomerular filtration rate and preserved tubular function and normal renal histology. The aim of the present study was to examine the effects of terlipressin on renal function, systemic hemodynamics and clinical outcome in patients with HRS.\n The study was a randomized controlled single-blind trial. We randomly assigned 24 consecutive patients with HRS to treatment with terlipressin 1 mg i.v. at 12-h intervals (group A; n = 12) or placebo at 12-h intervals (group B; n = 12). The end-point of the study was improvement in renal functions defined as reversal of HRS and survival at 15 days.\n The two groups were comparable at baseline. After treatment with terlipressin, urine output significantly (P < 0.05) increased progressively in group A (day 4, 960 +/- 40 mL/24 h; day 8, 1068 +/- 56 mL/24 h) compared with group B (day 4, 451 +/- 40 mL/24 h; day 8, 291 +/- 45 mL/24 h). Creatinine clearance improved (P < 0.05) in group A (day 4, 20.2 +/- 2.1 mL/min; day 8, 35 +/- 2.8 mL/min) compared with group B (day 4, 11.3 +/- 1.3 mL/min; day 8, 9.3 +/- 1.7 mL/min). Serum creatinine decreased in group A but not in group B (day 8, 1.6 +/- 0.01 compared with 3.9 +/- 0.26, P < 0.05). Mean arterial pressure increased significantly (P < 0.05) in group A. Terlipressin administration was associated with transient self-limiting side-effects including crampy abdominal pain in two patients and cardiac arrhythmias in three patients. Five of the 12 patients survived in group A compared with none in group B at day 15 (P < 0.05) and all survivors had reversal of HRS.\n In patients with HRS, terlipressin significantly improved renal functions and systemic hemodynamics, and showed a trend towards better clinical outcome. The drug merits further evaluation with different dosages and longer schedules.", "A treatment to induce a sustained increase in glomerular filtration rate in patients with hepatorenal syndrome has not yet been identified. Thus, the aim of the present study was to investigate the effects of terlipressin for 2 days on the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome.\n A double-blind, cross-over randomized study was performed in nine patients. Patients received terlipressin (2 mg/day for 2 days) and a placebo for 2 days in a randomized order.\n Terlipressin administration significantly increased creatinine clearance (from 15+/-2 ml/min to 27+/-4 ml/min) and urine output (from 628+/-67 ml/day to 811+/-76 ml/day), but did not significantly change urinary sodium concentrations. Urinary sodium excretion was not significantly different after placebo administration (0.6+/-0.1 mmol/24 h) and terlipressin administration (9.3+/-7.2 mmol/24 h). Terlipressin administration significantly decreased plasma concentrations of renin and aldosterone but not atrial natriuretic peptide levels. Placebo elicited no significant effects.\n This study shows that 2-day terlipressin administration increases the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome.", "Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome.\n Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months.\n Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases.\n As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.", "Hepatorenal syndrome (HRS) is a pre-renal-like dysfunction that generally onsets in cirrhotic patients presenting ascites. We investigated the improvement of renal function in subjects with hepatorenal syndrome after terlipressin administration and the survival times after this treatment. Fifty-two patients affected by cirrhosis, with diagnosis of hepatorenal syndrome were treated with intravenous terlipressin plus albumin (group A) or with albumin alone (group B). Liver and renal function, plasma renin activity, and aldosterone plasma levels were monitored.\n Patients from group A showed a significant improvement (p < 0.001) of renal function valued by creatinine rate compared with the results obtained in group B. The probability of survival was higher in the group A (p < 0.0001).\n Our results seem to confirm that the administration of terlipressin plus albumin improves renal function in patients with cirrhosis and type I HRS and that a reversal of hepatorenal syndrome is strongly associated with improved survival." ]

[ "10802796", "11673585" ]

[ "Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study.", "Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy." ]

[ "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.", "Animal and human studies suggest that beta(2)-adrenergic agonists exert anabolic effects on muscles, inducing and preventing atrophy after a variety of insults. Based on data from an open-label trial of albuterol in 15 patients with facioscapulohumeral dystrophy (FSHD), the authors conducted a randomized, double-blind, placebo-controlled trial of sustained-release albuterol in this disease.\n Ninety patients were randomized to three groups: placebo; 8.0 mg albuterol twice daily; or 16.0 mg albuterol twice daily. Patients were treated for 1 year with assessments at baseline and weeks 13, 26, and 52. The primary outcome was the 52-week change in global strength by maximum voluntary isometric contraction testing (MVICT). Secondary outcomes included changes at 52 weeks in strength by manual muscle testing (MMT), grip strength, functional testing, and muscle mass assessed by dual energy x-ray absorptiometry (DEXA).\n Eighty-four patients completed the study. The mean changes in composite MVICT scores were not significantly different between the groups (mean +/- SD: placebo 0.20 +/- 0.91; low dose -0.04 +/- 0.84; high dose 0.08 +/- 0.98). Similarly, there were no differences in the mean MMT change (placebo 0.04 +/- 0.16; low dose -0.03 +/- 0.13; high dose 0.00 +/- 0.15). Grip improved in both treatment groups compared to placebo (placebo -0.53 +/- 4.13, low dose +1.90 +/- 3.34 [p = 0.02], high dose +1.70 +/- 4.13 [p = 0.03]). The high-dose group had a significant increase in lean mass by DEXA (+1.57 +/- 1.71 kg) compared to placebo (0.25 +/- 2.24; p = 0.007). Albuterol was well tolerated; side effects included cramps, tremors, insomnia, and nervousness.\n Although albuterol did not improve global strength or function in patients with FSHD, it did increase muscle mass and improve some measures of strength." ]

[ "14750575", "14750576", "16715687" ]

[ "The prognostic importance of detecting mild sensory impairment in leprosy: a randomized controlled trial (TRIPOD 2).", "Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomized controlled trial (TRIPOD 3).", "Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy." ]

[ "This study was designed to investigate whether leprosy patients diagnosed with mild sensory impairment have a better prognosis when treated with steroids than similarly impaired patients treated with placebo. A multi-centre, randomized, double-blind, placebo-controlled trial was conducted in Nepal and Bangladesh. Patients were eligible if they had a confirmed leprosy diagnosis, were between 15 and 50 years old, had mild sensory impairment of the ulnar or posterior tibial nerve of less than 6 months duration and did not require steroids for other reasons. 'Mild impairment' was defined as 'impaired on the Semmes-Weinstein monofilament test, but testing normal on the ballpen sensory test'. Subjects were randomized to either prednisolone treatment starting at 40 mg per day, tapering over 4 months, or placebo. Nerve function was monitored monthly. Any patient who deteriorated was taken out of the trial and was put on full-dose steroid treatment. Outcome assessment was done at 4, 6, 9 and 12 months from the start of the treatment. Outcome measures were the proportion of patients needing full-dose prednisolone and the Semmes-Weinstein sum scores. Each patient contributed only one nerve to the analysis. Seventy-five patients had nerves eligible for analysis, of whom 41 (55%) and 34 (45%) were allocated to the prednisolone and placebo arms, respectively. At 4 months, three patients in the prednisolone arm (7%) and six in the placebo arm (18%) had an outcome event requiring full dose steroids. At 12 months, these proportions had almost reversed, 11 (27%) and 6 (18%) in the treatment and placebo arms, respectively. In the latter group, 75% had recovered spontaneously after 12 months. Prednisolone treatment of sensory impairment of the ulnar and posterior tibial nerves detectable with the monofilament test, but not with the ballpen test, did not improve the long-term outcome in terms of recovery of touch sensibility, not did it reduce the risk of leprosy reactions or nerve function impairment beyond the initial 4-month treatment phase. Two unexpected main findings were the strong tendency of mild sensory impairment to recover spontaneously and the fact that patients with mild sensory impairment without any other signs or symptoms of reaction or nerve function impairment are relatively rare.", "Some leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT.", "The objective of this randomized trial was to compare three different steroid regimens in treating type 1 reactions in leprosy in routine clinical practice.\n The study design was a multicentre, double-blind, randomized, controlled, parallel group trial in patients with acute reversal reactions. The trial was conducted in six leprosy treatment centres in India. A total of 334 participants with acute type 1 reaction were recruited to the trial and randomized to one of three prednisolone regimens: high dose (60 mg per day) or low dose (30 mg per day) both tapered over 20 weeks, and short duration (60 mg per day tapered over 12 weeks). The main outcome measure was the proportion of patients failing to respond to treatment and requiring additional steroids.\n At the end of 12 months, 46% on the short course required additional steroids compared with 31% on the low dose and 24% on the high dose regimen.\n The two 20-week regimens were significantly better than the 12-week regimen. The high dose 20-week regimen was marginally and non-significantly better than the low dose regimen, but the high dose regimen contained 50% more steroid. Reactions in leprosy persist over many months and require long courses of steroids." ]

[ "12702127", "15980691", "12830407", "12968087", "12001042", "15647105", "11504984", "20515418" ]

[ "TRIZAL study: switching from successful HAART to Trizivir (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results.", "Antiretroviral treatment simplification with 3 NRTIs or 2 NRTIs plus nevirapine in HIV-1-infected patients treated with successful first-line HAART.", "Outcome of 2 simplification strategies for the treatment of human immunodeficiency virus type 1 infection.", "Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection.", "A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in human immunodeficiency virus infection.", "Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment.", "Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA.", "Abacavir/lamivudine/zidovudine maintenance after standard induction in antiretroviral therapy-naïve patients: FREE randomized trial interim results." ]

[ "To assess the antiviral efficacy, safety, and adherence in subjects who switched to Trizivir following long-term HIV-1 RNA suppression.\n A randomized, open-label, multicentre, 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months, with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening.\n Subjects were randomized 1:1 to continue their current treatment or to switch to a simplified treatment with Trizivir administered twice daily. Assessments included plasma HIV-1 RNA, lymphocyte counts, clinical laboratory evaluations, adverse events, and adherence to treatment (obtained via subject self-report). Treatment failure was defined as a plasma viral load of >/= 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of randomized treatment.\n At week 48, the proportion of treatment failures in Trizivir arm (23/106, 22%) was noninferior to that observed in continued arm (23/103, 22%) with a treatment difference stratified by prior ART of 1.2%[-10.1; 12.5]. Incidence of adverse events was similar in both treatment groups. The incidence of possible hypersensitivity reaction in the Trizivir trade mark arm was 10%. Significant reductions in cholesterol and triglyceride plasma levels were observed in the Trizivir arm (P < 0.001 and P = 0.006, respectively).\n Switching to Trizivir offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy.", "To assess the virologic noninferiority of an antiretroviral treatment simplification with coformulated zidovudine/lamivudine/abacavir (group 1) vs. coformulated zidovudine/lamivudine plus nevirapine (group 2) in HIV-1-infected patients receiving successful first-line highly active antiretroviral therapy.\n This is a prospective, multicenter, open-label, comparative, randomized, noninferiority study. A delta of 15% for differences in virologic suppression <200 copies/mL between groups was prespecified with a 1-sided 0.025 significance level.\n A total of 134 patients were included into this study: 68 were allocated to group 1 and 66 to group 2. By intention-to-treat analysis (switch equals failure), the percentage of virologic suppression <200 copies/mL (<50 copies/mL) at week 48 was 71.0% (65.1%) and 73.0% (63.3%) in groups 1 and 2, respectively (estimate for differences [<200 copies/mL]: -2.1, 95% CI: -17.4-13.1, P=0.783). Thirteen and 14 patients in groups 1 and 2, respectively, discontinued therapy due to adverse events. Dyslipidemia improved in both groups, with a higher improvement in low-density lipoprotein cholesterol (P=0.049) in group 1.\n Group 1 is not inferior to group 2 regarding virologic suppression <200 copies/mL. Both strategies improve lipid profile.", "In a prospective, open-label, 104-week study, patients who were infected with human immunodeficiency virus type 1 (virus load, <50 copies/mL) and who were receiving protease inhibitor-based therapy were randomly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz. Treatment failure, defined as virological failure (virus load, >500 copies/microL) or any clinical or biochemical adverse event with a grade of >or=3 (on the basis of the World Health Organization [WHO] or American Heart Association [AHA] scales), was the primary outcome measurement. Failure rates were more frequent in the group treated with protease inhibitors (P<.01), and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir. Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors. Fewer patients who received efavirenz experienced viral rebound. Among all groups, the mean increase in the CD4 cell count was 131 cells/microL (P<.001), with no significant difference between groups. This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients.", "We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved.\n We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter.\n At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups.\n When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.\n Copyright 2003 Massachusetts Medical Society", "This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens (n=79) or a change to the simplified regimen of abacavir-lamivudine-zidovudine (n=84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1) RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation. After a median follow-up of 84 weeks, virologic failure was 6% in the continuation and 15% in the simplified group (P=.081). Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure. Study treatment was discontinued because of adverse events in 20% of the continuation and 7% of the simplified group (P=.021). Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels; however, this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen.", "Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects.\n An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors.\n At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments.\n In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.", "To assess the antiviral efficacy, safety and adherence in patients switched to an abacavir-containing nucleoside reverse transcriptase inhibitor (NRTI) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease inhibitor (PI) combination.\n In an open-label, multicentre study, patients receiving 2NRTI plus PI for at least 6 months, with a history of undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1 RNA < 50 copies/ml at screening, were randomly assigned to replace the PI with abacavir (n = 105) or continue the same treatment (n = 106). Clinical assessments included plasma HIV-1 RNA, chemistry, haematology, lymphocyte counts, and adverse event reports. Adherence to treatment was assessed by patient self-report.\n A significantly longer time to treatment failure was demonstrated in the abacavir arm compared with the PI arm (P = 0.03) while treatment failure was experienced by significantly more patients in the PI arm: 24 (23%) versus 12 (12%) (P = 0.03). Therapy-limiting toxicity led to treatment failure in eight versus 14 cases in the abacavir and PI arms, respectively, whereas virological rebound was the cause in four versus two cases. Significant reductions in cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed in the abacavir arm (P < 0.001 andP = 0.035, respectively). The number of patients reporting no difficulty in taking their therapy showed a marked increase from baseline in the abacavir arm.\n The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.", "Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 <or=350 cells/mm(3) and HIV-1 RNA concentrations (viral load [VL]) greater than 30,000 copies per milliliter. Patients were randomized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination. Eligible subjects switched to abacavir/lamivudine/zidovudine (TZV) or continued the PI-containing regimen. Here we present the 48-week data with virologic success rate (failure: VL > 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period." ]

[ "7880187", "10531077", "11777359", "11285377", "7788149", "15760929", "15194574", "13275875" ]

[ "Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment.", "A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects.", "Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial.", "The relationship between soft tissue swelling, joint space narrowing and erosive damage in hand X-rays of patients with rheumatoid arthritis.", "Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial.", "A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs.", "Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial.", "EMPIRE Rheumatism Council; multi-centre controlled trial comparing cortisone acetate and acetyl salicylic acid in the long-term treatment of rheumatoid arthritis; results up to one year." ]

[ "Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population.\n Patients with active RA diagnosed at age > or = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years.\n During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group.\n Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.", "To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis.\n One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation.\n The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm.\n This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.", "Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis.\n To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis.\n 2-year randomized, double-blind, placebo-controlled clinical trial.\n 2 outpatient rheumatology clinics.\n 81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs.\n 41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication.\n Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months.\n In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group.\n Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.", "To test the hypotheses that the progression of joint space narrowing behaves differently from the progression of erosions and that clinically and radiologically assessed soft tissue swelling relates more to diffuse cartilage loss than to erosive damage.\n Radiographs and clinical data were obtained from 28 patients in a prospective, multicentre, randomized, placebo-controlled trial of prednisolone 7.5 mg daily over 2 yr. Radiographic scoring included the Larsen score, joint space narrowing and soft tissue swelling. Clinical joint inflammation in the hands was assessed every 3 months and cumulative synovitis score over the period of study was then calculated for each joint. The placebo-treated patients and the prednisolone-treated patients were analysed separately. The Larsen scores were compared after log transformation [transformed score=log(10) (original score+1)]. Changes in Larsen scores and joint space narrowing scores were compared with the cumulative presence of clinical synovitis and radiological soft tissue swelling using the correlation coefficient.\n There was a difference in the rate of progression in the Larsen score between placebo- and prednisolone-treated patients, but there was no significant difference in the rate of joint space loss. In placebo-treated patients, measures of synovitis correlated more strongly with progression of joint space narrowing than with changes in the Larsen score. In prednisolone-treated patients there was no correlation between clinical synovitis and change in Larsen score (r=0.029) and only a slight and non-significant correlation with joint space narrowing (r=0.127). Radiographic evidence of soft tissue swelling remained correlated with joint space narrowing (r=0.279, P:<0.001) but was not correlated with change in Larsen score (r=-0.113, P:<0.001 for difference between correlations). The correlation between Larsen score progression and joint space narrowing seen in the non-treated patients was completely abolished in the glucocorticoid-treated group (r=-0.003).\n The progression of joint space narrowing behaves differently from the progression of erosions. Prednisolone slows (or even stops) the progression of erosions (as assessed by the Larsen score) while making no difference to the progression of cartilage loss (as assessed by joint space narrowing). The results also suggest that synovitis, whether measured clinically or radiologically, is more closely related to diffuse cartilage loss than to erosion progression. Any link between synovitis and erosions is abolished by glucocorticoid therapy while the link between synovitis and cartilage loss is not, pointing to at least two different mechanisms for these observed radiological features.", "The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis (RA) was studied. Forty patients starting aurothioglucose were randomized to receive either prednisone or placebo for 18 weeks. The dose was 10 mg/day in the first 12 weeks, 7.5 mg/day in weeks 13 and 14, 5 mg/day in weeks 15 and 16, and 2.5 mg/day in weeks 17 and 18. Patients were followed for 44 weeks. We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12. Response to prednisone was noticed in 60% of the patients. After tapering prednisone, a rebound deterioration was noticed at weeks 20 and 24 in 58% of the responders. No significant differences in X-ray progression were found between the two groups. We concluded that oral prednisone (10 mg/day) significantly reduces short-term disease activity in 60% of patients with active RA. The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended.", "In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed.\n To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs.\n In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry.\n 291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients.\n IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.", "Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory. Studies showing radiological benefit suggest that continued treatment is required to sustain the effect.\n To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years.\n Double blind placebo controlled trial.\n Patients with rheumatoid arthritis, duration <3 years (n = 167), were started on a disease modifying antirheumatic drug (DMARD; sulphasalazine) and allocated by stratified randomisation to prednisolone 7 mg/day or placebo. Primary outcome measure was radiological damage, assessed by the modified Sharp method. Clinical benefit was a secondary outcome. A proactive approach to identifying and treating corticosteroid adverse events was adopted. Patients who discontinued sulphasalazine were offered an alternative DMARD.\n 90 of 257 patients eligible for the study refused to participate (more women than men). Of those enrolled, 84% were seropositive for rheumatoid factor, median age 56 years, median disease duration 12 months, female to male ratio 1.8:1. Prednisolone was given to 84 patients; of these 73% continued prednisolone and 70% sulphasalazine at 2 years. Of the 83 patients on placebo, 80% continued placebo and 64% sulphasalazine at 2 years. There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years.\n Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years. Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs.", "nan" ]

[ "8362533", "12222925", "8109113", "7974754", "9448615", "1461854" ]

[ "Pulmonary function after cholecystectomy performed through Kocher's incision, a mini-incision, and laparoscopy.", "Comparison of postoperative pulmonary function tests after cholecystectomy performed through Kocher's incision and mini-incision.", "Minicholecystectomy vs conventional cholecystectomy: a prospective randomized trial--implications in the laparoscopic era.", "Mini-lap cholecystectomy--an attractive alternative to conventional cholecystectomy.", "Randomized clinical trial of conventional cholecystectomy versus minicholecystectomy.", "Patient recovery following cholecystectomy through a 6 cm or 15 cm transverse subcostal incision: a prospective randomized clinical trial." ]

[ "Comparative pulmonary function after cholecystectomy performed through Kocher's incision, a mini-incision, and laparoscopy was evaluated. Forty-five patients were randomly and prospectively divided into three groups of 15 each, depending on the surgical access employed. Forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and forced expiratory flow at 25% to 75% (FEF25-75%) were determined 1 to 3 days before and 16 to 24 hours after cholecystectomy. The percent reduction of FVC (p = 0.0170), FEV1 (p = 0.0191), and FEF25-75% (p = 0.0045) was smaller after laparoscopic cholecystectomy than after Kocher's incision cholecystectomy. The percent reduction of FVC (p = 0.0170) was smaller after mini-incision cholecystectomy than after Kocher's incision cholecystectomy. There was no difference in the FEV1 (p = 0.0971) or FEF25-75% (p = 0.2058) between these two groups. FEF25-75% was significantly less impaired in the laparoscopic group than in the mini-incision group (p = 0.0327). No difference between these two groups was found in FVC (p = 0.5755) or FEV1 (p = 0.3952). It is concluded that postoperative pulmonary function is less impaired after laparoscopic cholecystectomy than after either mini-incision or Kocher's incision cholecystectomy.", "Comparative pulmonary function after cholecystectomy performed through Kocher's incision and mini-incision were evaluated. One hundred patients were included and systematically divided into two groups of 50 each. The first group underwent conventional cholecystectomy and the second group underwent mini-cholecystectomy. Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and peak expiratory flow rate (PEFR) were determined on the preoperative day and on postoperative days 1, 2, and 3. The percentage of reduction of VC on postoperative day 1 (P < 0.01), 2 (P < 0.01), and 3 (P < 0.01) after Kocher's incision was more than the percentage of reduction after mini-incisions on the corresponding day, respectively (P < 0.01, P < 0.01, and P < 0.01). The percentage of reduction of FVC (P = 0.0001, 0.0001, and 0.0001) was lesser after mini-incision cholecystectomy than after Kocher's incision cholecystectomy on the three corresponding postoperative days. The percentage of reduction of FEV1 after mini-incision was lesser than after Kocher's incision cholecystectomy on the three corresponding postoperative days (P = 0.001, 0.000, and 0.000). There was no significant difference in PEFR between the two groups on the three corresponding postoperative days (P = 0.731, 0.652, and 0.393). It is observed that min-incision cholecystectomy is followed by superior postoperative pulmonary function to that seen after Kocher's incision.", "The objective of this study was to compare results of elective \"open\" conventional cholecystectomy (CC) to those of minicholecystectomy (MC). A clinical prospective, randomized trial was designed. The setting was an academic general surgical unit. In the CC group were 26 patients; in the MC group were 24 patients. In the CC group a conventional open cholecystectomy was performed through a subcostal incision; in the MC group operation through an initial 5-cm subcostal incision was done. Mean length of wound was 14.4 cm and 5.4 cm in the two groups, respectively (p < 0.001). Mean operative time was 60 and 59 minutes, respectively. Mean operative difficulty, estimated on a 1-10 scale, was 3.4 and 5.6, respectively (p < 0.05). Mean postoperative analgesia requirements (number of doses of 10 mg morphine sulphate) were 5.8 and 4.0, respectively (p = 0.002). Mean duration of hospitalization was 4.7 and 3.0 days, respectively (p < 0.001). Mean \"overall patient satisfaction,\" estimated on 1-10 scale, was 6 and 8.3, respectively (p = 0.002). We conclude that Minicholecystectomy offers less pain, earlier recovery, and better cosmetic results than the conventional \"open\" procedure. Published results of MC compare favorably with those of laparoscopic procedures. The implications of these results in the \"laparoscopic era\" are discussed.", "A prospective study was conducted to determine the safety and efficacy of cholecystectomy through a 5 cm transverse abdominal incision. 181 consecutive patients who underwent elective cholecystectomy for symptomatic gall stone disease in a single surgical unit at the All India Institute of Medical Sciences, New Delhi between December 1990 to February 1992, were prospectively randomized into 5 cm transverse and midline incision groups. Operative time, blood loss, post-operative stay and complications were compared in the two groups. Ninety seven patients were included in the transverse incision group and 84 patients in the midline group. Cholecystectomy could be safely performed through a 5 cm transverse incision in 84 patients (86.8%) without increase in operative complications, morbidity or mortality. In another 84 patients cholecystectomy was performed through a midline incision. The average operating time and blood loss were comparable in both groups. The average post-operative stay in 5 cm transverse incision group was 2.6 days (range 1-4 days) and in the midline group was 4.0 days (range 3-5 days). There were 7 post-operative complications (all wound infections) in the 5 cm transverse group and 12 post-operative complications (10 wound infections and 2 pneumonitis) in the midline group. However, the difference in wound infection rate was not statistically significant (p > 0.1). In Conclusion, Cholecystectomy can be safely performed through a 5 cm transverse incision.", "The main argument for laparoscopic cholecystectomy in preference to open cholecystectomy appears to be based on less traumatic incisions inflicted on the abdominal wall. To investigate the effects of different incision lengths on patients following elective open cholecystectomy, a randomized clinical study was conducted.\n In this study 130 patients were randomly assigned to undergo either open cholecystectomy through a transverse subcostal incision of mean length 5.8 cm, so called minicholecystectomy (65 patients), or to undergo conventional cholecystectomy through a paracostal incision of mean length 13.1 cm (65 patients). The perception of pain after operation was measured by a visual analogue scale. To register late complications the mean(s.d.) hospitalization period after operation was extended to 11.5(1.2) days in the minicholecystectomy group and 15.4(2.5) days in the conventional cholecystectomy group.\n The perceived pain and analgesic requirements were found to be similar in both groups. Twelve of 65 patients in the minicholecystectomy group and four of 65 in the conventional cholecystectomy group developed wound haematoma.\n On the basis of this prospective randomized study, the hypothesis that a smaller incision length on the abdominal wall could lower the level of perceived pain, and therefore decrease the postoperative analgesic intake after minicholecystectomy, could not be confirmed.", "The effect of incision length on patient recovery following cholecystectomy has not been investigated previously. In this study, 30 patients with symptomatic gallstones were randomized to cholecystectomy through a 6 cm or 15 cm transverse subcostal incision. Postoperative hospital stay was significantly shorter in the 6 cm incision group (median 3 days vs 5 days; P = 0.0069 Mann-Whitney U-test). In the 6 cm group analgesic requirements were reduced (median 2.5 vs 4.5 intramuscular opiate injections per patient) and recovery of depressed postoperative pulmonary function (FVC and FEV1) was faster (3% difference between groups on day 1 and 7% on day 3), although these differences did not achieve statistical significance. These results suggest that the length of incision may influence patient recovery following elective cholecystectomy. This has important implications as surgery carried out through shorter and less traumatic incisions may offer a cost-effective alternative to laparoscopic cholecystectomy. Moreover, some surgeons may find mini-laparotomy cholecystectomy easier to adopt than laparoscopic techniques." ]

[ "19230757", "19489063", "10686463", "15042543", "18280205" ]

[ "Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study.", "A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome.", "A randomized, double-blind placebo-controlled trial of iron in restless legs syndrome.", "A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome.", "A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome." ]

[ "Restless Legs Syndrome (RLS) is a primary disorder of sensation that affects sleep and has been associated with iron deficiency. The purpose of this study was to determine if symptomatic RLS patients with low-normal serum ferritin levels benefit from oral iron replacement.\n This was a randomized, placebo-controlled, double-blinded study. Eligible patients were randomized to oral iron therapy vs. appearance-matched placebo and followed over a 12 week period.\n Baseline International Restless Leg Scale (IRLS) scores for the treatment (24.8+/-5.72) and placebo (23.0+/-5.03) groups were similar. Baseline ferritin levels for the treatment (40.6+/-15.3ng/ml) and placebo (36.7+/-20.8ng/ml) groups were also similar. After 12 weeks, IRLS scores decreased more in the treatment arm (10.3+/-7.40) than in the placebo arm (1.14+/-5.64), (p=0.01). Ferritin levels increased more in the treatment arm (25.1+/-20.3ng/ml) than in the placebo arm (7.5+/-13.7ng/ml), (p=0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, (p=0.07).\n This is the first double-blinded, placebo-controlled study to demonstrate statistically significant improvement in RLS symptoms using oral iron therapy in patients with low-normal ferritin. The findings from this study suggest that additional larger randomized placebo-controlled trials of iron as treatment for patients with low-normal ferritin are warranted.", "Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome (RLS). We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit. Sixty patients with primary RLS (seven males, age 46 (9) years, S-ferritin < or =45 microg/L) recruited from a cohort of 231 patients were randomly assigned in a 12-months double-blind, multi-centre study of iron sucrose 1000 mg (n = 29) or saline (n = 31). The primary efficacy variable was the RLS severity scale (IRLS) score at week 11. Median IRLS score decreased from 24 to 7 (week 11) after iron sucrose and from 26 to 17 after placebo (P = 0.123, N.S. for between treatment comparison). The corresponding scores at week 7 were 12 and 20 in the two groups (P = 0.017). Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose (Kaplan-Meier estimate, log rank test P = 0.0006) suggesting an iron induced superior long term RLS symptom control. Iron sucrose was well tolerated. This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase (7 weeks) and during long-term follow up in patients with variable degree of iron deficiency. Further studies on target patient groups, dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS.\n Copyright 2009 Movement Disorder Society.", "Previous open-label trials have shown iron to be efficacious in the treatment of restless legs syndrome. We performed a randomized, double-blind, placebo-controlled trial of iron sulfate.\n Twenty-eight patients were randomized to receive either ferrous sulfate 325 mg b.i.d. or placebo for 12 weeks. The primary outcome measure was the dichotomous variable of improvement or no improvement in average quality of sleep as recorded by a visual analog scale nightly over a 2-week period, comparing a pretreatment 2-week baseline to weeks 13-14. Secondary outcome measures included a comparison of the quality of sleep as measured by a visual analog scale, effect of restless legs syndrome on life as a whole as measured by a different visual analog scale, and the percentage of nights patients were symptomatic.\n No significant differences were noted between iron and placebo groups for both primary and secondary outcome measures. Responders taking iron did have a significant increase in their iron saturation compared to nonresponders taking iron.\n Iron sulfate does not appear to be an effective empiric treatment for restless legs syndrome.\n Copyright 2000 S. Karger AG, Basel.", "Restless legs syndrome (RLS) is a common disorder in patients with end-stage renal disease (ESRD) that causes motor agitation and insomnia. Because RLS has been associated with iron deficiency, we sought to investigate the effects of intravenous (IV) iron dextran on symptoms of RLS in a double-blind placebo-controlled trial.\n Patients determined to have RLS by International RLS Study Group criteria were administered either iron dextran, 1,000 mg, or normal saline IV in a blinded fashion. Patient demographic data were collected, and blood chemistry tests, liver function studies, serum iron levels, ferritin levels, and total iron-binding capacity were obtained at baseline and 1, 2, and 4 weeks postinfusion. Side effects or adverse events to interventions were monitored, and RLS symptoms were assessed by a rating scale at the same intervals.\n Eleven patients were randomly assigned to the administration of iron dextran, and 14 patients to the administration of saline. RLS severity scores were slightly higher in the placebo group at baseline, but hemoglobin levels, iron stores, and other biochemical parameters did not differ. Although no change in symptoms were seen in the placebo-treated group, significant improvement in RLS symptom scores in response to iron dextran was seen 1 week after infusion (-2; interquartile range [IQR], -6 to -1; P = 0.03, Wilcoxon's rank sums), but was greatest at 2 weeks (-3; IQR, -5 to -2 compared with -1 to 0; P = 0.01). Salutary effects of iron persisted at 4 weeks, but were no longer statistically significant. The significant increase in serum ferritin levels and iron saturation observed in the iron dextran-treated group was not seen in the placebo-treated group. No differences in adverse events were noted between groups.\n High-dose iron dextran infusion is associated with a significant, but transient, reduction in symptoms of RLS in patients with ESRD.", "The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS.\n The study was a randomized, parallel-group double-blind study of 1000mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra.\n At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and a decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinically significant benefit.\n High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies." ]

[ "6351332", "6474386", "3287726", "6364442", "7992443", "8511730" ]

[ "Effect of negative ionisation of inspired air on the response of asthmatic children to exercise and inhaled histamine.", "Effect of positive ionisation of inspired air on the response of asthmatic children to exercise.", "[Ion generator and asthmatic bronchitis/bronchial asthma. Evaluation of an ion generator in the treatment of recurrent asthmatic bronchitis and bronchial asthma].", "Ionisers in the management of bronchial asthma.", "[Ion generators and bronchial asthma. A double-blind placebo controlled study].", "Double blind trial of ionisers in children with asthma sensitive to the house dust mite." ]

[ "To evaluate the effect of negative ionisation of inspired air on bronchial reactivity, 11 asthmatic children were challenged twice by exercise and 10 were challenged twice by histamine inhalation. The children breathed negatively ionised air (4 X 10(5) - 10 X 10(5) ions/cm3) or control room air in random order in a double-blind fashion. All challenges were matched in terms of basal lung function and the exercise tests were matched in terms of ventilation and respiratory heat loss. Exercise-induced asthma was significantly attenuated by exposure to negatively ionised air, the mean postexercise fall in one-second forced expiratory volume (FEV1) being 29% (SE 5%) of the initial value after the control and 21% (3%) after the ionised air test (p less than 0.02). Ten of the 11 subjects developed less exercise-induced asthma while breathing ionised air. Although the median dose of histamine (cumulative breath units) which caused a constant fall in FEV1 for each individual was higher with the ionised air challenge than with the control challenge the difference was not significant. Five of the 10 subjects were less sensitive to histamine and the other five more sensitive when breathing ionised air. It is concluded that negative ionisation of inspired air can modulate the bronchial response to exercise but the effect on the response to histamine is much more variable.", "To evaluate the effect of positive ionisation of inspired air on bronchial reactivity, 12 asthmatic children were twice challenged by exercise in random order. During one test positively ionised air (5-10 X 10(5) ions/cm) was breathed. All challenges were matched in terms of basal lung function and exercise tests were matched in terms of ventilation and respiratory heat loss. Exercise induced asthma was significantly aggravated by exposure to positively ionised air, the postexercise fall in FEV1 (delta FEV1) being 24.7% (SEM and 5.3%) and 35.3% (5%) after the control and ionised air tests respectively (p less than 0.04). It is concluded that positive ionisation aggravates the bronchial response to exercise.", "nan", "Because of recent interest in the possible benefits to asthmatic patients of negative ion generators and the largely uncontrolled and inconclusive nature of earlier studies a double blind crossover study of this treatment was carried out in 20 subjects with stable asthma over six months. After an initial two week period without an ioniser, active or placebo ionisers were installed in subjects' bedrooms for two eight week periods separated by a four week \"washout\" period when no ioniser was present. The study was completed by a final four week period when no ioniser was present. Subjects were randomly allocated to receive an active or a placebo ioniser first. Subjects recorded their peak expiratory flow rate (PEFR) twice daily, completed a daily symptom score questionnaire, and noted any treatment they took on a diary card. Recordings were completed throughout the trial. Ion counts and dust concentrations were measured in subjects' bedrooms during the study. Mean ion counts rose considerably when ionisers were activated (p less than 0.001). There were no significant differences in PEFR, symptom score, or consumption of medication between the periods that active ionisers and either no ionisers or placebo ionisers were in operation. This study has failed to show a statistically significant benefit in asthmatic subjects from the use of negative ion generators.", "In this double blind, placebo-controlled study we examined the value of using a device for ionizing the air in the immediate environment as a therapy for asthma bronchiale. Nineteen adult patients with stable, reversible asthma were randomised to blind treatment with either an active device or an inactive placebo-device. After four weeks treatment the patients were given the alternative device for another period of four weeks. We measured daily peak-flow, symptomscore, use of medicine and spirometry and found no differences between the two periods. Therapy with ionization of the environmental air in patients with bronchial asthma should not be recommended.", "Manufacturers of ionisers claim many benefits from the use of their devices, including the relief of asthma. Particles removed from the air are likely to include airborne allergens, so ionisers may achieve an effect by reducing the allergen load.\n The effect of ionisers on airborne concentrations of house dust mite allergen Der p I was investigated in a double blind, crossover, placebo controlled trial in the homes of 20 children with allergic asthma. Subjects recorded their peak expiratory flow rate (PEFR) twice daily and completed a daily symptom score and treatment schedule on a diary card for two six week periods, one with an active ioniser and the other with a placed ioniser (randomly allocated) used in the living room and the bedroom.\n Airborne Der p I concentrations fell significantly during the active period compared with the placebo period, but there was no significant change in PEFR, symptom scores, or treatment usage. There was an increase in night time cough which almost reached significance during the active period.\n This study indicates that the use of ionisers cannot be recommended in the homes of asthmatic subjects to improve their symptoms. The significant reduction of airborne allergen concentrations may be of use as part of a multidevice allergen avoidance regimen, but the increase in night time cough requires further study." ]

[ "9417009", "8340985", "9110906" ]

[ "Comparison of ring block, dorsal penile nerve block, and topical anesthesia for neonatal circumcision: a randomized controlled trial.", "Topical anesthesia during circumcision in newborn infants.", "Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision." ]

[ "Beliefs about the safety and effectiveness of current anesthetics have resulted in many newborns being circumcised without the benefit of anesthesia.\n To compare ring block, dorsal penile nerve block, a topical eutectic mixture of local anesthetics (EMLA), and topical placebo when used for neonatal circumcision. The placebo represented current practice, with no anesthetic for neonatal circumcision.\n A randomized controlled trial.\n Antenatal units in 2 tertiary care hospitals in Edmonton, Alberta.\n A consecutive sample of 52 healthy, full-term, male newborns, aged 1 to 3 days.\n Physiological and behavioral monitoring occurred in a series of trials: baseline, drug application, preparation, circumcision, and postcircumcision. Surgical procedures defined the following 4 stages of the circumcision: cleansing, separation, clamp on, and clamp off. Methemoglobin level was assessed 6 hours after surgery.\n Heart rate, cry, and methemoglobin level.\n Newborns in the untreated placebo group exhibited homogeneous responses that consisted of sustained elevation of heart rate and high-pitched cry throughout the circumcision and following. Two newborns in the placebo group became ill following circumcision (choking and apnea). The 3 treatment groups all had significantly less crying and lower heart rates during and following circumcision compared with the untreated group. The ring block was equally effective through all stages of the circumcision, whereas the dorsal penile nerve block and EMLA were not effective during foreskin separation and incision. Methemoglobin levels were highest in the EMLA group, although no newborn required treatment.\n The most effective anesthetic is the ring block; EMLA is the least effective. It is our recommendation that an anesthetic should be administered to newborns prior to undergoing circumcision.", "To determine the efficacy of topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain from neonatal circumcision.\n Randomized, controlled trial.\n Normal newborn nursery in a university teaching hospital.\n Twenty-seven newborn, full-term male neonates, aged 1 to 3 days.\n Heart rate, transcutaneous oxygen saturation, facial activity, and crying.\n Compared with baseline, all newborns experienced pain as evidenced by increased heart rate of an average of 40 beats per minute (F [8, 25] = 14.12; P < .0001), decreased oxygen saturation of 3% (F [8, 25] = 15.02; P < .0001), and more facial actions indicative of pain (F [8, 25] = 5.25; P < .002) during all phases of the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by lower heart rate of an average of 25 beats per minute (F [1, 25] = 14.92; P < .001), higher oxygen saturation of 5%, particularly during the clamping and lysis phases (F [1, 25] = 19.83; P < .0001), 20% less facial activity (F [1, 25] = 12.01; P < .002), and 15% less crying during the clamping, Gomco clamp application, and incision of the foreskin. There were no differences between groups in the spectral crying parameters.\n Circumcision procedure produces pain responses that EMLA diminishes. Thus, EMLA may be a useful agent for pain management in neonatal circumcision.", "Neonatal circumcision is a painful surgical procedure often performed without analgesia. We assessed the efficacy and safety of 5 percent lidocaine-prilocaine cream (Emla) in neonates undergoing circumcision.\n We carried out a double-blind, randomized, controlled trial in 68 full-term male neonates: 38 were assigned to receive lidocaine-prilocaine cream, and 30 to receive placebo. One gram of lidocaine-prilocaine or placebo cream was applied to the penis under an occlusive dressing for 60 to 80 minutes before circumcision. Behavioral (facial activity and time spent crying) and physiologic (heart rate and blood pressure) responses were recorded during the procedure. Blood samples were obtained at various times after drug application for measurements of methemoglobin and plasma lidocaine, prilocaine, and o-toluidine (a metabolite of prilocaine).\n A total of 68 and 59 neonates were included in the safety and efficacy analyses, respectively. Demographic characteristics such as gestational age and birth weight did not differ between the lidocaine-prilocaine and placebo groups. During circumcision, the neonates in the lidocaine-prilocaine group had less facial activity (P= 0.01), spent less time crying (P<0.001), and had smaller increases in heart rate (P=0.007) than the neonates in the placebo group. Facial-activity scores were 12 to 49 percent lower during various steps of the procedure in the lidocaine-prilocaine group. As compared with neonates in the placebo group, infants in the lidocaine-prilocaine group cried less than half as much and had heart-rate increases of 10 beats per minute less. Blood methemoglobin concentrations (expressed as a percentage of the hemoglobin concentration) were similar (1.3 percent) in both groups. Lidocaine and prilocaine were detected in plasma in 23 (61 percent) and 21 (55 percent) of the infants treated with lidocaine-prilocaine cream, respectively.\n Lidocaine-prilocaine cream is efficacious and safe for the prevention of pain from circumcision in neonates." ]

[ "16337461", "11754675", "9207726", "12269647" ]

[ "Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo.", "Comparison of cefuroxime with or without intranasal fluticasone for the treatment of rhinosinusitis. The CAFFS Trial: a randomized controlled trial.", "Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children.", "Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis." ]

[ "Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established.\n To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis.\n In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring.\n Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events.\n In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection.", "It is not known whether intranasal corticosteroids are beneficial to treat acute rhinosinusitis in patients with a history of chronic or recurrent sinus symptoms.\n To assess whether the addition of an intranasal corticosteroid to antibiotic therapy affects the speed and rate of recovery of such patients with acute rhinosinusitis.\n A double-blind, randomized, placebo-controlled multicenter trial of 95 patients (median age, 39 years) with a history of recurrent sinusitis or chronic rhinitis and evidence of acute infection by sinus radiograph or nasal endoscopy, which was conducted from October 1998 through April 2000 at 22 sites (12 primary care and 10 otolaryngology).\n Two puffs (total dose, 200 microgram) of fluticasone propionate (n = 47) or placebo nasal spray (n = 48) in each nostril once daily for 21 days; all received 2 puffs of xylometazoline hydrochloride in each nostril twice daily for 3 days and 250 mg of cefuroxime axetil twice daily for 10 days.\n Time to clinical success (patient reported cured or much improved) during telephone follow-up at 10, 21, and 56 days.\n A total of 88 patients (93%) completed follow-up. Patients recorded their symptoms, work assessment, and compliance during the 3-week treatment phase. Patients receiving fluticasone achieved a significantly higher rate of clinical success than patients receiving placebo (93.5% vs 73.9%; P =.009). Patients treated with fluticasone improved significantly more rapidly (median of 6.0 days to clinical success) vs patients in the placebo group (median of 9.5 days; P =.01).\n The addition of fluticasone to xylometazoline and antimicrobial therapy with cefuroxime improves clinical success rates and accelerates recovery of patients with a history of chronic rhinitis or recurrent sinusitis who present for treatment of acute rhinosinusitis.", "The role of topical corticosteroids in the treatment of acute sinusitis has not been established in children.\n An attempt was made to determine the impact of topical corticosteroids as an adjunct to antibiotic treatment in the management of childhood sinusitis.\n In a double-blind, placebo-controlled study, 151 children with sinusitis were recruited from a general pediatric outpatient clinic and 89 completed a 3-week trial. Treatment consisted of amoxicillin-clavulanate potassium, 40 mg/kg/d tid, combined with bid nasal spray of either budesonide, 50 micrograms, to each nostril (n = 43) or placebo )n = 46_ for 3 weeks. Patients maintained daily symptom cards throughout the study and were examined by the same physician each week.\n Clinical symptoms and signs decreased significantly in both treatment groups in comparison to baseline (P < .01). We detected a significant improvement in the scores of the cough and nasal discharge at the end of second week in the budesonide group when compared with placebo (P < .05). Friedman nonparametric repeated measures ANOVA test revealed a significant decrease in the total weekly scores of cough during the second week of budesonide treatment (P < .001) in contrast to continuous decline during the second and third weeks in the placebo group (P < .001 and P < .05, respectively). While the nasal discharge score decreased significantly during the second week in the budesonide group (P < .01), no significant effect on the nasal discharge score was observed in the placebo group.\n These data suggest that topical corticosteroids may be a useful ancillary treatment to antibiotics in childhood sinusitis and effective in reducing the cough and nasal discharge earlier in the course of acute sinusitis.", "Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis.\n To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis.\n In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites.\n Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression.\n As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone." ]

[ "2711309", "10486394", "1402964", "2360466", "6339686" ]

[ "Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures.", "Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.", "Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy?", "Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours.", "Phenytoin and postoperative epilepsy. A double-blind study." ]

[ "Phenytoin (15 mg/kg) was administered intravenously to 189 patients shortly before their intracranial, supratentorial surgery was completed. Intravenous phenytoin of 5-6 mg/kg/day in three divided doses was administered daily for the first 3 postoperative days. Therapeutic serum levels (10-20 micrograms/mL) were achieved in 113 (59.8%) patients. An equally constituted, randomized control group of 185 patients received a placebo under identical conditions. The group receiving phenytoin had only one immediate and two early postoperative seizures. The 185 controls had four immediate and nine early postoperative seizures. None of the follow-up computed tomography scans of the patients with seizures showed postoperative hematoma. One patient had a significant tension pneumocranium, a possible cause of postoperative seizures. To avoid a decrease in the serum anticonvulsant level due to intraoperative blood loss, it is suggested that for patients who need an urgent or emergent craniotomy, prophylatic anticonvulsant medication should be given at least 20 minutes before completion of wound closure.", "To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.\n A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.\n Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.\n For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.", "A total of 276 patients with a high risk of developing postoperative seizures were randomised to treatment with carbamazepine or phenytoin for six or 24 months, or to no treatment. No significant differences were found (though the confidence limits were fairly wide) between the regimes in respect of the incidence of seizures or death. In a substantial proportion of the patients postoperative epilepsy remained a continuing disability. A high incidence of drug-related side effects was found in the treatment groups. Prophylactic anticonvulsants cannot therefore be recommended routinely following supratentorial craniotomy.", "One hundred and twenty-eight adult patients presenting with and operated on for supratentorial neoplasms were studied. Sixty-five had preoperative seizures and were treated with antiepileptic drugs (AEDs). Among the 63 patients without preoperative epileptic fits, 41 were given AEDs (either phenobarbital or phenytoin) as prophylactic treatment and 22 were not treated. The preoperative epilepsy course was considered with respect to tumour site and histological type. Early and late postoperative seizure occurrence was considered in the different groups of patients. The results suggest the usefulness of a short term preventive treatment with AEDs after surgery in patients without preoperative seizures. In patients with preoperative epilepsy, AEDs should be continued after surgery. However long-term AEDs treatment should not be recommended in patients without preoperative epilepsy. In fact, no significant difference in late seizure occurrence was found between preventively treated and untreated patients.", "A double-blind trial of phenytoin therapy following craniotomy was performed to test the hypothesis that phenytoin is effective in reducing postoperative epilepsy. A significant reduction in the frequency of epilepsy was observed in the group receiving the active drug up to the 10th postoperative week. Half of the seizures occurred in the first 2 weeks and two-thirds within 1 month of cranial surgery. High rates of epilepsy were observed after surgery in patients with meningioma, metastasis, aneurysm, and head injury. Routine prophylaxis with phenytoin (in a dosage of 5 to 6 mg/kg/day) would seem to be indicated, particularly in high-risk patients and, where possible, this treatment should be started 1 week preoperatively. Seizure control is best when therapeutic levels of phenytoin are maintained." ]

[ "15099656", "12204321", "7174622", "1091161", "9649975", "6342564", "9477929" ]

[ "The effect of sertraline and environmental context on treating depression and illicit substance use among methadone maintained opiate dependent patients: a controlled clinical trial.", "A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms.", "Doxepin as adjunctive therapy for depressed methadone maintenance patients: a double-blind study.", "Depression and anxiety in heroin addicts: a placebo-controlled study of doxepin in combination with methadone.", "Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts.", "Imipramine as treatment for depression in addicts.", "Imipramine treatment of opiate-dependent patients with depressive disorders. A placebo-controlled trial." ]

[ "Psychiatric comorbidity, particularly depressive disorders, is associated with continued substance use and poor social functioning among methadone maintained patients. Evidence suggests similar neurochemical and environmental pathways may link the two disorders and it is reasonable to hypothesize that pharmacological and environmental factors play important roles in the treating comorbid depression and substance use. The present study tested the efficacy of sertraline for treating syndromally defined depressive disorders among non-abstinent methadone maintained opiate dependent patients. The moderating effects of environmental context on treatment outcome were also examined. Ninety-five patients were randomized in a 12-week, double-blind, placebo-controlled trial of sertraline, a serotonin-selective re-uptake inhibitor. There was no main effect of sertraline on either depression or substance use outcomes. However, sertraline demonstrated significant ameliorative effects on depression among patients with a more positive environment or less negative environment. The odds of being abstinent from heroin and cocaine were greater for patients on sertraline in environments with relatively less adversity. The findings support the hypothesis that contextual factors moderate the efficacy of pharmacological treatment for depression among methadone patients. They also suggest future research should examine a pharmacological treatment that is combined with a behavioral intervention targeting the accessibility of reinforcement or reducing the impact of aversive environmental interactions.", "Depression and antidepressant use are prevalent in methadone maintenance patients (MMPs). However, antidepressant efficacy is not well established in this population. This study examined the efficacy of fluoxetine in improving depressive symptoms and reducing substance use in MMPs.\n Stabilised MMPs scoring over 21 on the Beck Depression Inventory were randomised to receive fluoxetine or placebo over 12 weeks.\n Forty-nine subjects were randomised. In both groups, significant improvements were observed in depression, life functioning, and social impairment over 12 weeks. Poly-drug use improved in completers only. No fluoxetine effects were observed.\n Little evidence supports use of fluoxetine as a treatment for depressive symptoms in MMPs.", "Depression and anxiety can contribute to both drug dependence and reduced retention rates in methadone maintenance programs. In a 5-week double-blind study, the effectiveness of doxepin as an adjunctive treatment was compared to placebo in 46 depressed/anxious patients attending a methadone maintenance program. Doxepin was superior to placebo on Clinical Global Impressions and several factors of the Hamilton Rating Scale for Depression and the Profile of Mood States. No clinically significant potentiation of side effects was observed with the combined administration of doxepin and methadone.", "Narcotic addicts may manifest symptoms of depression that aggravate their addiction. In this double-blind study of 35 mildly depressed patients in a methadone maintenance program, subjects who received doxepin improved significantly more than control subjects. Even in this short-term study, the reduction in depression was associated with a trend toward better performance in other areas of rehabilitation.", "This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts. Methadone-maintained opioid addicts (44) with depression received fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint. In separately analyzing data for the subsample of subjects with the most severe depression, there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use, but no medication effect on either depressive symptoms or on cocaine use. This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population.", "This report describes the results of a placebo-controlled double-blind clinical trial evaluating imipramine hydrochloride, a tricyclic antidepressant, as treatment for depression in methadone-maintained opiate addicts. Forty-six subjects were assigned randomly to either the imipramine or placebo group for up to eight weeks. All patients also received mandatory once weekly group therapy as part of the methadone program. Outcome measures included attrition, depressive symptoms, global improvement, side effects, social functioning, and urine specimen results positive for illicit drugs. The therapeutic response in the two conditions was similar. Addicts receiving either imipramine or placebo experienced a substantial reduction of depressive symptoms during the eight weeks of the study. These findings are compared with other studies that treat depression in addicts and nonaddicts.", "The literature is inconclusive on the role of antidepressant medications in treating drug dependence. Studies have either not focused on depressed patients or have selected patients with depressive disorders based on cross-sectional symptoms rather than a syndromal diagnosis. A clinical trial of an antidepressant was, therefore, conducted on drug-dependent patients with syndromal depression.\n Patients receiving methadone hydrochloride maintenance treatment were selected if they met the criteria for a DSM-III-R depressive disorder that was chronologically primary, had persisted during a past abstinent period or was long-standing, and persisted during at least 1 month of stable methadone treatment. Subjects were randomized to a 12-week, double-blind, placebo-controlled trial of imipramine hydrochloride. A favorable response was defined as a Clinical Global Impression scale score for depression of 2 (\"much improved\") or 1 (\"very much improved\") and at least a 75% reduction in self-reported drug or alcohol use or abstinence.\n One hundred thirty-seven patients were randomized, and 84 completed a minimum adequate trial of at least 6 weeks. Among the 84 adequately treated patients, 57% (24/42) receiving imipramine were rated as responders compared with 7% (3/42) receiving placebo (P < .001). On measures of mood, there was a robust effect of imipramine. Imipramine was superior to placebo on some self-reported measures of substance use and craving, and mood improvement was associated with improvement in self-reported substance use. However, few patients achieved urine-confirmed abstinence.\n Imipramine was an effective antidepressant in patients receiving methadone who were selected via syndromal criteria for depressive illness. Imipramine may reduce substance abuse among patients whose mood improves; however, this effect was less robust." ]

[ "14839578", "1245713", "980602", "2767740", "7722692", "6654697", "9771865", "6892711", "15320919", "13864022", "14672294" ]

[ "The Canadian Red Cross school meal study.", "Evaluation of a ghetto school breakfast program.", "Nutritional supplementation of disadvantaged elementary-school children.", "Effect of mid-day meal programme on physical growth & mental function.", "School breakfast improves verbal fluency in undernourished Jamaican children.", "An evaluation of giving the Jamaican government school meal to a class of children.", "Nutrition and education: a randomized trial of the effects of breakfast in rural primary school children.", "A randomised controlled trial of the effect of the provision of free school milk on the growth of children.", "A national evaluation of school breakfast clubs: evidence from a cluster randomized controlled trial and an observational analysis.", "Rural nutrition studies in Indonesia. IX. Feeding trial on schoolboys.", "Animal source foods improve dietary quality, micronutrient status, growth and cognitive function in Kenyan school children: background, study design and baseline findings." ]

[ "nan", "A program was initiated to provide a free breakfast at a ghetto elementary school. Community support was achieved at the expense of randomization of study subjects. While no significantly greater increase in school attendance or performance was detected in comparison with a control school, none of the students was malnourished and diets of students in the control school were as adequate as those in the breakfast school. Thus, it cannot be concluded that school breakfast programs would not benefit malnourished children or teen-agers who most often go without breakfast.", "nan", "The effect of food supplementation in rural primary school children was studied on physical growth and mental functions. Children (146) received 450-500 calories with 10-12 g of protein for an average of 172 days a year, for 2 yr (1984-1986). Height was found not to differ significantly in the supplemented group as compared to controls. However, there was marginally better weight gain. More children in the supplemented group remained in grade I in contrast to the controls who shifted to grade II nutritional status after 2 yr. Children receiving the supplementation showed marginal increment in full scale, verbal and performance IQ. The improvement was significant for all subtests except for comprehension and maze tests. The observations on unstructured Piagetian developmental tasks also indicated that the performance of children on task conservation of liquid was improved marginally after supplementation. However, on Bender Gestalt test, no change was observed. The scores on arithmetic achievement test showed improvement of 12-14 points in the supplementation group. It appears that nutrition supplementation is beneficial for better school attendance, and reduction in the drop out rate; it also improves intelligence and cognitive function to a marginal extent. However, as this age group falls in the slow growth period, no catch up was observed in physical growth.", "School feeding programs exist in many countries, but few have been properly evaluated. In this study, the short-term effects of breakfast on children's cognitive functions were examined. The subjects were 97 undernourished (weight-for-age < or = -1 SD of reference) and 100 adequately nourished (weight-for-age > -1 SD) children in four primary schools in rural Jamaica. The children were randomly assigned to a group provided with breakfast or a group given a quarter of an orange as a placebo, and then given a battery of four cognitive function tests. After a few weeks the treatments were reversed and the tests repeated. Undernourished children's performance improved significantly on a test of verbal fluency when they received breakfast, whereas that of the adequately nourished children did not change (breakfast x group interaction, P < 0.05). There were no other effects of breakfast on test scores. The findings extend those of a previous Jamaican study conducted under more controlled conditions, and support the targeting of school meals to undernourished children.", "We evaluated the effects of giving the standard Jamaican government school meal to a class of school children. Unlike many other school-feeding studies, this project was carefully controlled and carried out with undernourished children who had low levels of school attendance and achievement. In spite of this, no improvement was found in the children's nutritional status as reflected by weight for age. However, small benefits were found in attendance and school achievement. These findings remained when sex, age, improvements over the previous term, and the effects of 'benevolent attention' were taken into account.", "Hunger during school may prevent children in developing countries from benefiting from education. Although many countries have implemented school feeding programs, few programs have been rigorously evaluated. We conducted a randomized, controlled trial of giving breakfast to undernourished and adequately nourished children. The undernourished group comprised 407 children in grades 2-5 in 16 rural Jamaican schools (weights-for-age < or = -1 SD of the National Center for Health Statistics references) and the adequately nourished group comprised 407 children matched for school and class (weights-for-age >-1 SD). Both groups were stratified by class and school, then randomly assigned to breakfast or control groups. After the initial measurements, breakfast was provided every school day for 1 school year. Children in the control group were given one-quarter of an orange and the same amount of attention as children in the breakfast group. All children had their heights and weights measured and were given the Wide Range Achievement Test before and after the intervention. School attendance was taken from the schools' registers. Compared with the control group, height, weight, and attendance improved significantly in the breakfast group. Both groups made poor progress in Wide Range Achievement Test scores. Younger children in the breakfast group improved in arithmetic. There was no effect of nutritional group on the response to breakfast. In conclusion, the provision of a school breakfast produced small benefits in children's nutritional status, school attendance, and achievement. Greater improvements may occur in more undernourished populations; however, the massive problem of poor achievement levels requires integrated programs including health and educational inputs as well as school meals.", "A randomised controlled study was carried out of the effect on growth of the provision of free milk supplements to schoolchildren aged 7 and 8. In selecting children for this study, the aim was to identify those whose socioeconomic circumstances might place them at a disadvantage for growth. Five hundred and eighty-one-children were selected from schools where a high proportion of the pupils received free school meals, and from families with four or more children. The subjects were randomly allocated to receive a third of a pint (190 ml) of free milk daily for six school terms or to a control group. The mean difference in height gain at the end of twenty-one-and-a-half months was 3% or 2.93 mm (P less than 0.05) in favour of the children provided with free milk. The mean difference in weight gain was 130 g (P greater than 0.05) in their favour. The height and weight gain associated with the provision of free mild was very small in the study population, and it is therefore likely that the benefit to growth of providing free milk for the whole unselected population of schoolchildren of these ages would be even smaller.", "To measure the health, educational and social impacts of breakfast club provision in schools serving deprived areas across England.\n A cluster randomized controlled trial and an observational analysis.\n England, the UK. Intervention: funding to establish a school-based breakfast club vs. control (no funding).\n Intention to treat analysis showed improved concentration (Trail Making Test Part A) amongst the intervention group at 3 months. Fewer pupils within the intervention group reported having skipped classes within the last month and fewer pupils within the intervention group reported having skipped 1 or more days of school within the last month at 1 year. Observational analysis at 1 year showed a higher proportion of primary-aged breakfast club attendees reported eating fruit for breakfast in comparison to non-attendees. A higher proportion of breakfast club attendees had borderline or abnormal conduct and total difficulties scores (primary-aged pupils) and prosocial score (secondary-aged pupils).\n Analyses revealed a mixed picture of benefit and apparent disbenefit. This study illustrated the challenges of evaluating a complex intervention in which the evaluators had less control than is usual in randomized trials over recruitment, eligibility checking and implementation. If the impact of new policy initiatives is to be assessed using the most robust forms of evaluation, social policy needs to be organized so that evaluations can be constructed as experiments. This is likely to prove most difficult where the perceived value of implementing an intervention rapidly is high.", "nan", "A previous longitudinal three-country study in Egypt, Kenya and Mexico found significant positive associations between intake of animal source foods (ASF) and growth, cognitive development and physical activity. To test for a causal relationship, a controlled school feeding intervention study was designed to test the hypotheses that ASF would improve micronutrient status, growth and cognitive function in Kenyan primary school children. Twelve rural Kenyan schools with 554 children were randomized to four feeding interventions using a local vegetable stew as the vehicle. The groups were designated as Meat, Milk, Energy and Control, who received no feedings. Feeding was carried out on school days for seven terms during 21 mo. Preintervention baseline measures included nutritional status, home food intake, anthropometry, biochemical measures of micronutrient status, malaria, intestinal parasites, health status and cognitive and behavioral measures. The measurements of each child were repeated at intervals over 2 y. Baseline data revealed stunting and underweight in approximately 30% of children and widespread inadequate intakes and/or biochemical evidence of micronutrient deficiencies, particularly of iron, zinc, vitamins A and B-12, riboflavin and calcium. Little or no ASF were eaten and fat intake was low. Malaria was present in 31% of children, and hookworm, amebiasis and giardia were widely prevalent. The outcomes measured were rates of change or increase during the intervention in cognitive function, growth, physical activity and behavior and micronutrient status. Hierarchical linear random effects modeling was used for analysis of outcomes." ]

[ "6349560", "2862316", "417754", "53370", "4206451", "4211056", "413639" ]

[ "Failure of meningococcal vaccination to stop the transmission of meningococci in Nigerian schoolboys.", "Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine.", "Prevention of secondary cases of meningococcal disease in household contacts by vaccination.", "Effect of group-A meningococcal vaccine in army recruits in Finland.", "A controlled field trial of a serogroup A meningococcal polysaccharide vaccine.", "A serogroup A meningococcal polysaccharide vaccine: studies in the Sudan to combat cerebrospinal meningitis caused by Neisseria meningitidis group A.", "A second controlled field trial of a serogroup A meningococcal polysaccharide vaccine in Alexandria." ]

[ "A combined group A and group C meningococcal polysaccharide vaccine was given to 438 Nigerian schoolboys shortly before an outbreak of group A meningococcal disease occurred in their school. Four months after vaccination the carriage rate of group A meningococci among vaccinated subjects (11%) was no different from that found among the controls (12%), although a good antibody response to both components of the vaccine was observed. One case of group A meningococcal disease was recorded amongst 438 vaccinated subjects while five cases occurred among 874 controls.", "Sequential case-control studies were used to monitor changes in the clinical protection induced by group A meningococcal polysaccharide vaccine over a 3-year period. Overall, vaccine efficacy declined from 87% 1 year after vaccination to 70% and 54% at 2 and 3 years, respectively. When stratified by age at time of vaccination the data showed that, although vaccine efficacy remained high in children greater than or equal to 4 years of age (vaccine efficacy 85%, 74%, and 67% at 1, 2, and 3 years after vaccination, respectively), it declined dramatically in those less than 4 years of age at time of vaccination (vaccine efficacy 100%, 52%, and 8%, respectively, at 1, 2, and 3 years after vaccination). Thus, a single dose of group A meningococcal vaccine does not yield lasting clinical protection in children less than 4 years of age.", "Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.", "During an epidemic caused by group-A, sulphonamide-resistant meningococci in Finland, group-A polysaccharide vaccine was administered in 1974 to 16 458 recruits of the Armed Forces, leaving 20 748 as controls. Specific antibody response was good, and after vaccination only 1% of the men were without anti-meningococcal group-A antibodies. Pharyngeal carriage of the epidemic strain was low, about 1-5%, in the men when entering service. Group-A meningococcal disease occurred during the nine months' mean observation period in 1 of the vaccinated men (an annual incidence of 11 per 100 000) and in 8 of those not vaccinated (71 per 100 000), indicating 89% protective effect of the vaccine. Furthermore, the total number of cases of group-A meningococcal disease was reduced to non-epidemic levels at a time when 36% of the men in service were vaccinated, and has remained low for the next twelve months even though the epidemic in the general population continued.", "A controlled field trial of a serogroup A meningococcal polysaccharide vaccine was conducted at three locations in Egypt during the winter cerebrospinal meningitis (CSM) season of 1971-72. The study population consisted of schoolchildren 6-15 years of age. No cases of serogroup A meningococcal CSM occurred in the group of students vaccinated with the test vaccine whereas 8 cases occurred in the control group vaccinated with tetanus toxoid, and 151 cases occurred in an unvaccinated contrast group. The case rate was significantly different between the test and control groups as well as between the test and contrast groups but was similar between the control and contrast groups. The previously demonstrated safety of the vaccine was confirmed. A significant serological response was elicited in the majority of the vaccinated students.", "Vaccination against cerebrospinal meningitis (CSM) has regained interest with the use of capsular polysaccharides (or polyosides) of the meningococcus as specific immunizing agents. These compounds proved to be effective in the USA against meningitis caused by Neisseria meningitidis serotype C. This study considers whether the polysaccharides of the serotype A meningococcus, which is prevalent in the African CSM belt, could be protective in epidemic conditions. Taking advantage of the usual seasonal peak of CSM cases, controlled field trials were undertaken in the Sudan early in 1973. 21 640 persons were vaccinated, half of them with a meningococcal polyoside A vaccine and the other half with tetanus toxoid as a placebo. In the former group there were no cases of meningitis, whereas in the latter 10 cases were reported, of which 7 were confirmed by laboratory tests. These studies indicate that the meningococcal polyoside A vaccine is efficient in epidemic conditions and could be used to control outbreaks of meningococcal meningitis.", "The encouraging results of an earlier controlled field trial of the serogroup A meningococcal polysaccharide vaccine in the prevention of clinical disease prompted this study, the aim of which was to evaluate further the effectiveness of another lot of this type of vaccine, the duration of immunity, and the effectiveness against meningococcal carriage. A controlled field trial was carried out in early 1973 on 176 646 schoolchildren 6-15 years of age, of whom half received the serogroup A polysaccharide vaccine and the other half tetanus toxoid as a control. The incidence of cerebrospinal meningitis caused by serogroup A meningococci was 89% lower in the immunized group than in the controls for one year only. With regard to its effect on carriage, the vaccine was found to reduce to less than half the rate of new acquisition of serogroup A meningococci during the period immediately following immunization. The duration of the carrier state was also shortened in the immunized group." ]

[ "2522746", "2693404", "8442966", "2639667", "17635971", "15564951", "16265829", "2718002" ]

[ "Prevention of postdural puncture headache after spinal anaesthesia for extracorporeal shockwave lithotripsy. An assessment of prophylactic epidural blood patching.", "Epidural blood patch in the treatment of post dural puncture headache: a double blind study.", "Headache prevention following accidental dural puncture in obstetric patients.", "Unintentional dural puncture and prophylactic epidural blood patch in obstetrics.", "Epidural blood patch in post dural puncture headache: a randomised, observer-blind, controlled clinical trial.", "Efficacy of a prophylactic epidural blood patch in preventing post dural puncture headache in parturients after inadvertent dural puncture.", "Conventional treatment or epidural blood patch for the treatment of different etiologies of post dural puncture headache.", "Prophylactic epidural blood patch in parturients." ]

[ "The prevention of postdural puncture headache after spinal anaesthesia for extracorporeal shockwave lithotripsy was investigated by a controlled clinical trial which compared epidural injection of 10 ml of autologous blood with 10 ml of normal saline immediately after intrathecal injection of local anaesthetic. The incidence of postdural puncture headache was 8.3% in the group that received blood compared with 45% in the group that received saline, a significant reduction (p less than 0.01). The incidences of backache and lower limb paraesthesiae were similar in both groups. No serious complications were reported.", "A randomised double blind controlled trial of 'epidural blood-patch' as treatment for post-dural puncture headache is presented. The method was successful in 11 out of 12 cases on its first application, the twelfth patient being relieved by a second procedure. None of six patients reported benefit from a 'sham' procedure. The rationale for the use of the technique is discussed.", "To evaluate the efficacy of a prophylactic saline patch and a prophylactic blood patch in prevention of headache following accidental dural puncture in obstetric patients.\n Prospective, randomized, single-blind study on dural puncture headache occurrence and cessation.\n Inpatient obstetric unit at a metropolitan medical center.\n Seventy-four inpatients who underwent vaginal delivery or cesarean section following accidental dural puncture during administration of epidural anesthesia for labor and delivery.\n Group 1 (n = 24), the control group, received fluids and analgesics. Group 2 (n = 30) received prophylactic epidural saline (40 to 60 ml) through the epidural catheter following completion of the obstetric procedure. Group 3 (n = 20) received autologous blood (15 ml) via epidural catheter following completion of the obstetric procedure.\n In Group 1, 21 of 24 patients (87.5%) developed headaches, with conservative management. In Group 2, 20 of 30 patients (66.7%) developed headaches, and in Group 3, 1 of 20 patients (5%) developed a headache.\n The results of this study suggest that the administration of a prophylactic epidural blood patch is highly effective in the prevention of headaches following dural puncture, with headache frequency reduced from 87.5% to 5%.", "nan", "To determine the efficacy of epidural blood patch (EDBP) for the treatment of post dural puncture headache (PDPH).\n We randomised 42 patients who presented with PDPH, lasting 24 h to 1 week, to receive EDBP (n = 19) or conservative treatment (n = 23). The primary end point was any headache at 24 h after the start of treatment. Secondary end points were presence and severity of headache after 1 week. Stratified Mantel-Haenzel analysis was used to adjust for confounders.\n Two patients refused to participate directly after randomisation and allocation to conservative treatment. They were excluded from the study. At 24 h after the start of treatment, headache was present in 11 (58%) patients allocated to EDBP and in 19 (90%) patients allocated to conservative treatment (RR 0.64, 95% CI 0.43 to 0.96). At day 7, headache was present in three (16%) patients allocated to EDBP and in 18 (86%) allocated to conservative treatment (RR 0.18, 95% CI 0.06 to 0.53). Headache was mild in all three EDBP patients, but in 10 of 18 conservatively treated patients who had not recovered by day 7 it was classified as moderate or severe. Adjustments for confounders did not affect these results.\n EDBP is an effective treatment for PDPH. It offers complete resolution of symptoms in a large proportion of patients. In the remaining patients, it reduces headache severity and allows them to return to their everyday activities.", "Postdural puncture headache (PDPH) occurs in up to 80% of parturients who experience inadvertent dural puncture during epidural catheter placement. The authors performed a randomized double blind study to assess the effect of prophylactic epidural blood patch on the incidence of PDPH and the need for therapeutic epidural blood patch.\n Sixty-four parturients who incurred inadvertent dural puncture were randomized to receive a prophylactic epidural blood patch with 20 ml autologous blood (prophylactic epidural blood patch group) or a sham patch (sham group). Subjects were evaluated daily for development of PDPH for a minimum of 5 days after dural puncture. Those who developed a PDPH were followed daily for a minimum of 3 days after resolution of the headache. Subjects with moderate headaches who reported difficulties performing childcare activities and all those with severe headaches were advised to receive a therapeutic epidural blood patch.\n Eighteen of 32 subjects in each group (56%) developed PDPH. Therapeutic blood patch was recommended in similar numbers of patients in each group. The groups had similar onset time of PDPH, median peak pain scores, and number of days spent unable to perform childcare activities as a result of postural headache. The median duration of PDPH, however, was shorter in the prophylactic epidural blood patch group.\n A decrease in the incidence of PDPH or the need for criteria-directed therapeutic epidural patch was not detected when a prophylactic epidural blood patch was administered to parturients after inadvertent dural puncture. However, prophylactic epidural blood patch did shorten the duration of PDPH symptoms.", "Post dural puncture headache (PDPH) represents a complication of anesthesia (with an increased incidence in obstetric patients) or as the consequence of a diagnostic lumbar puncture. The aim of the present study was to evaluate the efficacy of the epidural blood-patch (EBP) versus the conventional medical treatment of post-anesthetic headaches also including the PDPH following a diagnostic puncture, a category of patients rarely referred to the anesthesia consultation in our hospital because it was believed that they might have equal benefit from conventional measures due to the smaller size of needles used. We studied in a prospective, randomized, double-blinded manner 32 obstetric and non-obstetric patients with PDPH having the onset of the symptoms 24 hours before the inclusion in the study. The patients were randomly divided in two groups: group A (16 patients) receiving conventional treatment (oral and intravenous fluid replacement, non-steroidal anti-inflammatory drugs--NSAIDs--, caffeine) and group B (16 patients) in whom an epidural blood-patch was performed. The intensity of the headache was evaluated using a visual analogue scale (VAS) from 0-10, before, 2 hours and 24 hours after the EBP. There were no statistical differences concerning the demographic data and the cause of PDPH between the groups (p > 0.05). The intensity of PDPH was similar before performing the EBP (p > 0.05), with a value on VAS of 8.2 +/- 1,4. in group A and 8,0 +/- 1.6 in group B. Two hours after the treatment, the intensity of headache on VAS diminished extremely significant (p < 0.0001): in group B the value was 1.0 +/- 0,18 versus 8.2 +/- 1.4 in group A. The difference recorded after 24 hours remained statistically significant (p < 0.0001): the VAS scores were 0.7 +/- 0,16 and 7.8 +/- 1.2 respectively. The epidural blood patch represents the first choice treatment of PDPH no matter the etiology, being significantly superior to the conventional treatment which did not affect pain scores. In severe PDPH there is no reason to delay the EBP more than 24 hours after the diagnosis as all except two patients of the conventional treatment group required blood patching following the study period.", "nan" ]

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[ "A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction.", "Impact of intensified dietary therapy on energy and nutrient intakes and fatty acid composition of serum lipids in patients with recently diagnosed non-insulin-dependent diabetes mellitus.", "Does self-monitoring of blood glucose levels improve dietary compliance for obese patients with type II diabetes?", "[Intensive basic therapy decreases the need for drug treatment and improves glucose control: an important result of the diabetes intervention study].", "Long-term comparison of three dietary prescriptions in the treatment of NIDDM.", "Effect of metabolic control on autonomic function in obese patients with newly diagnosed type 2 diabetes.", "[Coronary heart disease and insulin concentration in type II diabetic patients--results of a diabetes intervention study].", "Prospective evaluation of HDL cholesterol changes after diet and physical conditioning programs for patients with type II diabetes mellitus.", "Effects of lifestyle modifications on patients with type 2 diabetes: the Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report.", "Effects of diet and exercise interventions on control and quality of life in non-insulin-dependent diabetes mellitus.", "Reducing cardiovascular disease risk with diet.", "The maintenance of improved metabolic control after intensified diet therapy in recent type 2 diabetes.", "Efficacy of dietary instructions in newly diagnosed non-insulin-dependent diabetic patients. Comparison of two different patient education regimens.", "Self-monitoring of blood glucose in overweight type 2 diabetic patients.", "Work absenteeism in type 2 diabetes mellitus: results of the prospective Diabetes Intervention Study.", "Improved fibrinolysis by intense lifestyle intervention. A randomized trial in subjects with impaired glucose tolerance.", "Effects of a very-low-calorie diet on long-term glycemic control in obese type 2 diabetic subjects.", "A \"family-based\" approach to the treatment of obese type II diabetic patients.", "Exercise in a behavioural weight control programme for obese patients with Type 2 (non-insulin-dependent) diabetes.", "Long-term effects of modest weight loss in type II diabetic patients.", "Prospective comparison of modified fat-high-carbohydrate with standard low-carbohydrate dietary advice in the treatment of diabetes: one year follow-up study.", "Metabolic and dietary determinants of serum lipids in obese patients with recently diagnosed non-insulin-dependent diabetes.", "Diminished weight loss and behavioral compliance during repeated diets in obese patients with type II diabetes.", "Effectiveness of a behavioral weight control program for blacks and whites with NIDDM.", "Insulin sensitivity as a predictor of weight regain.", "Year-long weight loss treatment for obese patients with type II diabetes: does including an intermittent very-low-calorie diet improve outcome?", "Nutritional management of cardiovascular risk factors. A randomized clinical trial.", "Group education for obese patients with type 2 diabetes: greater success at less cost.", "Dietary compliance and cardiovascular risk reduction with a prepared meal plan compared with a self-selected diet.", "Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM.", "Early lifestyle intervention in patients with non-insulin-dependent diabetes mellitus and impaired glucose tolerance.", "Behavior change, weight loss, and physiological improvements in type II diabetic patients.", "Sex differences in weight loss among adults with type II diabetes mellitus.", "Group visits improve metabolic control in type 2 diabetes: a 2-year follow-up.", "Lifestyle intervention by group care prevents deterioration of Type II diabetes: a 4-year randomized controlled clinical trial.", "Effects of a behavioral weight loss program stressing calorie restriction versus calorie plus fat restriction in obese individuals with NIDDM or a family history of diabetes.", "[Intensified therapy of newly detected maturity onset diabetes].", "The effect of weight loss on change in waist-to-hip ratio in patients with type II diabetes.", "Habitual physical activity, aerobic capacity and metabolic control in patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus: effect of 1-year diet and exercise intervention.", "Physical activity and fibrinogen concentration in newly diagnosed NIDDM." ]

[ "To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons.\n In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD.\n The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance.\n After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group.\n Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.", "Compliance with dietary recommendations and the effect of intensified dietary therapy on energy and nutrient intakes and fatty acid composition of serum lipids were studied in 86 obese subjects (aged 40 to 64 years) with recently diagnosed non-insulin-dependent diabetes mellitus (NIDDM). After three months of basic education, the subjects were randomly separated into an intervention group (n = 40) and a conventional treatment group (n = 46). Members of the intervention group participated in 12 months of intensified education; those in the conventional group visited local health centers. Compliance with dietary instructions was monitored through food records. Intensified dietary therapy resulted in greater weight loss, better metabolic control, and a less atherogenic lipid profile than conventional treatment. Intake of energy and saturated fatty acids tended to decline in the intervention group. A higher percentage of patients in the intervention group had a total fat intake of 30% of energy or less after 15 months (32.5% [12 of 38] vs 17.4% [8 of 46]). Similarly, more patients in the intervention group had a saturated fatty acid intake of 10% or less of total energy intake at the end of the study (35.0% [13 of 38] vs 8.7% [4 of 46]). The mean dietary cholesterol intake was within recommendations in both groups at the end of the study. The relative percentage of linoleic acid of serum lipids increased significantly and the relative percentage of palmitic acid of serum triglycerides, phospholipids, and cholesterol esters decreased in the intervention group. These changes indicate that intensified dietary therapy improved the quality of fat in the diet of patients with NIDDM.", "Self-monitoring of blood glucose levels is currently being recommended for obese patients with type II diabetes to improve weight loss and glycemic control. To determine whether self-monitoring of blood glucose levels improves dietary compliance in these patients, 50 obese patients with type II diabetes were randomly assigned either to a standard behavioral weight control program or to a weight control program that included self-monitoring of blood glucose levels and focused on the weight-blood glucose relationship. Both groups lost significant amounts of weight and maintained their losses for at least one year; reductions in medication could be made for 70 percent of patients. These data suggest that the behavioral weight control used in this study may be of benefit to patients with type II diabetes. However, there was no evidence that the addition of self-monitoring of blood glucose levels to the treatment program improved the outcome in terms of weight loss, reduction in medication, dietary compliance, or mood state.", "In a period of five years in the diabetes intervention study (DIS), 1,139 diabetics aged 30-55 years, who in a 6-week screening phase had been classified as dietetically manageable, were treated in a controlled randomized study with intensified non-medicamentous basic therapy and--in a double blind trial--with 1,6 g clofibric acid. The essential components of the basic therapy were a fat-modified diet (so-called prudent diet) and recommendations for endurance training. Thus in comparison to the control group we succeeded in performing a ca. 40% decrease of the application of oral antidiabetic drugs. The fasting blood values were, nevertheless, with 155 mg% significantly lower than in the control group (169 mg%). Clofibric acid had no influence neither on the necessity to use insulin or oral antidiabetic drugs nor to the control of glycaemia.", "To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period.\n Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured.\n In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups.\n In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention.", "To evaluate the effect of diet therapy and physical exercise on autonomic nervous function in newly diagnosed Type 2 diabetes, we followed 83 middle-aged obese patients (48 men, 35 women) for a 15-month period. After a 3-month basic education programme the patients were randomized to one of two groups for comparison of standard treatment given by community health centres (conventionally treated group) and intensive dietary and exercise education (intervention group). Autonomic function was assessed by heart rate variability during deep breathing (expiration/inspiration ratio, E/I), and by systolic blood pressure response to standing up. The intensively treated women (n = 18) had the best blood glucose throughout the study, and this was the only group to show an improvement in E/I ratio (1.19 +/- 0.03 vs 1.30 +/- 0.05, mean +/- SEM, p < 0.05). None of the groups showed any significant change in systolic blood pressure response to standing up. For further analyses, the original groups were combined and thereafter divided into those with declining fasting blood glucose during the intervention phase (n = 39) and into those with no change or increase in blood glucose level (n = 44). The group with improving blood glucose level showed an increase in E/I ratio (1.22 +/- 0.02 vs 1.28 +/- 0.03, p < 0.01) while in the other group E/I ratio remained unchanged (1.21 +/- 0.02 vs 1.20 +/- 0.02). The difference in E/I ratio between these two groups was significant at 15 months (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "There is experimental, clinical and epidemiological evidence that elevated insulin levels are associated with development of atherosclerosis. Early results came from studies in non-diabetics, but the situation with respect to diabetes is more complex and not so clear. The Diabetes Intervention Study is a population-based follow-up study in newly detected type II diabetics (30- to 55-yr-old). After 5 years 431 men and 320 women received a complex check up with oral glucose tolerance tests and measurements of plasma insulin and glucose levels, fasting and 2h post-load. Regarding the metabolic parameters, the fasting and postprandial insulin levels were higher among the patients having coronary heart disease (15% of men, 36% of women), as compared to patients without this disease. In multivariate analysis sex, age, antihypertensive treatment, blood pressure, body mass index, and fasting insulin levels were independently associated with the prevalence of coronary heart disease in patients with non-insulin dependent diabetes mellitus (NIDDM) treated with diet and/or oral antidiabetics. Body mass index and triglycerides were the only variables that independently correlated to insulin: fasting insulin = 0.4 (body mass index) + 0.1 (triglycerides) - 4,2. In future prospective studies of diabetics relating insulin concentrations to the development of vascular disease are of particular interest and necessity. Because hyperinsulinemia may contribute to accelerated atherosclerosis in NIDDM-patients, the aim of the treatment of type II-diabetes should be to correct hyperglycemia without aggravating insulin levels and other cardiovascular risk factors.", "High-density lipoprotein (HDL) cholesterol is known to be low in patients with diabetes mellitus. Low HDL levels are correlated with premature cardiovascular mortality in several major epidemiologic studies and many investigators believe increases in HDL cholesterol may reduce the risk of coronary heart disease. We evaluated dietary and exercise interventions in relation to HDL cholesterol in patients with type II diabetes mellitus. Sixty-five volunteers were randomly assigned to one of four experimental conditions: diet, exercise, diet plus exercise, or education control. Three months after entering the program, those exposed to the dietary intervention had significant increases in HDL cholesterol. HDL increases for the other two treatment groups did not differ significantly from the education control.", "Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes.\n The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results.\n The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care.\n The study enrolled 2 205 patients with previously diagnosed type 2 diabetes.\n The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer.\n Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year.\n Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available.\n The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.", "Evidence suggests that diet and exercise are associated with improved glucose tolerance for patients with non-insulin-dependent diabetes mellitus (NIDDM). Seventy-six volunteer adult patients with NIDDM were each assigned to one of four programs: diet, exercise, diet plus exercise, or education (control). Each program required ten weekly meetings. Detailed evaluations were completed prior to the program and after three, six, 12, and 18 months. Evaluations included various psychosocial measures, measures of the quality of life, and fasting blood glucose, glycosylated hemoglobin, and relative weight determinations. Of the 76 original participants, 70 completed the 18-month follow-up study. At 18 months, the combination diet-and-exercise group had achieved the greatest reductions in glycosylated hemoglobin measures. In addition, this group showed significant improvements on a general quality of life measure. These improvements were largely uncorrelated with changes in weight. The authors conclude that the combination of dietary change and physical conditioning benefits NIDDM patients, and that the benefits may be independent of substantial weight loss.", "Past research efforts to determine the influence of the diet on cardiovascular (CV) health have focused on the individual roles of specific dietary components with debatable success. Awareness of the impact and complexity of nutrient interactions has expanded in recent years to include assessment of dietary patterns as they contribute to lower CV disease risk.\n In a series of multicenter studies, we compared a comprehensive, prepared meal plan, formulated to meet recommended intake levels of macro- and micronutrients, with a self-selected diet based on the exchange system. The three studies comprised adult participants with hypertension, hyperlipidemia, and type 2 diabetes (n = 560, 251, and 330, respectively). The first two studies (10 weeks) varied by the amount of contact with study personnel, and the third study assessed long-term effects over 52 weeks. Outcome measures included: blood pressure, lipid and lipoprotein levels, glycemic control, homocysteine, compliance, quality of life, and weight.\n The first study demonstrated significant improvements in all measures, with greater improvements with the prepared meal plan compared with the self-selected diet. The second study, designed to parallel the contact frequency that would occur in a real world clinical setting, also produced significant improvements in multiple CV risk factors. In the long-term study, in addition to sustained improvements in risk factors, significant weight loss was achieved and maintained over the 52 weeks.\n These trials demonstrate that regular consumption of a nutritionally complete diet offers multiple, concurrent clinical benefits for reducing CV disease risk and body weight.", "Altogether 86 patients with recently diagnosed NIDDM, aged 40-64 years were randomised after 3 months of basic education to intensified diet (Int. group, 21 men, 19 women) or conventional treatment groups (Conv. group, 28 men, 18 women). The aim was to examine whether an intensified diet education would result in a better metabolic control and greater reduction in cardiovascular risk factors than conventional treatment for obese patients with recently diagnosed type 2 diabetes mellitus. Furthermore, both groups were re-examined after a second year of observation period to find out the maintenance of the results after intervention. After basic education, Int. group participated in 12-months diet education, while Conv. group was treated in local health centres. During the intervention period, only Int. group showed further weight reduction. Only 20% of patients in Int. and 6% of patients in Conv. group had BMI < 27 kg/m2 at the end of the intervention, while 75% of patients in Int. and 52% of patients in Conv. group had achieved a good metabolic control (fasting blood glucose < 6.7 mmol/l; P = 0.005 between groups). Serum total cholesterol did not change significantly, but the changes in HDL-cholesterol, triglycerides and apolipoprotein B level were significant in Int. group only. The proposed acceptable values for serum lipids were achieved by 52 to 88% of patients without major differences between the two groups. During the second year of observation, weight gained in both groups and a deterioration was seen in metabolic control. Despite that a greater proportion of patients in the Int. group still was in good metabolic control (55.3% vs. 31.8%, P = 0.016), furthermore Int. group was receiving less frequently oral drugs for hyperglycaemia than Conv. group. No differences in serum lipids were observed between the groups after the observation period. HDL-cholesterol showed a persistent improvement in both groups.", "Eighty consecutive newly diagnosed non-insulin-dependent diabetic patients were randomly allocated into two groups to compare two different patient education regimens. One group received individual dietary instructions by a nurse and the other a short, written leaflet given by a doctor. The principal aim of the dietary instructions was weight reduction. A significant weight loss and improvement in the control of diabetes occurred in both groups, and these changes were similar in the two groups. At the end of one year's follow-up, however, only 25% of the patients were satisfactorily controlled (fasting blood glucose less than or equal to 6.0 mmol/l). The degree of weight loss correlated only weakly with the improvement in the metabolic control. The degree of obesity and insulin secretion capacity as measured at the beginning of the study did not predict the improvement of glycaemic control during the study. At the end of the study a significant improvement was observed in serum lipids of patients with good control (fasting blood glucose less than or equal to 6.0 mmol/l) or weight loss (greater than 5 kg). In conclusion, both brief, written and individual dietary instructions induced a significant weight loss as well as improved glucose and lipid metabolism in newly diagnosed non-insulin-dependent diabetic patients, but satisfactory metabolic control was achieved only in a minority of the patients.", "Self-monitoring of blood glucose (SBGM) is widely recommended for both type 1 and type 2 diabetic patients despite the lack of evidence of benefit in glucose control or as an aid in weight loss in type 2 subjects. This study tested the hypothesis that combined use of SMBG and dietary carbohydrate (CHO) counting, using the blood monitoring results to shape dietary CHO quotas, is beneficial in managing type 2 diabetes. Twenty-three overweight (body mass index, BMI 27.5-44 kg/m2) patients aged 40-75 participated in a 28-week behavioral weight control program. Baseline hemoglobin HbA1c ranged between 9.5% and 13.5% (normal range 5.5%-7.7%). Subjects were matched for weight, sex, and HbA1c and assigned to small (4-8 participants) groups which met weekly for 12 weeks and then monthly for 16 weeks. After 8 weeks, the groups were randomized either to continue the behavioral program or to have SMBG and dietary CHO counting. Glucose monitoring was performed 6 times daily (pre- and 2 h postprandially) for the first month, focusing on the meal increment and correlating this to dietary CHO intake. Weight loss was identical in both groups during the year of follow-up. The HbA1c level showed a progressive decline in experimental subjects (P < 0.05), whereas there was no improvement in control subjects.", "Newly diagnosed mild Type 2 diabetic patients, aged 30-55 years, were included in the prospective, multi-centre Diabetes Intervention Study. They were randomly allotted to either an intervention group receiving intensified health education or to a control group on usual care. This paper reports the incidence, duration of and causes for absence from work due to any disease in the patients who were working during the first 5-year follow-up. Data from 817 patients could be taken into account. 14.5% of the intervention patients and 17.3% of the control patients had never been on the sick list. Those patients who had undergone intensified health education were listed sick less often. Women showed a higher work absenteeism in either group; they had higher blood pressure and higher body mass index at entry. Cardiovascular diseases and musculo-skeletal disorders were major reasons for absence from work. However, when compared to the general population, these Type 2-diabetic patients were approximately four times more often on the sick list. Thus, the health education programme of the Diabetes Intervention Study was shown to be effective with respect to work absenteeism. Teaching patients is recommended as an important part of the therapeutic regimen.", "To assess the effects of lifestyle intervention on cardiovascular risk factors in general and especially on fibrinolysis.\n Randomized clinical study.\n A total of 186 subjects with impaired glucose tolerance and obesity.\n The intervention programme included a low-fat, high-fibre diet and regular physical exercise. Half of the participants (n = 93) took part in a one-month learning and training session using different behavioural modification techniques and conducted in a full-board wellness centre (intense intervention group). The other half (n = 93) was randomized a one-hour counselling session with a specially trained nurse (usual care group). Follow-up was carried out after 12 months.\n Body weight, oxygen consumption, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator (tPA) antigen, fibrinogen and fasting plasma insulin measured at the start of the programme and at follow-up after 1 year.\n The intense intervention group had a mean weight decline by 1 year of 5.4 kg compared to 0.5 kg in the usual care group. Oxygen consumption in the intense group increased 10% vs. a 1% decline in the usual care group. In the intense group, PAI-1 activity decreased 31% (-10.1 U mL(-1)), which was significantly more than in the usual care group (12%; -3.0 U mL(-1)). The corresponding reductions in tPA antigen were 14% (-1.65 microg L(-1)) and 6% (-0.69 microg L(-1)).\n The present randomized study shows that an intense lifestyle programme has sustained beneficial effects on fibrinolysis.", "We tested the hypothesis that the use of a very-low-calorie diet (VLCD) in combination with behavior modification would promote long-term glycemic control in obese type 2 diabetic subjects. Thirty-six diabetic subjects were randomly assigned to a standard behavior therapy program or to a behavior therapy program that included an 8-week period of VLCD. The behavior therapy group consumed a balanced diet of 4200 to 6300 J/d throughout the 20-week program. The VLCD group consumed a balanced diet of 4200 to 6300 J for weeks 1 to 4, followed by a VLCD (1680 J/d of lean meat, fish, and fowl) for weeks 5 to 12. The VLCD group then gradually reintroduced other foods during weeks 13 to 16 and consumed a balanced diet of 4200 to 6300 J/d for weeks 17 to 20. Thirty-three of the 36 subjects completed the 20-week program and the 1-year follow-up. Use of the VLCD produced greater decreases in fasting glucose at the end of the 20-week program and at 1-year follow-up and greater long-term reductions in HbA1. The VLCD group also had greater weight losses at week 20, but weight losses from pretreatment to 1-year follow-up were similar in the two treatment groups. The improved glycemic control with the VLCD appeared to be due to increased insulin secretion, but further research is needed to confirm this.", "Forty-nine obese diabetic patients with obese spouses (diabetic or nondiabetic) were randomly assigned to an alone or together condition. Patients in the alone group participated by themselves in a 20-week behavioral weight control program; their spouses attended assessment sessions only. Patients in the together group attended the program with their spouses; both were targeted for weight loss and taught social support strategies. Weight losses of patients treated alone and together did not differ significantly at posttreatment (19.9 vs. 19.1 lb) or 1-year follow-up (11.6 vs. 7.0 lb). However, there was a significant interaction of treatment and gender; women did better when treated with their spouses, whereas men did better when treated alone. A \"family-based\" approach was not effective for these obese Type II diabetic patients as a whole but may be helpful for women.", "Two studies were conducted to determine whether adding exercise to a diet programme promotes weight loss or glycaemic control in Type 2 (non-insulin-dependent) diabetic subjects. In Study 1, 25 subjects were randomly assigned to diet plus moderate exercise or diet plus placebo exercise. All subjects exercised twice a week as a group and once a week on their own; the diet plus moderate exercise group walked a 3-mile route at each session while the diet plus placebo exercise group did very low intensity exercises such as stretching and light calisthenics. All subjects followed a calorie-counting diet and were taught behaviour modification strategies. Weight losses and improvements in glycaemic control did not differ significantly between the two treatment groups at the end of the 10-week treatment or at 1-year follow-up. In Study 2, more extreme conditions were compared: a diet only group and a diet plus exercise group. The diet plus exercise group walked a 3-mile route with the group 3 times/week and once a week on their own, while the diet only group was instructed to maintain their current low level of activity. Both groups received comparable diet and behaviour modification instruction and therapist contacts. The diet plus exercise group had significantly (p less than 0.01) better weight losses than the diet only condition at the end of the 10 week programme (-9.3 kg vs -5.6 kg) and at 1 year follow-up (-7.9 kg vs -3.8 kg).(ABSTRACT TRUNCATED AT 250 WORDS)", "Since most obese patients with type II diabetes are unable to achieve ideal body weight, this study examined whether more modest weight losses would provide a long-term benefit. Type II diabetic patients (N = 114) were treated in a behavioral weight control program and followed up for one year. Weight loss was significantly correlated with improvements in glycosylated hemoglobin values at posttreatment (r = .55) and one year (r = .51). Patients who lost more than 6.9 kg or had more than 5% reduction in body weight had significant improvements in glycosylated hemoglobin values at one year, while patients losing less weight had nonsignificant changes and those gaining weight had significant worsening. Thus, modest weight loss can have a long-term impact on glycemic control. However, the improvement in glycemic control for a given weight loss was greater initially than at one year, suggesting that energy restriction, in addition to weight loss, may contribute to initial improvement. Neither percent overweight nor diabetes treatment affected weight loss.", "1. A prospective randomized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications. 2. During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate, modified-fat (MF) diet showed a similar decrease. 3. Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet. Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens. 4. Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America. A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose.", "The aim of the study was to ascertain the metabolic and dietary determinants of changes in serum lipids during a 15-month diet therapy of obese patients (n = 71, 41 males, 30 females) with recently diagnosed Type 2 (non-insulin-dependent) diabetes. The subjects lost weight and improvement in glycaemic control was observed, but due to variation in individual responses the mean serum total cholesterol or non-HDL cholesterol did not change significantly. The proportion of palmitic acid decreased and that of linoleic acid increased in serum lipids during the study, and serum triglycerides decreased and HDL-cholesterol increased. In univariate analyses, decreased serum triglyceride level was associated with serum triglycerides at baseline, decreases in body mass index, fasting blood glucose and palmitic acid proportion of serum triglycerides, and the intake of saturated fats and dietary fibre, but in multiple regression analyses the determinants for decreased serum triglycerides were high serum triglycerides at baseline and a decreased proportion of palmitic acid in serum triglycerides. In univariate analysis, increased HDL-cholesterol was associated with the baseline HDL-cholesterol, decrease in the triceps/subscapularis ratio and the intake of saturated and mono-unsaturated fatty acids, but none of these variables had an independent contribution to the increase in serum HDL-cholesterol in multiple regression analysis. In conclusion, a reduction of palmitic acid in the serum lipids, which was probably due to reduction of dietary saturated fatty acids, had beneficial effects on serum lipids in obese patients with Type 2 diabetes, independently of weight loss and improvement in glycaemic control.", "Compared weight losses during first and second bouts of a very low calorie diet (VLCD) and examined whether decreased compliance might in part explain the decrease in weight loss during the second bout. Forty-five Type II diabetic patients participated in a year-long behavioral weight-reduction program that incorporated a VLCD (400 to 500 kcal/day) during Weeks 1 to 12 and 28 to 40. Weight losses decreased dramatically from the first to the second VLCD (15.54 vs. 1.42 kg, p less than .0001). There was also markedly diminished adherence as assessed by weeks ketonuric, attendance, and completeness of self-monitoring records. The percentage of weeks subjects were in ketosis dropped from 61% during VLCD 1 to 13% during VLCD 2 (p less than .0001). Similarly, subjects attended significantly fewer treatment meetings during VLCD 2 and self-monitored less during VLCD 2 than during VLCD 1. Weeks ketonuric and initial weight accounted for 63% of the variance in weight loss during VLCD 1 (p less than .0001); weeks ketonuric and attendance predicted weight loss during VLCD 2 (p less than .0001), accounting for 54% of the variance. These results suggest the importance of behavioral factors in explaining poorer performance on a repeated diet.", "To compare the weight losses of black and white patients with NIDDM treated in a year-long behavioral weight loss program.\n Subjects were randomly assigned to a behavioral program that either used a low-calorie diet throughout or included two 12-week periods of a very-low calorie diet (VLCD). Weight, dietary intake, and exercise were measured at 0, 6, and 12 months of treatment, and attendance and self-monitoring records were assessed weekly throughout the year.\n Blacks had smaller weight losses than whites regardless of treatment condition. Overall weight losses (baseline to 1 year) were 7.1 kg in blacks vs 13.9 kg in whites. The differences in overall outcome resulted primarily from greater weight regain in blacks during months 6-12 than in whites. There was a trend for blacks to have poorer attendance than whites during the latter half of the program and for blacks to report smaller changes in calorie intake from baseline to 6 months.\n The results confirm prior studies with nondiabetic patients showing smaller weight losses in blacks than in whites and suggest that these differences may result primarily from faster weight regain in blacks. Further research is needed to more carefully examine the variables that may explain this difference and to develop more effective programs for blacks with NIDDM.", "A recent study found that increases in insulin sensitivity following weight loss and stabilization were strongly related to subsequent weight regain. The present paper analyzed this relationship in two behavioral weight-loss programs. In the first study, 125 nondiabetic subjects were followed over 30 months; weight losses averaged 10 kg at six months, and subjects had regained 8 kg of their weight loss by their 30-month follow-up. Neither fasting insulin levels at six months nor changes in fasting insulin from zero to six months were related to subsequent weight regain. Similarly, insulin levels measured two hours after a 75 g glucose load were unrelated to subsequent weight regain. The second study followed 33 individuals with Type II diabetes, treated with behavior modification, and either a low calorie diet or a very low calorie diet. Weight losses averaged 18 kg at six months, and subjects had regained 10 kg by their 24-month follow-up. The Bergman minimal model was used to assess insulin sensitivity at 6-month intervals. Initial analyses suggested that changes in insulin sensitivity from zero to six months were related to subsequent weight regain, but this effect was strongly influenced by an outlier. After removing this individual, there were no significant relationships between the changes in insulin sensitivity that accompanied weight loss and future weight regain. Likewise, insulin sensitivity at 12 months did not predict weight regain from 12 to 24 months. These data do not support the hypothesis that increases in insulin sensitivity with weight loss are associated with subsequent weight regain.", "To evaluate a year-long behavioral weight control program, used with and without an intermittent very-low-calorie diet (VLCD) in the treatment of type II diabetes mellitus.\n Subjects (n = 93) were randomly assigned to 50-week treatment programs that used either a balanced low-calorie diet (LCD) of 1,000 to 1,000 kilocalories (kcal) per day throughout or included 2 12-week periods of a VLCD of 400 to 500 kcal per day alternating with the balanced LCD. Weight, glycemic control, blood pressure, and lipids were assessed at baseline, at the end of the year-long treatment, and at 2-year follow-up.\n Subjects in the VLCD program lost significantly more weight than did LCD subjects at the end of the 50-week program (14.2 kg versus 10.5 kg; P = 0.057) and remained off diabetes medication longer (P < 0.05). These benefits of the VLCD were due primarily to the first 12 weeks of the diet; the second diet maintained, but did not increase, these effects. Subjects in both groups experienced marked improvements in glycemic control and cardiovascular risk factors over the year-long program, but attendance declined in the latter weeks of treatment and weight was regained. There was also marked recidivism in both groups in the year following treatment.\n The intermittent VLCD improved weight loss and glycemic control, but these effects were quite modest and do not appear to justify the clinical use of an intermittent VLCD. Moreover, lengthening treatment to a full year did not prevent relapse. Thus, further research is needed to develop a successful approach to long-term weight control.", "Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction.\n To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan.\n This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks.\n Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life.\n Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean differences (+/-SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-group P values), respectively, were as follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02); diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, -0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/- 21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/- 0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg; and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly improved for daily and work activities (P < .05) and nutritional health perceptions (P < .05) with the CCNW plan relative to the self-selected group. Overall nutrient intake and compliance were both significantly (P < .001) better with the CCNW plan.\n Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease.", "It has been suggested that much effort expended in teaching diabetic diets is ineffective and wasteful. We have tested a different system by randomly allocating 75 newly diagnosed obese Type 2 diabetic patients to usual 'unstructured' clinic care or to group education by diabetes specialist nurses and a dietitian. Patients allocated to group education attended five 90-min group sessions during the first 6 months. Six months after diagnosis they had lost more weight (median (95% Cl), 7 (5.5-9) vs 2(1-5)kg, p less than 0.002) and were better controlled (HbA1:7.5 (7.0-8.1) vs 9.5 (8.7-10.4)%, p less than 0.001) than those randomized to the usual clinic system. At 1 year (after no further visits) the difference in weight loss was less (5.5 (4-6.5) vs 3 (2-4) kg, p less than 0.05) and diabetic control was similar (HbA1:9.0(8.2-9.8) vs 9.9(8.9-10.9)%. At 1 year only 14(39%) of the education group and 9(23%) of those attending the clinic had a fasting blood glucose less than 7.0 mmol l-1.", "Noncompliance with therapeutic diets remains a major obstacle to achieving improvements in cardiovascular disease (CVD) morbidity and mortality. This study compared dietary compliance and CVD risk factor response to two dietary interventions designed to treat hypertension, dyslipidemia, and diabetes mellitus. In a multicenter trial, 560 adults were randomly assigned to either a self-selected, mixed-food plan (n = 277), or a nutrient-fortified prepared meal plan (n = 283); each was designed to provide 15-20% of energy from fat, 55-60% from carbohydrate, and 15-20% from protein. Nutrient intake was estimated from 3-d food records collected biweekly throughout the 10-wk intervention. Compliance was determined by evaluating the participants' ability to meet specific criteria for energy intake [+/-420 kJ (100 kcal) from the midpoint of the prescribed energy range], fat intake (< 20%, < 25%, or < 30% of energy from total fat), and the National Cholesterol Education Program/American Heart Association Step 1 and 2 diet recommendations. Compliance with energy, fat, and Step 1 and 2 criteria was better in participants who followed the prepared meal plan than in those who followed the self-selected diet (P < 0.0001). Compliant participants in both groups achieved greater reductions in body weight, systolic and diastolic blood pressure, and total and low-density-lipoprotein cholesterol than noncompliant participants (P < 0.05). In general, better endpoint responses were observed with lower fat intakes regardless of group assignment. The prepared meal plan is a simple and effective strategy for meeting the many nutrient recommendations for CVD risk reduction and improving dietary compliance and CVD endpoints.", "In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD).\n Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity.\n Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid.\n IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.", "Non-insulin-dependent diabetes mellitus (NIDDM) is preceded by impaired glucose tolerance (IGT) lasting for years before manifesting as overt hyperglycaemia. Both genetic and environmental factors contribute to the development of IGT and NIDDM. Obesity, physical inactivity and high-fat diet have been found to predict IGT and NIDDM. Therefore, a diet and exercise intervention from diagnosis of NIDDM could improve the treatment outcome and prognosis of patients with NIDDM. Furthermore, because subjects with IGT are at increased risk for diabetes and atherosclerotic vascular disease, it is reasonable to assume that in terms of reducing the incidence and longterm consequences of NIDDM an intervention at this phase is more effective than in overt diabetes. Although the nonpharmacological approach is generally accepted as the first-line treatment of NIDDM its efficacy has often been questioned. Therefore, it is important to carry out long-term controlled studies to find out to what extent lifestyle modification could improve the metabolic control and level of major cardiovascular risk factors known to be associated with poor outcome in NIDDM. This kind of study also gave relevant experience in planning studies aiming at primary prevention of NIDDM. One-year dietary and exercise intervention on newly diagnosed NIDDM patients in Kuopio, Finland resulted in a better metabolic control and a moderate reduction in cardiovascular risk factors as compared to the conventional treatment group. After the second year of follow-up only 12.5% in the intervention group were receiving oral antidiabetic drugs vs. 34.8% in the conventional treatment group. Weight reduction and a reduced use of saturated fats appeared to be the main determinants of successful treatment results. Good aerobic capacity was associated with an increase in HDL cholesterol. A multicentre primary prevention study on IGT patients is continuing in Finland applying the same principles of intervention as used in the study on newly diagnosed NIDDM patients. Pilot results show that glucose tolerance can be improved by lifestyle changes.", "nan", "The treatment of choice for Type II or non-insulin-dependent diabetes mellitus is a behavioral program for the management of weight. However, compliance with this lifelong dietary regimen is often poor. In the current investigation male and female adults with diagnosed Type II diabetes were randomly assigned to either a behavior modification, a cognitive modification, a cognitive-behavior modification, or a control group. Patients were evaluated in terms of weight, percentage of body fat, and glycosylated hemoglobin measures. Men lost significantly more weight than women and subjects in the behavior modification group lost more weight and demonstrated greater decreases in diabetes control than subjects in the cognitive-behavior modification, cognitive, and control groups. A significant interaction indicated that diabetic men may benefit more from behavioral weight reduction programs than diabetic women. Several explanations for these findings are considered.", "To evaluate whether group visits, delivered as routine diabetes care and structured according to a systemic education approach, are more effective than individual consultations in improving metabolic control in non-insulin-treated type 2 diabetes.\n In a randomized controlled clinical trial of 112 patients, 56 patients were allocated to groups of 9 or 10 individuals who participated in group consultations, and 56 patients (considered control subjects) underwent individual visits plus support education. All visits were scheduled every 3 months.\n After 2 years, HbA(1c) levels were lower in patients seen in groups than in control subjects (P < 0.002). Levels of HDL cholesterol had increased in patients seen in groups but had not increased in control subjects (P = 0.045). BMI (P = 0.06) and fasting triglyceride level (P = 0.053) were lower. Patients participating in group visits had improved knowledge of diabetes (P < 0.001) and quality of life (P < 0.001) and experienced more appropriate health behaviors (P < 0.001). Physicians spent less time seeing 9-10 patients as a group rather than individually, but patients had longer interaction with health care providers.\n Group consultations may improve metabolic control in the medium term by inducing more appropriate health behaviors. They are feasible in everyday clinical practice without increasing working hours.", "Metabolic control worsens progressively in Type II (non-insulin-dependent) diabetes mellitus despite intensified pharmacological treatment and lifestyle intervention, when these are implemented on a one-to-one basis. We compared traditional individual diabetes care with a model in which routine follow-up is managed by interactive group visits while individual consultations are reserved for emerging medical problems and yearly checks for complications.\n A randomized controlled clinical trial of 56 patients with non-insulin-treated Type II diabetes managed by systemic group education and 56 control patients managed by individual consultations and education.\n Observation times were 51.2+/-2.1 months for group care and 51.2+/-1.8 for control subjects. Glycated haemoglobin increased in the control group but not in the group of patients ( p<0.001), in whom BMI decreased ( p<0.001) and HDL-cholesterol increased ( p<0.001). Quality of life, knowledge of diabetes and health behaviours improved with group care ( p<0.001, all) and worsened among the control patients ( p=0.004 to p<0.001). Dosage of hypoglycaemic agents decreased ( p<0.001) and retinopathy progressed less ( p<0.009) among the group care patients than the control subjects. Diastolic blood pressure ( p<0.001) and relative cardiovascular risk ( p<0.05) decreased from baseline in group patients and control patients alike. Over the study period, group care required 196 min and 756.54 US dollars per patient, compared with 150 min and 665.77 US dollars for the control patients, resulting in an additional 2.12 US dollars spent per point gained in the quality of life score.\n Group care by systemic education is feasible in an ordinary diabetes clinic and cost-effective in preventing the deterioration of metabolic control and quality of life in Type II diabetes without increasing pharmacological treatment.", "The aim of this randomized trial was to compare the effects of a behavioral intervention focusing on either calorie restriction alone or calorie plus fat restriction on weight loss and changes in lipids and glycemic control in individuals with non-insulin-dependent diabetes mellitus (NIDDM) or a family history of diabetes.\n We recruited 44 obese women with NIDDM and 46 obese women with a family history of NIDDM and randomly assigned these subjects to calorie restriction (CAL) or to calorie plus fat restriction (CAL + FAT). All subjects participated in a 16-week behavioral weight loss program, with training in diet, exercise, and behavior modification. Subjects assigned to the CAL condition were given a 1,000-1,500 kcal/day goal and self-monitored calories consumed. Subjects assigned to the CAL+FAT condition had the same calorie goal, but were also given a fat goal (grams of fat/day), to produce a diet with < 20% of calories from fat; this group monitored both calories and fat grams.\n Among NIDDM subjects, weight loss of the subjects in the CAL+FAT condition was significantly greater than subjects in the CAL condition (7.7 vs. 4.6 kg) and the CAL+FAT condition group also maintained their weight loss better at the 1-year follow-up (5.2 vs. 1.0 kg). Significant decreases in glucose, high-density lipoprotein (HDL) cholesterol, and total cholesterol were seen after 16 weeks of treatment among NIDDM subjects; these changes were similar in CAL and CAL+FAT groups, but a greater proportion of subjects in CAL condition required oral hypoglycemic medication. At the 1-year follow-up, all parameters had returned to baseline. No significant differences in weight loss or physiological changes were seen between CAL and CAL+FAT conditions in subjects with a family history of diabetes.\n These results suggest that using the combination of calorie and fat restriction may help promote weight loss in obese NIDDM patients. No other long-term benefits of this regimen were observed.", "In a prospective study 150 newly detected maturity onset-diabetics were randomized in 2 biostatistically comparable groups and underwent a treatment of different intensity. While the patients of the control group were treated according to the routine method used up to now in the dispensary for diabetics, in the intervention group an intensifying of the therapy took place, taking particular into consideration the body weight as well as the carbohydrate and fat metabolism. The decrease of body weight achieved by dietary intensive care proved to be the decisive factor for the tendency towards normalisation of glucose tolerance, hyperlipoproteinaemia and IRI-secretion, which could be registered in the intervention group after 2 years of observation. Following the preceding strong phase of diet, by Biguanides and Clofibrate a further significant improvement of the carbohydrate and fat metabolism could not be achieved. The decisive reserve in the treatment of obese maturity onset-diabetes could be seen in a permanent and continuous reduction of body weight. The results of this treatment depend highly on an intensive education as well as on frequent control of the patients' metabolism and their cooperation.", "This study sought to determine whether weight loss would alter body fat distribution in obese men and women with type II diabetes. Subjects were 60 women and 33 men who participated in a year-long weight loss program. Weight losses of women and men, respectively, averaged 13.4 kg and 16.8 kg at six months and 11.2 kg and 13.1 kg at one year. WHR decreased significantly in both genders: for women, WHR decreased from 0.95 at baseline to 0.93 at six months and 0.94 at one year; for men WHR decreased from 0.99 at baseline to 0.96 at six months and 0.96 at one year. Subjects with greater upper body obesity at baseline did not lose more weight than subjects with less upper body obesity, but they did have greater reductions in WHR at six months in both genders and at one year in men. The magnitude of WHR reduction was strongly related to the amount of weight lost in men, but was not related to weight loss in women. Improvements in fasting glucose, fasting insulin, and HbA1 were significantly related to weight loss, but not to reductions in WHR. Thus, participation in a weight loss program had beneficial effects on body fat distribution in patients with type II diabetes, but these changes in WHR were not independently associated with improvements in glycemic control.", "The aim of this study was to assess the effects of a 1-year intensified diet and exercise education regimen on habitual physical activity and aerobic capacity in middle-aged, obese patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus. In addition, we analysed whether the level and the changes in physical activity and aerobic capacity are related to the metabolic control of diabetes. After a 3-month basic education programme, 78 patients (45 men, 33 women) were randomly placed in an intervention or conventionally treated group. The intervention group received intensified diet education and continuous encouragement to increase physical activity which was monitored using exercise records and questionnaires. Aerobic capacity was assessed by measuring oxygen uptake at anaerobic threshold and at peak exercise. The proportion of patients with regular recreational exercise increased from 24% to 38% in the intervention men (0.10 less than p less than 0.20), remained at 54% in the conventionally treated men, increased from 53% to 70% in the intervention women (0.10 less than p less than 0.20) and from 31% to 50% (0.10 less than p less than 0.20) in the conventionally treated women. No measurable improvement was found in oxygen uptake in any of the groups. When the groups were combined, HbA1c showed an inverse correlation with oxygen uptake at anaerobic threshold (r = 0.27, p less than 0.01) and maximum oxygen uptake (r = 0.28, p less than 0.01) at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate whether plasma fibrinogen concentration is correlated with the level of physical activity and aerobic power in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM).\n We studied 78 middle-aged (54 +/- 6 years, mean +/- SD), obese (body mass index [BMI] 32+/- 5 kg/m2) patients (45 men and 33 women) before and after a 12-month treatment period consisting of either conventional treatment given by community health centers or intensified dietary and exercise education given by a university outpatient clinic. Plasma fibrinogen concentration was measured by using a coagulometer. Physical activity was assessed by a questionnaire, and the patients were classified into a sedentary group or moderately or intensively exercising groups. Aerobic power (maximum oxygen uptake [VO2max], anaerobic threshold [VO2at]) was measured by direct breath-by-breath technique.\n At baseline, the sedentary patients had higher fibrinogen concentration than those with moderate or high physical activities (3.8 +/- 0.8 vs. 3.3 +/- 0.7 g/l, P < 0.01). Both VO2max and VO2at (ml.min-1.kg-1) showed an inverse linear correlation with fibrinogen (r = -0.38, P < or = 0.001, and r = -0.29, P < 0.01, respectively). In the stepwise multiple regression analysis, BMI, VO2 (ml/min), and smoking were the only significant independent factors explaining 23% of the variance in fibrinogen concentration. In sedentary patients, poor glycemic control was related with high fibrinogen concentration. During the follow-up period, patients maintained, on the average, good to moderate glycemic control. The originally sedentary group showed a decrease in fibrinogen concentration (to 3.3 +/- 0.7 g/l, P < or = 0.001) that reached the same level that the physically more active groups had at baseline. This change was associated with improved glycemic control, but not with any of the other assessed factors, including fatty acid composition of serum lipids reflecting dietary intake of fats.\n In addition to BMI and smoking, low reported physical activity and low aerobic power are independently associated with high plasma fibrinogen concentration in newly diagnosed NIDDM." ]

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[ "Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study.", "The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo.", "Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.", "Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.", "Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy.", "Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.", "The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial.", "Glutathione in the prevention of cisplatin induced toxicities. A prospectively randomized pilot trial in patients with head and neck cancer and non small cell lung cancer.", "Randomized study of a short course of weekly cisplatin with or without amifostine in advanced head and neck cancer. EORTC Head and Neck Cooperative Group.", "A randomized, multicenter, double-blind, placebo-controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian cancer.", "Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity.", "A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results.", "Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities.", "N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data.", "Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy.", "Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer.", "Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer.", "Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial.", "Protective effect of amifostine against toxicity of paclitaxel and carboplatin in non-small cell lung cancer: a single center randomized study." ]

[ "Whether the administration of calcium (Ca) and magnesium (Mg) can reduce oxaliplatin-related neurotoxicity remains controversial. In addition, little is known about the effects of Ca/Mg on the blood level of platinum or objective tumor progression.\n Patients receiving modified FOLFOX6 for metastatic colorectal cancer were double-blinded and randomized to receive additional treatment with Ca/Mg or placebo before and after the administration of oxaliplatin. The plasma and ultrafiltrable concentrations of platinum during the first and fifth cycles of treatment were determined using inductively coupled plasma spectrometry.\n Patients were randomized to receive Ca/Mg (Ca/Mg group, n = 17) or placebo (placebo group, n = 16) before and after the administration of oxaliplatin (85 mg/m(2)). The incidence of neurotoxicity after six cycles was not significantly different between the two groups. Blood concentrations of platinum at each time and the area under the curve were also not significantly different between the two groups. Furthermore, the response rate (RR) and disease control rate (DCR) did not differ significantly between the two groups (Ca/Mg group: RR 36%, DCR 73%. Placebo group: RR 40%, DCR 70%, P > 0.99). The median progression-free survival time was 9.2 months in the Ca/Mg group and 8.1 months in the control group; these survival times were not significantly different (P = 0.56).\n These data are insufficient to conclude with any certainty that the administration of Ca/Mg is not neuroprotective; however, the administration of Ca/Mg may not have any influence on antitumor activity and the blood concentration profile of platinum in patients receiving oxaliplatin-based chemotherapy.", "Peripheral neuropathy is an important and disabling side-effect of cisplatin treatment. A new drug, Org 2766, has been found to prevent this neuropathy up to 1 month after treatment. A group of 18 patients with ovarian cancer, who participated in an earlier randomized study with placebo or Org 2766, together with cisplatin and cyclophophamide, were thereafter prospectively followed up to 2 years after discontinuation of treatment to monitor the development of neurological signs and symptoms and vibration perception threshold (VPT). Exploratory, descriptive data analysis shows that between 1 and 4 months after the last cycle the average sum score for neurological signs and symptoms and VPT had deteriorated compared with 1 month after treatment. Thereafter a gradual but incomplete improvement was seen between 4-12 and 12-24 months after treatment. These changes were seen in all patients regardless of previous treatment with Org 2766 or placebo, but deterioration was less pronounced in patients previously treated with Org 2766. These results suggests that treatment with Org 2766 to prevent a cisplatin-induced neuropathy should possibly be continued up to 4 months after the last cycle of cisplatin.", "A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy.\n Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles.\n One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups.\n We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.", "We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity.\n Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment.\n At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH.\n This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.", "The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy.\n Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E.\n Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone.\n Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.", "We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity.\n Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m(2) over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m(2)), eight (oxaliplatin dose, 800 mg/m(2)), and 12 (oxaliplatin dose, 1,200 mg/m(2)) cycles of treatment.\n At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P =.003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P =.004). The neurophysiologic investigations (sural sensory nerve conduction) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm. The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing no reduction in activity of oxaliplatin.\n This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.", "The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.", "Glutathione has been shown to be an effective chemoprotector against cisplatin-induced side effects in patients with ovarian cancer. In view of this fact, we performed a randomized clinical pilot-trial in the management of other solid tumors in order to compare application of Glutathione to intensive hydration in patients undergoing chemotherapy with a regimen including cisplatin.\n Twenty patients suffering from advanced non small cell lung cancer (n = 6) or head- and neck cancer (n = 14) were enrolled in the study. All patients received 80 mg/m2 cisplatin along with etoposide or 5-fluorouracil every 4 weeks. Patients randomized to application of Glutathione (n = 11) received 5 g of Glutathione immediately before application of cisplatin followed by 2000 ml of normal saline. Patients in the control group (n = 9) received 2000 ml electrolyte infusion before and 2000 ml of normal saline with forced diuresis after cisplatin.\n The intensity of hematologic toxicity was significantly less pronounced in patients treated with Glutathione than in the control group (hemoglobin: 10.7 vs 9.5 mg% respectively, p = 0.039; white blood cell count 3.3 vs 2.2 x 103/microliter respectively, p = 0.004; platelets 167 vs 95 x 103/microliter respectively, p = 0.02), whereas in terms of non-hematologic toxicity no difference was observed. Objective remission occurred in 6 out of 11 evaluable patients from the group receiving Glutathione (55%; complete remission: 9%; partial remission: 46%), and in 4 out of 8 evaluable patients from the control group (partial remission: 50%). However, there was no statistical difference in terms of response and overall survival (13.5 months vs. 10.5 months) between the two groups.\n Application of Cisplatin and Glutathione seems to be safe and feasible and the antitumoral efficacy of cisplatin is apparently not impaired by the concomitant use of Glutathione in patients with solid tumors.", "Cisplatin is one of the most active cytotoxic agents available for the treatment of patients with head and neck cancer. In a previous phase II study with weekly administration of cisplatin, a response rate of 51% was achieved. However, only in a minority of the patients the planned high dose intensity of 80 mg/m2/week could be reached because of toxicity, mainly thrombocytopenia and ototoxicity. Amifostine is a cytoprotective drug that can diminish the toxicity of alkylating agents and platinum compounds. Therefore the effect of amifostine on toxicity and activity of weekly cisplatin was investigated in a randomized study.\n Patients with locally advanced, recurrent or metastatic head and neck cancer were eligible. Patients were randomized to weekly cisplatin 70 mg/m2 for six cycles preceded by amifostine 740 mg/m2, or cisplatin only. Cisplatin was administered in hypertonic saline (3% NaCl) as a one-hour infusion; amifostine was administered as a 15-minute infusion directly before the administration of cisplatin.\n Seventy-four patients were entered in the study. The median number of cisplatin administrations was 6 (range 2-6), equal in both arms. In both treatment arms the median dose intensity of cisplatin achieved was the planned 70 mg/m2/week. In the cisplatin only arm 6 out of 206 cycles were complicated by thrombocytopenia grade 3 or 4 versus 1 of 184 cycles in the amifostine arm (P = 0.035). Hypomagnesaemia grade 2 + 3 was significantly less observed in the amifostine arm (P = 0.04). Neurotoxicity analyzed by serial vibration perception thresholds (VPT) showed a diminished incidence of subclinical neurotoxicity in the amifostine arm (P = 0.03). No protective effect on renal and ototoxicity could be shown. Hypotension was the main side effect of amifostine but only of relevance in one patient. The antitumor activity of cisplatin was preserved as 63% of the evaluable patients in the amifostine arm responded compared to 50% of the evaluable patients in the cisplatin alone arm.\n Our study indicated that in combination with weekly administered cisplatin amifostine reduced the risk of thrombocytopenia, hypomagnesemia as well as subclinical neurotoxicity, but did not result in a higher dose intensity of cisplatin. Addition of amifostine did not compromise the antitumor effect of cisplatin.", "The objective was to evaluate the efficacy of Org 2766 (a hexapeptide analogue of ACTH) in the prevention or delay of cisplatin-induced neuropathy during chemotherapy in women with ovarian cancer as measured by vibration perception threshold (VPT).\n In this randomized, multicenter, double-blind, placebo-controlled study, 196 women with ovarian cancer were treated with cisplatin 75-100 mg/m2, cyclophosphamide 600-1000 mg/m2 plus placebo or two dose levels of Org 2766. The cisplatin-induced neuropathies were monitored by determining the VPT with the Vibratron II. VPT was determined for both the most sensitive great toe and the index finger on a monthly basis during treatment and months 1, 2, and 3 postchemotherapy. Once the blind was broken, it was found that 174 women (59 in placebo, 58 in 2 mg, and 57 in 4 mg) had enough data to allow evaluation.\n Over the course of follow-up, the VPT was found to increase. This is consistent with the development of cisplatin-induced peripheral neuropathies. The baseline VPT for the index finger was less than that of the great toe (0.65 vs 2.13), but the percentage change in VPT was the same for both (percentage increase in VPT of about 350%). When the VPTs are compared according to the dose of Org 2766 given, there appears to be no difference in the rate of change or degree of neuropathies that developed in these women receiving cisplatin and cyclophosphamide.\n The development of cisplatin-induced neuropathies is confirmed by measurement of the VPT. The rate of development of neuropathies seems to accelerate after the sixth course of cisplatin. When the development of neuropathies is evaluated on the basis of Org 2766 dosage, it is found that there is no difference in the rate or degree of neuropathies seen. Instead of providing protection from and delay of onset of peripheral neuropathies caused by cisplatin, these results suggest that the administration of Org 2766 appears to cause an increase in the rate of change and degree of neuropathies (P > 0.05).\n Copyright 1997 Academic Press.", "Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) regimen has become the standard adjuvant treatment for colorectal cancer. However, the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy. Many strategies have been proposed in order to manage the neurotoxicity, but their effect on antitumoral efficacy is still unclear. In this study, we investigated the effect of reduced glutathione administration on neurotoxicity, oxaliplatin pharmacokinetics, and platinum-DNA (Pt-DNA) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen. Twenty-seven patients were randomized to receive GSH 1500 mg/m or saline solution before oxaliplatin infusion. Evaluation of neurotoxicity, pharmacokinetics of plasmatic total and ultrafiltered Pt, and determination of Pt-DNA adduct formation on white blood cells was performed during the 5th, 9th, and 12th cycles. At the end of all cycles of therapy, the patients in the GSH arm showed a statistically significant reduction of neurotoxicity (P=0.0037) compared with the placebo arm. There were no significant differences in the main pharmacokinetic parameters between the two arms except a lower area under the plasma concentration-time curve and a smaller apparent steady-state volume of distribution (Vss) when GSH was coadministered. This difference can be explained by the natural function of GSH in the detoxification of oxaliplatin and by its ability to remove the Pt bound to plasma proteins. The determination of Pt-DNA adduct formation shows no statistically significant differences between the two arms. In conclusion, this study indicates that coadministration of GSH is an effective strategy to reduce the oxaliplatin-induced neurotoxicity without impairing neither the pharmacokinetics of oxaliplatin, nor the Pt-DNA adduct formation.", "A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN).\n A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score.\n The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation.\n Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.", "Diethyldithiocarbamate (DDTC) blocks cisplatin-induced toxicities in animal models without inhibiting antitumor effects. DDTC chemoprotection was tested in a randomized, multicenter, double-blind comparison versus placebo (PB) in patients with lung or ovarian cancer. Primary end points were nephrotoxicity, ototoxicity, neuropathy, and completion of therapy.\n Between April 1990 and February 1992, 221 patients were registered with small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), or ovarian cancer. Cisplatin (100 mg/m2) and cyclophosphamide (in ovarian cancer) or etoposide (in lung cancer) were administered with either DDTC (1.6 g/m2 over 4 hours) or PB intravenously, every 4 weeks for a planned six cycles.\n At an interim safety analysis, data were available for 195 patients from the combined lung and ovarian cancer populations (PB, 99 patients; DDTC, 96 patients). Withdrawal for chemotherapy-induced toxicities occurred in 9% of PB-treated patients and 23% of DDTC-treated patients (P = .008). The mean cisplatin delivered dose-intensity (DDI) was 23 mg/m2/wk on both arms. However, the mean cisplatin cumulative dose delivered (CDD) was 379 mg/m2 on the PB arm, compared with 247 mg/m2 on the DDTC arm (P = .0001). At the time of interim analysis, 28% of PB-treated patients had completed all six cycles of therapy, compared with only 6% of DDTC-treated patients (P < .001). Although, clinical hearing loss, neuropathy, emesis, and myelosuppression were equivalent in the two treatment arms, DDTC-treated patients had more nephrotoxicity as determined by changes in serum creatinine concentration. Toxicities related to DDTC infusion included transient hypertension, flushing, and hyperglycemia. DDTC did not compromise response rates in either tumor type.\n This study did not demonstrate a significant chemoprotective effect against cisplatin-induced toxicities with the DDTC dose schedule tested. Patients who received DDTC received lower cumulative doses of cisplatin, but were more likely to be withdrawn from treatment early due to chemotherapy-related toxicities.", "Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3-4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.", "We conducted a randomized, open-label, controlled trial to assess the efficacy of oxcarbazepine for prophylaxis against oxaliplatin-induced peripheral neuropathy (OxIN). Thirty-two patients with colon cancer received 12 courses of the FOLFOX-4 regimen and were randomly assigned to receive oxcarbazepine (600 mg BID) or chemotherapy without oxcarbazepine. The incidence of OxIN was strikingly decreased in patients receiving oxcarbazepine (31.2% vs 75%). Oxcarbazepine may prevent OxIN symptoms. Further larger placebo-controlled trials are warranted to confirm our results.", "Serious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer.\n Two hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival.\n Pretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. Hematologic toxicity consisted of grade 4 neutropenia associated with fever and/or infection that required antibiotic therapy (P = .005), days in hospital (P = .019), and days on antibiotics (P = .031). Platinum-specific toxicities consisted of protracted serum creatinine elevations (P = 0.004), > or = 40% reduction from baseline in creatinine clearance (P = .001), and severity of neurologic toxicity (P = .029). Twenty-four percent of CP patients compared with 9% of amifostine plus CP patients discontinued therapy because of protocol-specified toxicity (P = .002). Pathologic tumor response rates were 37% with amifostine and 28% in controls, with comparable median survival times of 31 months. Amifostine was generally well tolerated; the principal side effects were emesis and a transient decrease in blood pressure.\n Pretreatment with amifostine reduces the cumulative hematologic, renal, and neurologic toxicities associated with the CP regimen, with no reduction in antitumor efficacy.", "In a randomized, double-blind, placebo-controlled study, we assessed the efficacy of an ACTH(4-9) analogue, Org 2766, in the prevention of cisplatin neuropathy in 55 women with ovarian cancer. The analogue was given subcutaneously in a dose of 0.25 mg (low dose) or 1 mg (high dose) per square meter of body-surface area before and after treatment with cisplatin and cyclophosphamide (75 and 750 mg per square meter every three weeks). The threshold of vibration perception was used as the principal measure of neurotoxicity. After four cycles of chemotherapy, the mean (+/- SEM) threshold value for vibration perception in the placebo group increased from 0.67 +/- 0.12 to 1.61 +/- 0.43 microns of skin displacement (P less than 0.0001). In the high-dose treatment group, there was no increase in the threshold value after four cycles (from 0.54 +/- 0.12 to 0.50 +/- 0.06 micron). After six cycles of chemotherapy, the threshold value was 5.87 +/- 1.97 microns in the placebo group (more than an eight-fold increase from base line), as compared with 0.88 +/- 0.17 micron (less than a twofold increase) in the high-dose treatment group (P less than 0.005). In the high-dose group, fewer neurologic signs and symptoms were recorded than in the placebo group. With the lower dose of the analogue, these protective effects were less prominent. No side effects were seen after treatment with Org 2766. The rates of clinical response to chemotherapy were similar in all groups. These results suggest that Org 2766 can prevent or attenuate cisplatin neuropathy without adversely affecting the cytotoxic effect of the drug.", "Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin.\n One hundred fifty-one patients with ovarian cancer (stage I-IV) were evaluated in a clinical trial of cisplatin (CDDP) +/- glutathione (GSH). The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity.\n When considering the proportion of patients receiving six courses of CDDP at any dose, GSH produced a significant advantage over control--58% versus 39%, (P = 0.04). For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control--74% versus 62% (P = 0.006). Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an indication of overall activity, these patients were statistically significantly more able to undertake housekeeping and shopping. Clinically assessed response to treatment demonstrated a trend towards a better outcome in the GSH group (73% versus 62%) but this was not statistically significant (P = 0.25).\n The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved.", "In this study we determined the protective role of amifostine against the side effects of the combination of paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC).\n Chemo-naive patients with NSCLC were eligible. Thirty-eight patients were randomized to receive paclitaxel 175 mg/m2 and carboplatin AUC = 6 with amifostine 910 mg/m2 (group B) or chemotherapy alone (group A). The occurrences of hematologic, neurologic, cardiologic toxicities, and ototoxicity were evaluated.\n All patients completed the six scheduled cycles of therapy. A total of 114 cycles of chemotherapy was given in both groups. Neutropenia grade 3-4 was observed in 11 cycles (9.6%) in group A and 19 cycles (16.6%) in group B (p = 0.16). Paresthesia grade 1 or 2 was observed in 18 of 19 patients of group A and in 8 of 19 patients of group B, following the sixth cycle of chemotherapy (p = 0.018). Two patients of group B and nine patients of group A suffered from sensory motor impairment grade 2 (p = 0.029). There was no clinical evidence in any patient for deterioration in cardiac function. Asymptomatic and transient sinus bradycardia or ventricular premature beats developed in four patients. None of the patients reported vertigo, tinnitus, or hearing loss.\n The addition of the amifostine to the combination of paclitaxel and carboplatin may prevent or reduce the incidence of neurotoxicity in the treatment of NSCLC. Amifostine does not appear to have a preventive role in neutropenia." ]

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[ "Ketorolac versus acetaminophen-codeine in the emergency department treatment of acute low back pain.", "Tizanidine and ibuprofen in acute low-back pain: results of a double-blind multicentre study in general practice.", "Comparative study of Biarison and Voltaren in acute lumbar pain and lumbo-ischialgia.", "Medical treatment of acute low back pain. Diflunisal compared with indomethacin in acute lumbago.", "Trial of an anti-inflammatory agent (indomethacin) in low back pain with and without radicular involvement.", "An open study of diflunisal, conservative and manipulative therapy in the management of acute mechanical low back pain.", "Parenteral dipyrone versus diclofenac and placebo in patients with acute lumbago or sciatic pain: randomized observer-blind multicenter study.", "Oral meloxicam is effective in acute sciatica: two randomised, double-blind trials versus placebo or diclofenac.", "A controlled clinical trial of sustained-action dextropropoxyphene hydrochloride.", "Comparison of diflunisal and acetaminophen with codeine in the treatment of initial or recurrent acute low back strain.", "A comparative trial of azapropazone and ketoprofen in the treatment of acute backache.", "Continuous low-level heat wrap therapy provides more efficacy than Ibuprofen and acetaminophen for acute low back pain.", "Double-blind controlled trial comparing oxyphenbutazone and indomethacin in the treatment of acute low back pain.", "[Dexketoprofen-trometamol and tramadol in acute lumbago].", "Clinical evaluation of ketoprofen (Orudis) in lumbago - a double-blind comparison with diclofenac sodium.", "The effect of phenylbutazone on patients with acute lumbago-sciatica. A double blind trial.", "A comparison of the short-term effects of ibuprofen and diclofenac in spondylosis.", "Overexertional lumbar and thoracic back pain among recruits: a prospective study of risk factors and treatment regimens.", "[Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes].", "[Intramuscular etofenamate in the treatment of acute lumbago. Effectiveness and tolerance in comparison with intramuscular diclofenac-Na].", "Multicentre double-blind comparison of piroxicam and indomethacin in the treatment of lumbar diseases.", "A randomized double-blind pilot study comparing Doloteffin and Vioxx in the treatment of low back pain.", "Medicines of choice in low back pain.", "Effects of valdecoxib in the treatment of chronic low back pain: results of a randomized, placebo-controlled trial.", "Efficacy and safety of rofecoxib in patients with chronic low back pain: results from two 4-week, randomized, placebo-controlled, parallel-group, double-blind trials.", "[Reduced diclofenac administration by B vitamins: results of a randomized double-blind study with reduced daily doses of diclofenac (75 mg diclofenac versus 75 mg diclofenac plus B vitamins) in acute lumbar vertebral syndromes].", "Treatment of acute low back pain with the COX-2-selective anti-inflammatory drug nimesulide: results of a randomized, double-blind comparative trial versus ibuprofen.", "Treatment of chronic low back pain with etoricoxib, a new cyclo-oxygenase-2 selective inhibitor: improvement in pain and disability--a randomized, placebo-controlled, 3-month trial.", "A clinical trial with indomethacin (indomee(R)) in low back pain and sciatica.", "Analgesic efficacy and safety of lornoxicam quick-release formulation compared with diclofenac potassium: randomised, double-blind trial in acute low back pain.", "A double-blind, multicentre, randomised clinical trial comparing the efficacy and tolerability of aceclofenac with diclofenac resinate in patients with acute low back pain.", "Efficacy of etoricoxib 60 mg/day and diclofenac 150 mg/day in reduction of pain and disability in patients with chronic low back pain: results of a 4-week, multinational, randomized, double-blind study.", "Naproxen sodium, diflunisal, and placebo in the treatment of chronic back pain.", "A double blind, placebo controlled study of piroxicam in the management of acute musculoskeletal disorders.", "Acute low-back pain. An objective analysis of conservative therapy.", "Relief of acute low back pain with diclofenac-K 12.5 mg tablets: a flexible dose, ibuprofen 200 mg and placebo-controlled clinical trial.", "Flurbiprofen for the treatment of soft tissue trauma.", "Cyclobenzaprine and naproxen versus naproxen alone in the treatment of acute low back pain and muscle spasm.", "[Therapy of lumbar sciatica. A comparative clinical study of a corticoid-free monosubstance and a corticoid-containing combination drug].", "Topical analgesics, indomethacin plaster and diclofenac emulgel for low back pain: a parallel study.", "The natural course of acute sciatica with nerve root symptoms in a double-blind placebo-controlled trial evaluating the effect of piroxicam.", "Mefenamic acid, chlormezanone-paracetamol, ethoheptazine-aspirin-meprobamate: a comparative study in acute low back pain.", "Treatment of acute low-back pain with piroxicam: results of a double-blind placebo-controlled trial.", "Comparison of diflunisal and naproxen in the management of acute low back strain.", "[Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study].", "Objective functional assessment of the efficacy of tenoxicam in the treatment of acute low back pain. A double-blind placebo-controlled study.", "Acute back pain and spasm. A controlled multicenter trial of combined analgesic and antispasm agents.", "The efficacy and tolerability of an 8-day administration of intravenous and oral meloxicam: a comparison with intramuscular and oral diclofenac in patients with acute lumbago. German Meloxicam Ampoule Study Group.", "Double-blind parallel study of piroxicam versus indomethacin in the treatment of low back pain.", "Valdecoxib is as efficacious as diclofenac in the treatment of acute low back pain.", "Double-blind parallel study of meptazinol versus diflunisal in the treatment of lumbago." ]

[ "Acute low back pain is a common problem in the emergency department (ED). Effective management of acute pain enhances early rehabilitation and recovery. Given the importance of inflammatory mediators in pain generation and the adverse effects associated with opioids, it is logical to expect that a non-opioid agent with antiinflammatory and analgesic properties would provide excellent analgesia with fewer adverse effects. This double-blind, randomized, multicenter clinical trial, performed in six university and community hospital EDs, compares the analgesic efficacy and adverse effects of ketorolac to those of acetaminophen-codeine in ED patients with acute musculoskeletal low back pain. Our hypothesis was that ketorolac would provide superior analgesia with fewer adverse effects. One hundred twenty-three patients with acute low back pain were randomized to receive ketorolac (KET, N = 63) or acetaminophen-codeine (ACOD, N = 60). Most (79%) were males, and the mean age was 34.5 years. After baseline clinical assessment, patients were treated with ketorolac (10 mg every 4 to 6 h as needed, up to four daily doses) or acetaminophen-codeine (600 mg-60 mg, respectively, every 4 to 6 h as needed, up to six daily doses) and followed for one week. Pain intensity was assessed on visual analogue and categorical scales. Functional capacity, overall pain relief, and overall medication rating were assessed on categorical scales. Adverse events were documented. Primary outcomes included: 1) Pain intensity differences, based on visual analogue scores, for the 0 to 6 h treatment phase. 2) Incidence of adverse events. Secondary outcomes included analgesic efficacy, functional capacity, and overall subjective drug evaluation at one week. Both drugs provided substantial pain relief, with maximal effect 2.2 h after oral dosing. There were no significant differences in analgesic efficacy, functional capacity, or overall pain relief between the two groups. Sixteen patients (10 KET vs. 6 ACOD, NS) withdrew prematurely because of drug inefficacy. Patients in the ACOD group reported significantly more adverse drug events and serious adverse drug events. Seven patients--all in the ACOD group--withdrew from the study because of adverse drug events. Based on comparable efficacy and a superior adverse event profile, ketorolac was preferable to acetaminophen with codeine for the treatment of acute low back pain in the ED.", "This study reports on 105 patients with acute low-back pain given tizanidine (4 mg three times daily) plus ibuprofen (400 mg three times daily) or placebo plus ibuprofen (400 mg three times daily). Patients assessed their pain using visual analogue scales in a daily diary and the doctor assessed their condition at baseline and on days 3 and 7. Both groups were treated effectively, but earlier improvement occurred in patients given tizanidine/ibuprofen, particularly regarding pain at night and at rest. Doctors assessed the helpfulness of treatment: tizanidine/ibuprofen was significantly better than placebo/ibuprofen at day 3 (P = 0.05). Significant differences between treatments in favour of tizanidine/ibuprofen occurred in patients with moderate and severe pain at night (P less than 0.05), at rest (P less than 0.05) and those with moderate or severe sciatica (P less than 0.05). Significantly more patients given placebo/ibuprofen had gastro-intestinal side-effects compared with tizanidine/ibuprofen (P = 0.002). This supports previous work in animals showing that tizanidine mediates gastric mucosal protection against anti-inflammatory drugs. More patients given tizanidine/ibuprofen suffered drowsiness and other central nervous system effects (P = 0.025). In patients with severe acute low-back pain, however, some sedation and bed rest is advantageous. This study shows that tizanidine/ibuprofen is more effective in the treatment of moderate or severe acute low-back pain than placebo and ibuprofen alone.", "nan", "Diflunisal and indomethacin were compared in patients with acute lumbago in a double-blind prospective clinical trial. The dosage of diflunisal was 500 mg twice daily (d-group) and the dosage of indomethacin 50 mg three times daily (i-group). Out of 133 patients, 66 were in the d-group and 67 in the i-group. They were followed up for a week. In addition to the patient's own daily evaluation of pain and functional disability, control visits were performed by the investigators on days 0, 3 and 7. Both of the test drugs were effective in the dosages used. Patients' pain was decreased, functional disability was improved and patients' subjective evaluation of treatment efficacy was very similar to that of the investigators. There were no differences as to the treatment efficacy, but reports of side-effects were slightly less (p less than 0.05) in the d-group than in the i-group. If patients who had no side-effects were compared, the efficacy of diflunisal was better than indomethacin (p less than 0.05). It can be said that indomethacin was essentially as effective as diflunisal, but at the expense of an increased frequency of side-effects. In the d-group two patients (3%) and in i-group six patients (9%) discontinued the therapy because of side-effects. In acute lumbago rapid relief of pain and other harmful symptoms hastens improvement. For such indications the choice of drug therapy in general practice should be based in particular on considerations of safety and lack of potential side-effects in addition to efficacy.", "A short-term double-blind sequential trial of indomethacin against placebo in the treatment of low back pain, with and without nerve root pain such as sciatica, showed that indomethacin was significantly more effective than placebo in the group with nerve root pain. On the other hand, no difference was found between the treatments in the patients with uncomplicated low back pain. This difference may result from an effect of indomethacin on the inflammatory process around the nerve root which has been shown to be present when this is compressed.", "One hundred and twelve patients with acute mechanical low back pain were randomly divided into three treatment groups. All patients received ergonomic advice and then either a non-steroidal anti-inflammatory drug or conservative or manipulative types of physiotherapy. Serial assessments of pain and spinal mobility showed similar response rates in all three treatment groups and no significant difference between therapies. The overall improvement ratings, time off work, and economic cost favoured the group treated with the nonsteroidal anti-inflammatory drug, but this group had a better range of spinal flexion at the onset so firm conclusions regarding the preferred management of these patients in general practice cannot be drawn. Treatment failures occurred in all groups highlighting the need for a variety of therapeutic approaches in managing the patient with low back pain.", "Two hundred and sixty patients with lumbago or sciatic pain participated in a multicenter observer-blind randomized trial to compare the efficacy and tolerability of dipyrone 2.5 g, diclofenac 75 mg, and placebo administered as an intramuscular injection once daily for the duration of one to two days. The effectiveness of the test treatments in relieving sciatic pain was measured by a visual analog scale (VAS) before and 30 minutes, 1, 2, 3, 6 and 24 hours after each injection. In addition, the patient's general well-being was measured on a 5-point rating scale on day 0, 1 and 2. At the end of the trial, the patients evaluated the overall efficacy of the study drugs on a 5-point rating scale. Minimal finger-toe distance was measured every day of the trial. Pain intensity on VAS (primary endpoint) showed a significantly greater reduction with dipyrone than with diclofenac or placebo between 1 and 6 hours after application (p < 0.01) and at the end of the trial (after 48 hours). Improvement in general well-being and minimal finger-toe distance was greatest in the dipyrone group. 59% of the patients with dipyrone assessed the overall efficacy as \"excellent\" or \"very good\", compared with 30% with diclofenac, and 18% with placebo. Adverse reactions were reported in only 7 patients (3%), 4 (5%) in the dipyrone, 1 (1%) in the diclofenac, and 2 (2%) in the placebo group.", "Two randomised, double-blind, double-dummy trials evaluated the efficacy and tolerability of meloxicam compared with placebo or diclofenac in patients with acute sciatica.\n 1021 patients with acute sciatica.\n In the first study, 532 patients received meloxicam 7.5 mg, meloxicam 15 mg, or placebo for 7 days. The second study randomised 489 patients to meloxicam 7.5 mg, meloxicam 15 mg, or diclofenac 150 mg for 14 days.\n Meloxicam 7.5 mg and 15 mg significantly improved overall pain between baseline and day 7 (p < 0.05) compared with placebo. Furthermore, both meloxicam doses showed similar improvements on all primary and secondary efficacy endpoints compared with diclofenac 150 mg. No significant differences in tolerability were observed between any of the treatment groups in either study.\n Meloxicam (7.5 mg or 15 mg) was well tolerated and was more effective than placebo, and as effective as diclofenac, in acute sciatica.", "nan", "Effective pain relief and patient tolerance and acceptance are essential in outpatient management of mild to moderate pain of acute low back strain. This study evaluated the efficacy, tolerability, and acceptability of diflunisal and acetaminophen with codeine in patients with mild to moderate pain after an initial or recurrent acute low back strain. Both drugs demonstrated equipotent analgesic efficacy; however, diflunisal was superior to acetaminophen with codeine for patient tolerability and acceptability. The results demonstrated that the study drugs were effective in treating mild to moderate pain caused by acute low back strain in an ambulatory care setting.", "A double-blind trial of azapropazone (300 mg. 4-times daily) and ketoprofen (50 mg. 4-times daily) was carried out in 50 patients with acute backache sufficiently severe to necessitate hospital admission. Of 39 patients who completed the full 3-weeks' study period, 18 preferred azapropazone therapy, 10 preferred ketoprofen, and 11 showed either preference for the intermediate placebo period or no preference at all. Ten patients suffered from sufficiently severe side-effects with ketoprofen to necessitate their withdrawal from the trial. There were no similar episodes of withdrawal occurring during the azapropazone period.", "A prospective, randomized, single (investigator) blind, comparative efficacy trial was conducted.\n To compare the efficacy of continuous low-level heat wrap therapy (40 C, 8 hours/day) with that of ibuprofen (1200 mg/day) and acetaminophen (4000 mg/day) in subjects with acute nonspecific low back pain.\n The efficacy of topical heat methods, as compared with oral analgesic treatment of low back pain, has not been established.\n Subjects (n = 371) were randomly assigned to heat wrap (n = 113), acetaminophen (n = 113), or ibuprofen (n = 106) for efficacy evaluation, or to oral placebo (n = 20) or unheated back wrap (n = 19) for blinding. Outcome measures included pain relief, muscle stiffness, lateral trunk flexibility, and disability. Efficacy was measured over two treatment days and two follow-up days.\n Day 1 pain relief for the heat wrap (mean, 2) was higher than for ibuprofen (mean, 1.51; P = 0.0007) or acetaminophen (mean, 1.32; P = 0.0001). Extended mean pain relief (Days 3 to 4) for the heat wrap (mean, 2.61) also was higher than for ibuprofen (mean, 1.68; P = 0.0001) or acetaminophen (mean, 1.95; P = 0.0009). Lateral trunk flexibility was improved with the heat wrap (mean change, 4.28 cm) during treatment (P </= 0.009 vs acetaminophen [mean change, 2.93 cm], P </= 0.001 vs ibuprofen [mean change, 2.51 cm]). The results were similar on Day 4. Day 1 reduction in muscle stiffness with the heat wrap (mean, 16.3) was greater than with acetaminophen (mean, 10.5; P = 0.001). Disability was reduced with the heat wrap (mean, 4.9), as compared with ibuprofen (mean, 2.7; P = 0.01) and acetaminophen (mean, 2.9; P = 0.0007), on Day 4. None of the adverse events were serious. The highest rate (10.4%) was reported in the ibuprofen group.\n Continuous low-level heat wrap therapy was superior to both acetaminophen and ibuprofen for treating low back pain.", "nan", "BACKGROUND, METHOD: The analgesic efficacy and tolerability of dexketoprofen-trometamol (DKPT) was compared with tramadolhydrochloride (TRAM) in a multicentre, randomised, double-blind, clinical trial in 192 Patients with acute low back pain. The initial pain at rest and on movement should be at least 50 mm on a 100 mm visual analogue scale. The daily dose during the 7 days' treatment was 50 mg TRAM t.i.d. (n = 95) or 25 mg DKPT t.i.d. (n = 97). The patients were allowed to take additional Paracetamol up to 4 x 500 mg per day as rescue medication.\n From the 4th day of treatment pain on movement decreased significantly (p = 0.044) in the DKPT-group in comparison with the TRAM-group. The nocturnal pain decreased during the treatments with a difference in therapies of 22.9% in favour of DKPT. Within the DKPT-group the patients required additional Paracetamol more often only during the 1st day of treatment whereas the patients of the TRAM-group required the additional rescue medication mainly during the first 3 days of treatment. This difference was statistically significant (p = 0.011). Under DKPT treatment patients experienced significantly less adverse events (with an at least \"possible\" causal relationship; p = 0.026). This can be explained by central nervous disturbances that occurred only in the TRAM group. The distribution of gastro-intestinal disorders was identical in both treatment groups.\n With this results DKPT in comparison with TRAM also showed to be a strong analgesic drug with a better risk-benefit relation due to its better tolerability.", "nan", "nan", "In this controlled, single-blind parallel group study, the effect of ibuprofen 1200 mg daily was compared with diclofenac 75 mg daily. Thirty patients entered the study, randomized into two groups, each group receiving one tablet three times daily for two weeks. A one-week wash-out period (i.e. a drug-free period during which only physiotherapy was given), preceded and followed the treatment on active drug. Assessments were made by the same clinician throughout who was unaware of the treatment of individual patients. Statistically significant improvement was shown by patients receiving ibuprofen for the degree of pain relief at rest and improvement was also shown for the degree of pain at rest and during exercise, for pain relief during exercise and for spinal flexion. Patients who received diclofenac showed statistically significant improvement for forward flexion, together with improvement for the degree of pain on exercise. Side-effects were very few.", "A total of 395 male infantry recruits were evaluated in a prospective study of possible risk factors for overexertional back pain and the efficacy of drug treatment regimens for this syndrome. Recruits were classified into subgroups of lumbar or thoracic, and paraspinal or spinous process pain. Recruits were divided into three treatment groups: Ibuprofen, Paracetamol, and no drug treatment. Of the recruits, 18% were diagnosed as having overexertional back pain during the course of 14 weeks of training. By multivariate analysis low body mass index was found to be a risk factor for overexertional lumbar pain (p = 0.005) and increased lumbar lordosis a risk factor for overexertional thoracic pain (p = 0.005). Of recruits with overexertional back pain, 65% were asymptomatic by the end of basic training. There was no statistically significant difference between cure rates according to treatment groups.", "The use of nonsteroidal anti-inflammatory drugs (NSAID) such as diclofenac for treatment of degenerative rheumatic disorders of the lumbar spine is of great significance in orthopedic practice. Clinical studies have shown that concomitant treatment with vitamins B1, B6, B12 and diclofenac provides more efficient pain relief than treatment using diclofenac alone. This study was undertaken in order to determine whether the duration of treatment with diclofenac for lower back pain can be shortened by adding B-vitamins to the therapeutic regimen. From September through December of 1986, 256 patients participated in a multicenter, controlled, randomized double-blind trial which compared the clinical efficacy of diclofenac (50 mg) with a combined therapy of diclofenac (50 mg) and vitamins B1, B6, and B12 (thiamine nitrate, pyridoxine hydrochloride, and cyanocobalamine, resp.; in dosages of 50 mg, 50 mg, and 0.25 mg, resp.). Patients were treated with 3 X 1 capsule daily for a maximum of two weeks, having the option to terminate participation in the trial after 1 week in the event of total pain relief. The data of 238 patients were able to be included in the evaluation. 29 patients opted to discontinue therapy due to remission on symptoms. Nineteen (65.6%) of these patients belonged to the combined therapy group, the other 10 (34.4%) having taken diclofenac alone; this difference is statistically significant (p less than 0.05). An important aspect in the evaluation of therapy was the patient response regarding the improvement of painful symptoms which, in addition to their subjective feedback, was reflected in the test results of the \"Hoppe Pain Questionnaire (HPQ).\" All parameters used as a measure of pain relief indicated superior results with the B-vitamin supplemented therapy when compared with results obtained with diclofenac alone. Moreover, after 3 days of therapy the \"sensory\" pain factor \"sharpness\" improved significantly. Undesirable side-effects were documented with 39 patients, 14 of them having discontinued therapy for this reason. No statistically significant difference could be determined within this group with regard to therapy. The study results document the positive influence of B-vitamins on painful symptoms and indicate that less NSAID is needed for pain relief when combined with B-vitamins.", "In a controlled multi-center single-blind study, the relative efficacy and tolerance of i.m. injectable preparations of etofenamat(e) and diclofenac sodium were investigated in 96 patients with acute lumbago. Treatment resulted in obvious improvement in function and reduction in pain, no statistical difference being found between the two drugs. In 43% of the patients treated with etofenamat(e) and 27% of those receiving diclofenac, the final medical report indicated very good therapeutic results. Under etofenamat(e) i.m. therapy, no side effects occurred, and in no case did treatment have to be discontinued. Under diclofenac, two patients experienced adverse reactions, one allergic exanthema, and the other itching and a sensation of heat. A further patient experienced no improvement after the first injection and discontinued treatment.", "In a 2-week, double-blind, parallel, multicenter study, piroxicam (20 mg once-daily) and indomethacin (25 mg three times daily) were compared in the treatment of painful lumbar disorders. A total of 230 patients were evaluated, 116 who received piroxicam and 114 who received indomethacin. While both drugs were highly effective in relieving symptoms, numerical superiority was evident for piroxicam in most efficacy parameters. The difference between treatments was most obvious at the end of the first week, when a greater percentage of patients receiving piroxicam was rated as 'very much improved'. No serious adverse reactions or clinical laboratory abnormalities were noted for either drug, although fewer gastrointestinal side effects were observed with piroxicam.", "This randomized, double-dummy, double-blind pilot study of acutely exacerbated low back pain was aimed to inform a definitive comparison between Doloteffin, a proprietary extract of Harpagophytum, and rofecoxib, a selective inhibitor of cyclo-oxygenase-2 (COX-2).\n Forty-four patients (phyto-anti-inflammatory drug-PAID-group) received a daily dose of Doloteffin containing, inter alia, 60 mg of harpagoside for 6 weeks and 44 (non-steroidal anti-inflammatory drug-NSAID-group) received 12.5 mg/day of rofecoxib. All were allowed rescue medication of up to 400 mg/day of tramadol. Several outcome measures were examined at various intervals to obtain estimates of effect size and variability that might be used to decide the most suitable principal outcome measure and corresponding numbers required for a definitive study.\n Forty-three PAID and 36 NSAID patients completed the study. Ten PAID and 5 NSAID patients reported no pain without rescue medication for at least 5 days of the 6th week of treatment. Eighteen PAID and 12 NSAID patients had more than a 50% reduction in the week's average of their pain scores between the 1st and 6th weeks. The mean percentage decrease from baseline in the pain component of the Arhus Index was 23 (S.D. 52) in PAID and 26 (S.D. 43) in NSAID. The corresponding measures for the overall Arhus Index were 11 (31) and 16 (24) and, for the Health Assessment Questionnaire, 7 (8) and 6 (7). Tramadol was used by 21 PAID patients and 13 NSAID patients. Fourteen patients in each group experienced 39 adverse effects, of which 28 (13 in PAID) were judged to some degree attributable to the study medications.\n Though no significant intergroup differences were demonstrable, large numbers will be needed to show equivalence.", "The marketed formulations of 6 analgesic preparations were compared in the treatment of patients suffering from acute exacerbations of low back pain using a crossover trial of balanced incomplete block design. Sixty out-patients with symptoms resulting from a mechanical or degenerative condition were each prescribed 3 drugs which were administered consecutively for 1 week each. The medications (and daily dosages) were coded as A --aspirin (3600 mg), B --dextropropoxyphene plus paracetamol (260 mg plus 2600 mg), C --indomethacin (150 mg), D --mefenamic acid (1500 mg), E --paracetamol (4000 mg), and F --phenylbutazone (300 mg). Daily pain scores were significantly lower (p less than 0.05) during treatment D than during treatments E and B, and significantly lower (p less than 0.05) during treatment A than during treatment B. There were large and significant differences between treatments in the percentages of recommended doses acceptable to the patients and in the number of defaults from the prescribed regimens. The patients chose F and D significantly more (p less than 0.05) often than A. Overall, there were consistently superior performances by mefenamic acid and phenylbutazone with little to choose between the two.", "Valdecoxib, a cyclooxygenase (COX)-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea. Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition.\n The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain.\n This 4-week, prospective, randomized, double-blind placebo-controlled, parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada. Patients aged > or =18 years with chronic low back pain in flare were enrolled. Patients were randomized to receive valdecoxib 40-mg/d or placebo tablets, once daily for 4 weeks. Patients rated low back pain intensity on a visual analog scale and completed the Roland-Morris Disability Questionnaire and the modified Brief Pain Inventory-Short Form (mBPI-SF) at each visit.\n Two hundred ninety-three patients were enrolled. The valdecoxib group comprised 148 patients (81 women, 67 men; mean [SD] age, 48.6 [13.3] years; mean [SD] body weight, 86.6 [20.9] kg), and the placebo group included 145 patients (85 women, 60 men; mean [SD] age, 48.7 [12.6] years; mean [SD] body weight, 85.6 [19.9] kg). Of the enrolled patients, 249 completed the study: 134 patients (91%) who received valdecoxib and 115 patients (79%) who received placebo. No statistically significant differences in patient baseline characteristics were noted between treatment groups, except in response to 1 mBPI-SF question; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group (P = 0.048). Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment (all, P < 0.001 vs placebo). Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment (all, P < or = 0.014 vs placebo). Improvements in mean Roland-Morris Disability Questionnaire score with valdecoxib were significantly greater than with placebo at each assessment (all, P < or = 0.003). Although the overall incidence of adverse events (AEs) was significantly higher among patients receiving valdecoxib than those receiving placebo (35.1% vs 24.1%, respectively; P = 0.042), no significant differences were found between groups for the incidence of any individual AE. Most AEs (89% [77/87 total events]) were mild or moderate in severity.\n In this study of patients with chronic low back pain, valdecoxib 40 mg/d provided rapid relief (within 1 week) and consistent relief (over 4 weeks). In addition, significant improvement in function and decreased disability were found with valdecoxib compared with placebo.", "Two replicate, 4-week, randomized, double-blind, placebo-controlled, trials of rofecoxib 25 and 50 mg versus placebo for chronic low back pain.\n To determine the efficacy and safety of two doses of rofecoxib compared to placebo in the treatment of chronic low back pain.\n Although nonsteroidal anti-inflammatory drugs are commonly prescribed for chronic low back pain, their efficacy is unproven and toxicity can be serious. These studies evaluated the efficacy and tolerability of rofecoxib, a selective COX-2 inhibitor, in the treatment of chronic low back pain.\n Patients with chronic low back pain were randomized 1:1:1 to rofecoxib 25 mg, 50 mg, or placebo once daily. Primary endpoint: Low Back Pain Intensity. Secondary endpoints: Pain Bothersomeness, Global Assessments of Response to Therapy, Global Assessment of Disease Status, Roland-Morris Disability Questionnaire, SF-12 Health Survey, Use of Rescue Acetaminophen, and Discontinuations Due to Lack of Efficacy.\n Combining both studies, 690 patients were randomized to placebo (N = 228), rofecoxib 25 mg (N = 233), or rofecoxib 50 mg (N = 229). Mean (+/- SD) age was 53.4 (+/- 12.9) years, pain duration 12.1 (+/- 11.8) years, 62.3% female. Both rofecoxib groups improved significantly. Mean differences from placebo in pain intensity were -13.50 mm, -13.81 mm (25, 50 mg doses) respectively (P < 0.001). Both regimens were superior to placebo in eight of nine secondary endpoints. Fifty mg provided no advantage over 25 mg. Both rofecoxib regimens were well tolerated, although 25 mg had a slightly better safety profile.\n Rofecoxib significantly reduced chronic low back pain in adults and was well tolerated.", "Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice. The therapeutic effect of NSAIDs is not subject to doubt in this connection. But considering that the application of NSAIDs is frequently associated with side effects, a reduction of dosage would be to the patient's benefit. Clinical studies have shown that concomitant treatment with vitamins B1, B6, B12 and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs. This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac (75 mg daily) is used. 123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days. There was the option to terminate therapy in the trial after 3-4 days in the case of total pain relief. 45 patients could stop the treatment due to remission of symptoms. 30 patients belonged to the combination therapy group, the other 15 took diclofenac alone; this difference is statistically significant (p less than 0.05). All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination, too. The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage.", "A prospective, randomized double-blind comparative trial.\n To evaluate the efficacy and tolerability of nimesulide, a cyclooxygenase (COX)-2-selective anti-inflammatory agent versus ibuprofen in patients with acute lumbosacral back pain.\n Nonsteroidal anti-inflammatory drugs (NSAIDs) have been more effective than placebo in patients with uncomplicated acute low back pain in previous randomized controlled trials. The efficacy and tolerability of a new COX-2-selective anti-inflammatory drug have not yet been established.\n One hundred four patients aged 18-65 years with acute low back pain were enrolled. The patients were randomly allocated either to oral nimesulide (100 mg twice daily for 10 days) or oral ibuprofen (600 mg three times daily for 10 days). Outcome measures on a visual analog scale were an average of the pain intensity and the pain relief, stiffness in the back, functional status, and the results of physical examinations. All side effects were recorded at each visit.\n With both study therapies, there was a clear improvement in all measured parameters of the pain and back function parameters measured from the third day of treatment onward. The patients' capacity for daily tasks, showed improvement in both groups (P < 0. 001), but a statistically significant difference was found between the two groups in favor of the nimesulide group (P < 0.05) after 10 days. Nimesulide was more effective than ibuprofen in improved lateral bending measurements (P = 0.026). Nimesulide and ibuprofen provided similar degrees of improvement in the modified Schober tests and in the pain intensity and back stiffness scores. More gastrointestinal side effects were reported with ibuprofen than nimesulide, and the comparison showed a trend (P = 0.067). Ten side effects occurred in the nimesulide group in 7 (13%) patients and 13 in the ibuprofen group in 11 (21%) patients.\n The results confirmed that the COX-2-selective inhibitor nimesulide is an effective and well-tolerated agent for use in general practices to treat acute low back pain. The incidence of gastrointestinal side effects seems to be lower with nimesulide than with ibuprofen.", "We evaluated etoricoxib, a novel COX-2-specific inhibitor, in 319 patients with chronic low back pain (LBP) in this double-blind, placebo-controlled trial. Patients were randomized to a 60 mg dose (n = 103) or 90 mg dose (n = 107) of etoricoxib, or placebo (n = 109), daily for 12 weeks. The primary endpoint was low back pain intensity scale (Visual Analog Scale of 0- to 100-mm) time-weighted average change from baseline over 4 weeks. Other endpoints included evaluation over 3 months of low back pain intensity scale, Roland-Morris Disability Questionnaire (RMDQ), low back pain bothersomeness scale, patient- and investigator-global assessments, Patient Health Survey (MOS SF-12), rescue acetaminophen use, and discontinuation due to lack of efficacy. Etoricoxib provided significant improvement from baseline versus placebo in pain intensity (4 weeks: 12.9 mm and 10.3 mm for 60-mg and 90-mg doses, P <.001 for each; 12 weeks: 10.5 mm and 7.5 mm for 60-mg and 90-mg doses, P =.001 and.018, respectively). Etoricoxib at either dose led to significant improvement in other endpoints, including RMDQ scores, bothersomeness scores and global assessments. Etoricoxib given once daily provided significant relief of symptoms, and disability associated with chronic LBP that was observed 1 week after initiating therapy, was maximal at 4 weeks, and was maintained over 3 months.", "nan", "NSAIDs are widely used for patients presenting with low back pain. A quick-release formulation of lornoxicam, a potent NSAID from the chemical class of oxicams, offers a faster onset of pain relief compared with the standard tablet formulation.\n Time to onset of pain relief with lornoxicam was compared with the quick-release formulation of diclofenac potassium in acute low back pain in a randomised, double-blind, multicentre study. 220 patients received either lornoxicam 24 mg or diclofenac potassium 150 mg on day 1 followed by lornoxicam 8 mg twice daily or diclofenac potassium 50 mg twice daily for 5 days. Efficacy outcomes included time to onset of pain relief, as measured by the stopwatch method (primary outcome), pain intensity, pain relief, rescue medication, ability to perform daily activities and global evaluation of the study medication.\n The time to onset of pain relief ratios between diclofenac potassium/lornoxicam was 1.03 (95% CI 0.91, 1.26) and 1.05 (95% CI 0.93, 1.29) in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively, demonstrating the non-inferiority of lornoxicam (defined by lower limits of the 95% CIs >0.80). Time to onset of pain relief was shorter with lornoxicam (30 minutes) compared with diclofenac potassium (36 minutes). The difference was not statistically significant (ITT analysis). A higher magnitude of analgesic effect associated with better global evaluation of the study medication for lornoxicam was also demonstrated. The drugs were equally well tolerated.\n Lornoxicam administered as a quick-release formulation was shown to be non-inferior to the equivalent formulation of diclofenac potassium in terms of onset of pain relief and more effective on most of the major standard efficacy outcomes.", "The efficacy and tolerability of aceclofenac was compared with diclofenac resinate in a double-blind, multicentre randomised study in patients with acute low back pain suffering from degenerative spinal disorders. The study included 227 patients randomised to receive either aceclofenac 2 x 100 mg daily or diclofenac resinate 2 x 75 mg daily for up to 10 days. The primary objective was to demonstrate the clinical non-inferiority of the analgesic efficacy of aceclofenac compared with diclofenac resinate, as assessed by changes from baseline in the visual analogue scale (0-100 mm) pain score, at rest and at visit 3 (final visit on day's 8-10). Secondary objectives included the time to early cure (resolution of pain) and global assessment of tolerability. Mean change in pain score at rest, and as visit 3, compared with baseline, was 61.6 mm (SD 24.5) for the aceclofenac group ( n = 100) and 57.3 mm (SD 22.8) for the diclofenac resinate group ( n = 105) in the per-protocol population. Similar changes were observed in the intention-to-treat population. Between-group differences of 4.5 mm and 5.5 mm for the per-protocol and intention-to-treat populations, respectively, demonstrated clinical non-inferiority of aceclofenac compared with diclofenac resinate. Furthermore, there was evidence for superiority of aceclofenac over diclofenac resinate in terms of statistical significance, as the one-sided 97.5% confidence interval was above -10 mm and 0 mm. In the intention-to treat population, a total of six aceclofenac-treated patients discontinued their medication owing to early cure, compared with only one patient receiving diclofenac resinate. Seventeen aceclofenac- (14.9%), and 18 diclofenac resinate-treated patients (15.9%) reported at least one adverse event. However, the total number of adverse events reported was lower in patients receiving aceclofenac (22 versus 31 in the diclofenac resinate group). In conclusion, non-inferiority of the analgesic efficacy of aceclofenac compared with diclofenac resinate was demonstrated in patients with localised, uncomplicated acute lumbosacral pain. For the reduction in pain levels from baseline there was also evidence for superiority of aceclofenac compared with diclofenac resinate in terms of statistical significance, although this difference was not considered clinically relevant. The results also showed a trend towards a better safety and tolerability profile of aceclofenac over diclofenac resinate from a clinical point of view.", "The efficacy and safety of etoricoxib 60 mg/day in patients with established chronic low back pain (CLBP) were compared with those of diclofenac 150 mg/day in a 4-week, multicentre, randomized, double-blind, parallel-group trial. Four hundred and forty-six adult patients with CLBP (Quebec Task Force on Spinal Disorders Class 1 or 2) and with worsening pain upon discontinuation of pre-study analgesic medication were enrolled in the study. The study primary efficacy endpoint was change from baseline in Low Back Pain Intensity Scale (LBP-IS) score over the 4-week treatment period. Secondary and other efficacy endpoints included: changes in Roland and Morris Disability Questionnaire (RMDQ), Patient Global Assessment of Response to Therapy (PGART) and Low Back Pain Bothersomeness Scale (LBP-BS) scores. Early efficacy was assessed using PGART and LBP-IS scores 4 h after the first dose on the mornings of Days 1, 2 and 3. The overall safety and tolerability of etoricoxib 60 mg/day during 4 weeks of treatment were also assessed.\n The least-squares mean time-weighted change from baseline LBP-IS score over 4 weeks was -32.94 mm (95% CI -36.25, -29.63) for etoricoxib, indicating substantial efficacy in relief of pain. The treatment difference for the primary outcome was 2.51 mm (95% CI -1.50, 6.51), fulfilling the prespecified equivalence criterion of 95% confidence interval wholly within +/- 10 mm. Etoricoxib improved all secondary and other efficacy outcomes. There were no statistically significant between-group differences in the proportion of patients with one or more clinical adverse events (AEs) (etoricoxib 35%, diclofenac 39%), or the proportion of patients who discontinued due to AEs (etoricoxib 7%, diclofenac 5%).\n The results of this study confirm that, for adult patients with CLBP, etoricoxib 60 mg once daily over 4 weeks is effective for relief of pain and improvement of physical function and comparable to high-dose diclofenac 150 mg daily.", "Thirty-seven patients with chronic back pain were entered into a randomised, 3-way, double-blind, cross-over comparison of naproxen sodium 550 mg twice daily, diflunisal 500 mg twice daily, and placebo. Each treatment was given for 14 days after a preadmission wash-out week during which only paracetamol was allowed. Patients were assessed on admission and at the end of each treatment with respect to global pain, night pain, pain on movement, and pain on standing. Both visual analogue scales and simple descriptive scales were used to measure pain. Side effects were elicited by a nonleading question. Both methods of pain measurement gave similar results and were highly correlated. Naproxen sodium was superior to placebo in relieving global pain and depending on the method of measurement, in relieving night pain and pain on movement. Diflunisal showed no significant differences from placebo. Side effects were similar on all 3 treatments. The final preference of the patients was significantly in favour of the active treatments.", "General Practitioners from the United Kingdom produced data on 1,282 patients with acute soft tissue injury treated with either piroxicam (Feldene) or matching placebo for a period of up to two weeks. The dosage of piroxicam was 40 mg for the first 2 days and 20 mg daily thereafter. Clinical assessment included pain, swelling, limitation of active and passive movement and overall assessment of efficacy and toleration. Piroxicam was significantly better than placebo in improving patient signs and symptoms, and in its overall efficacy (P less than 0.001); 87% of piroxicam treated patients had excellent or good responses, compared to 53% of placebo treated patients. On analysis of four of the most commonly occurring diagnoses (injuries of ankle, knee, shoulder, back) patients with moderate or severe pain showed a significant improvement on treatment with piroxicam. Physicians' overall assessment of toleration showed no evidence of differences between treatments. Over 90% of patients in both treatment groups had good or excellent toleration. Withdrawals due to side effects were 3% and 2.5% respectively for piroxicam and placebo treated patients.", "The roles of bedrest, antiinflammatory medication, and analgesic medication in the treatment of acute back strain were objectively analyzed to determine whether they have a measurable effect on the return of patients to full daily activities as well as on the relief of pain. Two hundred patients were studied prospectively. Each patient had the diagnosis of acute back strain, which was defined as nonradiating low-back pain. The results of the patient's neurologic examination, straight leg raising test, and lumbosacral spine roentgenograms had to be within normal limits for the patient to be included in the study. The results showed that bedrest, as compared with ambulation, will decrease the amount of time lost from work by 50%. Bedrest will also decrease the amount of discomfort by 60%. Analgesic medication, when combined with bedrest, will further decrease the amount of pain incurred, particularly when used in the first three days of the healing process. However, analgesic medication will not allow a more prompt return to work. Antiinflammatory medication, when added to bedrest in the treatment of lumbago, does not provide an advantage over bedrest alone.", "To assess efficacy and safety of diclofenac-K 12.5 mg tablets in the treatment of acute low back pain (low back pain).\n A multiple dose, double-blind, double-dummy, randomized, placebo-controlled, parallel group trial compared diclofenac-K (12.5 mg; n = 124) with ibuprofen (200 mg; n = 122) and placebo (n = 126) in patients with moderate-to-severe acute low back pain. The treatment consisted of an initial dose of 2 tablets followed by 1 or 2 tablets every 4-6 hours as needed (maximum 6 tablets/day) for 7 days. The primary efficacy outcome for the initial dose was TOTPAR-3, the summed total pain relief over the first 3 hours. Secondary initial dose outcomes included TOTPAR-6, summed pain intensity differences SPID-3 and SPID-6, time to rescue medication or remedicate, and the End of First Dose global efficacy assessment. The primary efficacy outcome for the flexible multiple dosing regimen was the End of Study global efficacy assessment. Secondary outcomes for multiple dosing included time to rescue medication over the entire study, the End of Day global efficacy assessments (daily over Days 1-7), pain intensity differences on the VAS measured at Visit 2 and 3, and change in Eifel algofunctional index. Safety/tolerability was assessed by recording adverse events.\n Diclofenac-K 12.5 mg demonstrated superiority vs placebo on the primary efficacy parameter and almost all secondary initial dose outcomes. With respect to the initial dose, diclofenac-K 12.5 mg was also significantly superior to ibuprofen 200 mg on SPID-3. Ibuprofen 200 mg was superior to placebo only on the End of First Dose global efficacy assessment. The flexible multiple dosing regimens of diclofenac-K and ibuprofen were both significantly superior to placebo on the End of Study global efficacy assessment, time to rescue medication over the entire study period, the End of Day global efficacy assessment on Days 1-2, pain intensity difference on the VAS at Visit 3 and the Eifel algofunctional index at Visit 3 (also at Visit 2 in diclofenac-K 12.5 mg group). Both active treatments were as well tolerated as placebo.\n The flexible multiple dosing regimen of diclofenac-K 12.5 mg (initial dose of 2 tablets followed by 1-2 tablets every 4-6 hours, max. 75 mg/day) is an effective and safe treatment of acute low back pain.", "The use of flurbiprofen as an analgesic and anti-inflammatory agent in patients with soft tissue trauma induced by sports injuries, lumbar disk syndrome, or surgery was considered in three clinical trials. In the first study, soft tissue injuries to the lower limb in 51 professional soccer players were treated for six days with 150 mg of flurbiprofen per day or 3.6 g of aspirin per day. The second study compared three weeks of treatment with daily doses of 200 mg of flurbiprofen and 4 g of acetaminophen in 50 patients with acute low back pain. In the third study, 100 postoperative patients were given 400 mg of flurbiprofen per day or 4 g of acetaminophen per day for seven days following total or partial meniscectomy. In all of these trials, flurbiprofen showed excellent analgesic efficacy in reducing pain and swelling, and enhanced the recovery of patients with soft tissue trauma.", "Two groups of 20 patients each, with mild to moderate acute low back pain with associated muscle spasm of ten days' duration or less, were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a randomized, 14-day open-label trial. Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful, musculoskeletal conditions. The clinical characteristics of each study group, including the number of worker's compensation patients, were comparable. Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine (P less than 0.05). There were trends toward faster resolution of functional deficits and pain with combined therapy. Combination therapy was associated with more side effects, due primarily to drowsiness from the cyclobenzaprine. The results of this study demonstrated that patients with muscle spasm associated with acute low back strain benefited from the use of combination therapy consisting of a nonsteroidal anti-inflammatory agent (naproxen) and a muscle relaxant (cyclobenzaprine).", "nan", "nan", "To study the natural history of acute sciatica, 208 patients with obvious symptoms and signs of a lumbar radiculopathy (L5 and S1) were examined within 14 days of onset. A concomitant double-blind investigation of the effect of the nonsteroidal anti-inflammatory drug piroxicam was performed. The results measured by visual analog scale and Roland's functional tests showed a satisfactory improvement throughout the 4 weeks of observation. The piroxicam-treated group had same results as the control group. Based on questionnaires at months 3 and 12 approximately 30% of the patients still complained about back trouble and 19.5% were out of work after 1 year. Four patients underwent surgery during this period.", "nan", "Twenty-seven investigators participated in a double-blind, parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain. Therapy commenced within 48 hours of the injury and continued for 7 days. The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter. After 3 days of therapy, piroxicam patients showed a statistically greater amount of pain relief in the lying (P less than 0.001), sitting (P less than 0.01), and standing (P less than 0.01) positions, but after 7 days the difference between treatments was no longer significant. After 1 week's therapy, however, the requirement for additional analgesic was significantly lower in the piroxicam group (P less than 0.05), and more piroxicam than placebo patients (42 versus 28) had returned to work (P less than 0.05). Toleration was excellent in most patients, with only 13% of the piroxicam and 17% of the placebo group reporting adverse effects of mainly mild or moderate severity. The profile of the adverse effects was similar for both treatments. Piroxicam can provide effective relief of acute low-back pain with good toleration; it should be considered for use in the initial treatment of this condition.", "Fifty-six patients entered into an open-label, randomized study to compare the efficacy and tolerability of diflunisal and naproxen in the treatment of mild to moderate pain associated with acute low back strain. Thirty-three patients completed the two-week study. No patients withdrew because of side effects, and both drugs were well tolerated. Results showed that diflunisal was more effective than naproxen (81% versus 41%) in relieving pain. Of the 16 patients taking diflunisal, 13 rated its efficacy as very good or excellent; six (35%) of 17 patients taking naproxen rated their drug similarly. Overall, diflunisal rated slightly better in efficacy and tolerability and in improving limitation of function and motion. In addition, diflunisal has a longer duration of action and thus requires less frequent dosing than naproxen.", "Several clinical trials have shown that the duration of treatment of painful vertebral syndromes can be shortened by using a combination of vitamins B1, B6, B12 and diclofenac instead of diclofenac. In addition, a more efficient pain relief could be achieved by the combination therapy. In order to confirm these results, we compared the clinical efficacy of diclofenac (25 mg) and a combination preparation with diclofenac (25 mg) plus vitamins B1 (thiamine nitrate 50 mg), B6 (pyridoxine hydrochloride 50 mg) and B12 (cyanocobalamin 0.25 mg) in a multicentric randomized double-blind study including 418 patients. All patients received 3 x 2 capsules daily for a maximum of 2 weeks. In case of total pain relief, therapy should be discontinued after one week. Data of 376 patients could be evaluated. 53 out of 184 patients receiving the combination and 48 out of 192 patients treated with diclofenac alone could stop therapy due to sufficient pain relief after one week. The evaluation of the \"Hoppe Pain Questionnaire\" and the data concerning pain intensity also revealed better results for the combination preparation. The differences in favour of the B-vitamin-diclofenac-combination were statistically significant in patients with severe pain at the beginning of therapy. Considering undesirable side-effects (symptoms in 70 out of 418 patients) there were no significant differences between the two medications. This clinical trial provides further evidence that the combination therapy with diclofenac plus B-vitamins is more effective than diclofenac alone for the treatment of painful vertebral syndromes.", "The efficacy of an NSAID (tenoxicam) in the treatment of acute low back pain (LBP) was assessed in a double blind controlled study by using an objective functional evaluation. Seventy-three patients consulting for acute LBP were randomized into two groups: Group I was treated with tenoxicam for 14 days and Group II was given a placebo. Trunk function was measured with a computerized isoinertial dynamometric trunk testing device (Isostation B200). Isometric and dynamic torques, range of motion and movement velocities were measured before treatment and after 14 days. Clinical evaluation was realized by the patient on a pain visual analogue scale (VAS) on days 1, 8 and 15 and by the investigator on a five-point scale on days 8 and 15. The functional evaluation showed significant differences in favour of the tenoxicam treatment for velocity and extension isometric torque. VAS and investigator evaluations showed a significant difference in favour of tenoxicam on day 8 but no difference on day 15. This study shows that the use of tenoxicam in acute LBP is of interest. Tenoxicam has an effect on pain during the first part of the treatment and may help to restore full function even if the symptoms have disappeared.", "A double-blind, 18-center, balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients. They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain. Global results over the 7 to 10 days of observations revealed a clinically and statistically significant superiority of the combined therapy by Day 4 (P = 0.006) and almost all patients recovered within a week to 10 days. A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems.", "In this controlled, randomized, parallel and open multicentre study, the efficacy and tolerability of a regimen comprising intravenous (i.v.) meloxicam followed by oral therapy was compared with a standard regimen of intramuscular (i.m.) diclofenac followed by oral dosing in patients with acute lumbago. Of a total of 183 patients, 92 were randomized to receive meloxicam 15 mg i.v. on day 1 followed by 7 days oral treatment with one 15 mg tablet daily, and 91 patients received diclofenac 75 mg i.m. on day 1 followed by 7 days treatment with one 100 mg slow release tablet daily. Pain on movement and limitation of activities were assessed by patients and physicians using questionnaires. Meloxicam i.v. demonstrated a significantly faster median time of onset of analgesic action (30 minutes), compared with diclofenac i.m. (60 minutes). The reduction in pain during movement 30 minutes after injection was also significantly in favour of meloxicam. Assessments of global efficacy indicated that meloxicam was significantly better than diclofenac as rated by investigators (p = 0.02) and patients (p = 0.01). Moreover, the rating of investigators and patients for local and global tolerance was significantly in favour of meloxicam (p < 0.05) and improvements in the quality of life were almost significant (p = 0.053). Fewer adverse events, particularly of a gastrointestinal (GI) nature, occurred in the meloxicam group compared with the diclofenac group. This study therefore demonstrates that meloxicam 15 mg i.v. followed by oral therapy is both efficacious and well tolerated in the treatment of acute lumbago, and compares favourably with the standard NSAID, diclofenac, in this indication.", "Twenty-eight outpatients with chronic severe lumbar pain participated in a double-blind comparative trial on the clinical efficacy of orally administered piroxicam and indomethacin. Half of the patients received indomethacin, 25 mg t.i.d.; the other half received piroxicam 20 mg in the morning and a placebo at lunchtime and before dinner for six weeks. The patients were examined four times at two-week intervals for their capability to do daily tasks and for total lumbar mobility, forward bending, raising of both legs straight and the subjective assessment of pain. Side effects were recorded on a questionnaire and with laboratory tests. The overall results of both groups were similar. Thus, piroxicam, 20 mg daily, matches indomethacin, 25 mg t.i.d., in the treatment of low back pain. The side effects were slight. Treatment with indomethacin was stopped in one case (erythema and conjunctivitis). In the piroxicam group diarrhea, constipation, and pain in the tongue were reported, whereas in the indomethacin group gastrointestinal irritation and tiredness were typical symptoms.", "To compare the efficacy of valdecoxib 40 mg q.d. (with a second dose on day 1) with diclofenac 75 mg b.i.d. in the treatment of acute low back pain.\n This was a multicenter, randomized, double-blind study. Patients with acute low back pain, class 1a or 2a (Quebec Task Force), with a visual analog scale score >/=50 mm (on a 100-mm scale) and moderate to severe pain on a categorical scale, were randomized to valdecoxib 40 mg q.d. (with a second dose on day 1) or diclofenac 75 mg b.i.d. for 7 days (170 patients per group). The primary efficacy end point was change in pain intensity (visual analog scale, mm) from baseline to day 3 for the per-protocol population.\n Least squares mean reductions in pain intensity from baseline to day 3 were similar for valdecoxib (-42.02 mm) and diclofenac (-41.43 mm). Valdecoxib was comparable to diclofenac as the lower limit of the 95% confidence interval of the estimated difference (0.59 mm; 95% confidence interval, -3.40 to 4.59 mm) was within the prespecified noninferiority margin of -10 mm. The overall incidence of adverse events was similar for valdecoxib (28%) and diclofenac (26%). No statistically different moderate or severe upper gastrointestinal adverse events were reported, although they were numerically greater for diclofenac (8) than for valdecoxib (3).\n Valdecoxib 40 mg q.d. (with a second dose on day 1) provides effective relief for acute low back pain, and was at least as efficacious as diclofenac 75 mg b.i.d., with a nonsignificant but numerically lower incidence of gastrointestinal adverse events.", "Seventy out-patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal. Half of the patients received 200 mg meptazinol or 250 mg diflunisal 4-times daily for up to 3 weeks, depending on the duration of pain. Patients were examined 4 times at 1-week intervals for their capability to do daily tasks, for their capacity for forward bending, thoraco-lumbar torsion, straight leg raising, static hip flexion and sit-ups, and for subjective assessment of pain. Side-effects were recorded on a questionnaire. Both treatments produced marked improvement in most of the parameters assessed, often within the first week and, overall, the results were similar with the two drugs. Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal." ]

[ "16076821", "14511967" ]

[ "Effectiveness of the Antenatal Psychosocial Health Assessment (ALPHA) form in detecting psychosocial concerns: a randomized controlled trial.", "IDentify, Educate and Alert (IDEA) trial: an intervention to reduce postnatal depression." ]

[ "A pregnant woman's psychological health is a significant predictor of postpartum outcomes. The Antenatal Psychosocial Health Assessment (ALPHA) form incorporates 15 risk factors associated with poor postpartum outcomes of woman abuse, child abuse, postpartum depression and couple dysfunction. We sought to determine whether health care providers using the ALPHA form detected more antenatal psychosocial concerns among pregnant women than providers practising usual prenatal care.\n A randomized controlled trial was conducted in 4 communities in Ontario. Family physicians, obstetricians and midwives who see at least 10 prenatal patients a year enrolled 5 eligible women each. Providers in the intervention group attended an educational workshop on using the ALPHA form and completed the form with enrolled women. The control group provided usual care. After the women delivered, both groups of providers identified concerns related to the 15 risk factors on the ALPHA form for each patient and rated the level of concern. The primary outcome was the number of psychosocial concerns identified. Results were controlled for clustering.\n There were 21 (44%) providers randomly assigned to the ALPHA group and 27 (56%) to the control group. A total of 227 patients participated: 98 (43%) in the ALPHA group and 129 (57%) in the control group. ALPHA group providers were more likely than control group providers to identify psychosocial concerns (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-3.0; p = 0.02) and to rate the level of concern as \"high\" (OR 4.8, 95% CI 1.1-20.2; p = 0.03). ALPHA group providers were also more likely to detect concerns related to family violence (OR 4.8, 95% CI 1.9-12.3; p = 0.001).\n Using the ALPHA form helped health care providers detect more psychosocial risk factors for poor postpartum outcomes, especially those related to family violence. It is a useful prenatal tool, identifying women who would benefit from additional support and interventions.", "To test the effectiveness of a prenatal intervention in reducing the incidence of postnatal depression.\n A randomized controlled trial.\n A large metropolitan obstetric hospital.\n Pregnant women with risk factors for postnatal depression.\n Women attending their first prenatal visit at the Royal Women's Hospital, Brisbane, were screened for risk factors for postnatal depression (IDentify). Positively screened women were randomly allocated to the intervention group or the control group. The intervention consisted of a booklet about postnatal depression, which included contact numbers; prenatal screening using the Edinburgh Postnatal Depression Scale; a discussion with the woman about her risk of developing postnatal depression (Educate); and a letter to the woman's referring general practitioner and local Child Health Nurse, alerting them of the woman's risk for postnatal depression (Alert).\n Edinburgh Postnatal Depression Scale Score > 12 at 16 weeks postpartum.\n Of the 509 women who were sent a follow-up questionnaire, 371 (72.9%) responded. The proportion of women who reported an Edinburgh Postnatal Depression Scale score of >12 was 26%. There were no significant differences between intervention (46/192, 24%) and control groups (50/177, 28.2%) on this primary outcome measure (OR 0.80; 95% CI 0.50-1.28).\n Over one-quarter of women with risk factors will develop postnatal depression. It is a treatable disorder but under-diagnosis is common. Efforts to reduce postnatal depression by implementing interventions in the prenatal period have been unsuccessful." ]

[ "14982314", "12721239", "16462503", "12619144", "17785709", "17964881", "18797706", "20467301", "17848814", "20651011", "15774341", "19759996", "18581595", "18280104", "19949016", "11157015", "17470863", "15908668", "12748973", "19609570", "19214594", "12471288", "19831159", "20388445", "19242916", "20530648", "19276838", "18779540", "19687337", "15338385", "18591167", "15800330", "15139072", "15274068", "15484202", "18543381", "19064985", "10326708", "12721238", "17307761", "12560436", "19826172", "17785708", "15378098", "18457329", "9243585", "16374892", "7937251", "17530428", "14710804", "19880433" ]

[ "A randomized trial of exercise and quality of life in colorectal cancer survivors.", "Randomized controlled trial of exercise training in postmenopausal breast cancer survivors: cardiopulmonary and quality of life outcomes.", "Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?", "Psychological and fitness changes associated with exercise participation among women with breast cancer.", "Randomized controlled trial of yoga among a multiethnic sample of breast cancer patients: effects on quality of life.", "Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy.", "Effect of exercise on the caloric intake of breast cancer patients undergoing treatment.", "A randomized controlled trial of home-based exercise for cancer-related fatigue in women during and after chemotherapy with or without radiation therapy.", "Randomized controlled trial of a structured training program in breast cancer patients with tumor-related chronic fatigue.", "Cancer-related fatigue and rehabilitation: a randomized controlled multicenter trial comparing physical training combined with cognitive-behavioral therapy with physical training only and with no intervention.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Home-based exercise to alleviate fatigue and improve functional capacity among breast cancer survivors.", "Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer.", "Effects of a walking intervention on fatigue-related experiences of hospitalized acute myelogenous leukemia patients undergoing chemotherapy: a randomized controlled trial.", "Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial.", "Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.", "Randomized trial of exercise therapy in women treated for breast cancer.", "Home-based physical activity intervention for breast cancer patients.", "The group psychotherapy and home-based physical exercise (group-hope) trial in cancer survivors: physical fitness and quality of life outcomes.", "Physical activity for men receiving androgen deprivation therapy for prostate cancer: benefits from a 16-week intervention.", "Yoga of Awareness program for menopausal symptoms in breast cancer survivors: results from a randomized trial.", "Effects of exercise on physiological and psychological variables in cancer survivors.", "A 4-week home-based aerobic and resistance exercise program during radiation therapy: a pilot randomized clinical trial.", "Yoga improves quality of life and benefit finding in women undergoing radiotherapy for breast cancer.", "Restorative yoga for women with breast cancer: findings from a randomized pilot study.", "Effects of a scapula-oriented shoulder exercise programme on upper limb dysfunction in breast cancer survivors: a randomized controlled pilot trial.", "A randomized trial to increase physical activity in breast cancer survivors.", "Effects of aerobic exercise training in anemic cancer patients receiving darbepoetin alfa: a randomized controlled trial.", "Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients.", "Effect of aerobic exercise and relaxation training on fatigue and physical performance of cancer patients after surgery. A randomised controlled trial.", "Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy.", "Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy.", "Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma.", "A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.", "Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.", "Medical Qigong for cancer patients: pilot study of impact on quality of life, side effects of treatment and inflammation.", "Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer.", "Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy.", "Resistance exercise in men receiving androgen deprivation therapy for prostate cancer.", "Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.", "Effect of upper extremity exercise on secondary lymphedema in breast cancer patients: a pilot study.", "Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial.", "Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.", "The effect of seated exercise on fatigue and quality of life in women with advanced breast cancer.", "Effect of exercise on upper extremity pain and dysfunction in head and neck cancer survivors: a randomized controlled trial.", "Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer.", "A pilot study of yoga for breast cancer survivors: physical and psychological benefits.", "A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy.", "Effects of a combined aerobic and resistance exercise program in breast cancer survivors: a randomized controlled trial.", "Feasibility of exercise during treatment for multiple myeloma.", "Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial." ]

[ "We conducted a randomized controlled trial to determine the effects of a home-based exercise intervention on change in quality of life (QOL) in recently resected colorectal cancer survivors, most of whom were receiving adjuvant therapy. Participants were randomly assigned in a 2:1 ratio to either an exercise (n = 69) or control (n = 33) group. The exercise group was asked to perform moderate intensity exercise 3-5 times per week for 20-30 min each time. The primary outcome was change in QOL as measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale. Adherence in the exercise group was good (75.8%) but contamination in the control group was problematic (51.6%). Intention-to-treat analysis revealed no significant differences between groups for change in the FACT-C (mean difference, -1.3; 95% CI, -7.8 to 5.1; P = 0.679). In an 'on-treatment' ancillary analysis, we compared participants who decreased versus increased their cardiovascular fitness over the course of the intervention. This analysis revealed significant differences in favour of the increased fitness group for the FACT-C (mean difference, 6.5; 95% CI, 0.4-12.6; P = 0.038). These data suggest that increased cardiovascular fitness is associated with improvements in QOL in colorectal cancer survivors but better controlled trials are needed.", "To determine the effects of exercise training on cardiopulmonary function and quality of life (QOL) in postmenopausal breast cancer survivors who had completed surgery, radiotherapy, and/or chemotherapy with or without current hormone therapy use.\n Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control (n = 28) group. The exercise group trained on cycle ergometers three times per week for 15 weeks at a power output that elicited the ventilatory equivalent for carbon dioxide. The control group did not train. The primary outcomes were changes in peak oxygen consumption and overall QOL from baseline to postintervention. Peak oxygen consumption was assessed by a graded exercise test using gas exchange analysis. Overall QOL was assessed by the Functional Assessment of Cancer Therapy-Breast scale.\n Fifty-two participants completed the trial. The exercise group completed 98.4% of the exercise sessions. Baseline values for peak oxygen consumption (P =.254) and overall QOL (P =.286) did not differ between groups. Peak oxygen consumption increased by 0.24 L/min in the exercise group, whereas it decreased by 0.05 L/min in the control group (mean difference, 0.29 L/min; 95% confidence interval [CI], 0.18 to 0.40; P <.001). Overall QOL increased by 9.1 points in the exercise group compared with 0.3 points in the control group (mean difference, 8.8 points; 95% CI, 3.6 to 14.0; P =.001). Pearson correlations indicated that change in peak oxygen consumption correlated with change in overall QOL (r = 0.45; P <.01).\n Exercise training had beneficial effects on cardiopulmonary function and QOL in postmenopausal breast cancer survivors.", "Fatigue has a significant impact on the quality of life (QOL) of cancer patients. Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment. In this project, we examined the impact that participation in a randomized controlled trial of a multidisciplinary intervention designed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment.\n Patients with newly diagnosed cancer were randomly assigned to an 8-session structured multidisciplinary intervention or a standard-care arm at the beginning of their course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were led by either a psychiatrist or psychologist, collaborating with a nurse, physical therapist, chaplain, or social worker, depending on the session's theme. The fatigue assessments used in this trial included the Linear Analogue Self Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS).\n There were 115 participants enrolled and the 2 randomization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm (P = 0.042). Most of scores indicated less fatigue (higher score) in the standard treatment group, but there were no statistically significant differences found at baseline and weeks 4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting significant fatigue in the standard treatment arm. For the entire participant population, fatigue levels initially worsened with radiotherapy, stabilized at week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and radiotherapy dose did not have a significant impact on fatigue levels.\n Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline. Clinically, this structured multidisciplinary intervention had no impact on fatigue, and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment.", "Exercise participation has been shown to improve cardiovascular fitness and reduce psychological distress among women receiving chemotherapy and/or radiation. The purpose of this pilot study was to examine the changes in distress and body image, and fitness following exercise participation among 24 women who had been diagnosed with breast cancer within the previous 3 years. The women were randomly assigned to participate in a 12-week supervised aerobic exercise program in a hospital setting or a wait-list control group. Assessments of distress and body image were conducted at pre- and post-treatment. Data showed that the women in the exercise group improved significantly in body image (Physical Condition and Weight Concerns subscales) vs control group participants at post-treatment. Reductions in distress were also noted in the exercise group, but these were nonsignificant. At post-treatment, there were modest improvements in fitness in the exercise group.\n Copyright 2002 John Wiley & Sons, Ltd.", "This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients.\n One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment.\n Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02).\n Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.", "To show fatigue prevention and quality of life (QOL) improvement from cardiovascular exercise during radiotherapy.\n Prospective enrollment (n=21), randomized to exercise (n=11) and control groups (n=10), with pre- and post-radiotherapy between- and within-group comparisons.\n Academic medical center.\n Localized prostate cancer patients undergoing radiotherapy.\n The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise.\n Pre- and post-radiotherapy differences in cardiac fitness, fatigue, depression, functional status, physical, social, and functional well-being, leg strength, and flexibility were examined within and between 2 groups.\n No significant differences existed between 2 groups at pre-radiotherapy assessment. At post-radiotherapy assessment, the exercise group showed significant within group improvements in: cardiac fitness (P<.001), fatigue (P=.02), Functional Assessment of Cancer Therapy-Prostate (FACT-P) (P=.04), physical well-being (P=.002), social well-being (P=.02), flexibility (P=.006), and leg strength (P=.000). Within the control group, there was a significant increase in fatigue score (P=.004) and a decline in social well-being (P<.05) at post-radiotherapy assessment. Between-group differences at post-radiotherapy assessment were significant in cardiac fitness (P=.006), strength (P=.000), flexibility (P<.01), fatigue (P<.001), FACT-P (P=.006), physical well-being (P<.001), social well-being (P=.002), and functional well-being (P=.04).\n An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness, flexibility, muscle strength, and overall QOL and prevented fatigue.", "The purpose of this study was to examine the effects of an exercise intervention on the total caloric intake (TCI) of breast cancer patients undergoing treatment. A secondary purpose was to determine whether or not a relationship existed between changes in TCI, body fat composition (%BF), and fatigue during the study, which lasted 6 months. Twenty females recently diagnosed with breast cancer, scheduled to undergo chemotherapy or radiation, were assigned randomly to an experimental (N = 10) or control group (N = 10). Outcome measures included TCI (3-day food diary), %BF (skinfolds), and fatigue (revised Piper Fatigue Scale). Each exercise session was conducted as follows: initial cardiovascular activity (6-12 min), followed by stretching (5-10 min), resistance training (15-30 min), and a cool-down (approximately 8 min). Significant changes in TCI were observed among groups (F1,18 = 8.582; P = 0.009), at treatments 2 and 3, and at the end of the study [experimental (1973 +/- 419), control (1488 +/- 418); experimental (1946 +/- 437), control (1436 +/- 429); experimental (2315 +/- 455), control (1474 +/- 294), respectively]. A significant negative correlation was found (Spearman rho(18) = -0.759; P < 0.001) between TCI and %BF and between TCI and fatigue levels (Spearman rho(18) = -0.541; P = 0.014) at the end of the study. In conclusion, the results of this study suggest that an exercise intervention administered to breast cancer patients undergoing medical treatment may assist in the mitigation of some treatment side effects, including decreased TCI, increased fatigue, and negative changes in body composition.", "Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment.\n The purpose of this study was to evaluate the effectiveness of a home-based exercise training intervention, the Pro-self Fatigue Control Program on the management of cancer-related fatigue.\n Participants (N = 119) were randomized into 1 of 3 groups: group 1 received the exercise prescription throughout the study; group 2 received their exercise prescription after completing cancer treatment; and group 3 received usual care. Patients completed the Piper Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies-Depression Scale, and Worst Pain Intensity Scale.\n All groups reported mild fatigue levels, sleep disturbance, and mild pain, but not depression. Using multilevel regression analysis, significant linear and quadratic trends were found for change in fatigue and pain (ie, scores increased, then decreased over time). No group differences were found in the changing scores over time. A significant quadratic effect for the trajectory of sleep disturbance was found, but no group differences were detected over time. No significant time or group effects were found for depression.\n Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment. The optimal timing of exercise remains to be determined.\n Clinicians need to be aware that some physical activity is better than none, and there is no harm in exercise as tolerated during cancer treatment. Further analysis is needed to examine the adherence to exercise. More frequent assessments of fatigue, sleep disturbance, depression, and pain may capture the effect of exercise.", "Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment. The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies. In a randomized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated.\n 63 breast cancer patients with cancer-related chronic fatigue were randomized at the beginning of the inpatient rehabilitation. The control group received the standard complex rehabilitation program, the intervention group a structured physical training program and additional muscle strength and aerobic exercises. The effects of the treatment were evaluated by questionnaires at the start of rehabilitation (t1), end of rehabilitation (t2), and 3 months after t2 (t3). Isometric muscle strength and aerobic capacity were evaluated at t1 and t2.\n There was an improvement of muscle strength at the end of rehabilitation for both groups. The increase from t1 to t2 was significantly higher for the training group. The scores for global quality of life, physical well-being, and functionality increased from t1 to t2, but further improvement in the follow-up (t3) was only observed in the training group. The cancer-related fatigue was significantly reduced in the training group from t1 to t3, however, not in the control group.\n Structured physical training programs initiated during inpatient rehabilitation and continuously practiced in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients.", "Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial.\n This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with cognitive behavioral therapy with physical training alone and with no intervention.\n In this multicenter randomized controlled trial, 147 survivors of cancer were randomly assigned to a group that received physical training combined with cognitive-behavioral therapy (PT+CBT group, n=76) or to a group that received physical training alone (PT group, n=71). In addition, a nonintervention control group (WLC group) consisting of 62 survivors of cancer who were on the waiting lists of rehabilitation centers elsewhere was included.\n The study was conducted at 4 rehabilitation centers in the Netherlands.\n All patients were survivors of cancer.\n Physical training consisting of 2 hours of individual training and group sports took place twice weekly, and cognitive-behavioral therapy took place once weekly for 2 hours.\n Fatigue was assessed with the Multidimensional Fatigue Inventory before and immediately after intervention (12 weeks after enrollment). The WLC group completed questionnaires at the same time points.\n Baseline fatigue did not differ significantly among the 3 groups. Over time, levels of fatigue significantly decreased in all domains in all groups, except in mental fatigue in the WLC group. Analyses of variance of postintervention fatigue showed statistically significant group effects on general fatigue, on physical and mental fatigue, and on reduced activation but not on reduced motivation. Compared with the WLC group, the PT group reported significantly greater decline in 4 domains of fatigue, whereas the PT+CBT group reported significantly greater decline in physical fatigue only. No significant differences in decline in fatigue were found between the PT+CBT and PT groups.\n Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.", "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.", "This pilot study examined the efficacy of two home-based exercise programs on alleviating fatigue and improving functional capacity in breast cancer survivors. Participants were randomly assigned into one of three groups: aerobic exercise (AE), resistance exercise (RE), or usual care control (CON). After receiving individualized instruction and training, participants assigned to the AE and RE groups were asked to perform the prescribed exercise(s) 3 times per week for 12 weeks at home. Both groups were instructed to keep their perceived exercise intensity in the \"fairly light\" to \"somewhat hard\" range using the Borg Perceived Exertion Scale. All participants completed the revised Piper Fatigue Scale (PFS) and the 6-minute walk test (6MWT) at baseline and 12-week post-exercise program. Analysis of pre- and post-training data revealed a significant reduction in fatigue levels on the PFS among participants in the AE group (Z=2.521, one-tailed P=0.006), and a significant improvement in the distance of the 6MWT for the RE group (Z=2.366, one-tailed P=0.009) at the end of 12-week study period. No significant changes in fatigue or functional status were observed in the CON group. Findings provide preliminary support for RE as a viable strategy for improving functional capacity in breast cancer survivors, while AE may be more effective in attenuating cancer-related fatigue. Incorporating RE training for future research may help advance the growing body of knowledge in symptom management for breast cancer survivors.", "Postoperative radiotherapy for breast cancer has a number of associated complications. This study examined whether supervised moderate-intensity exercise could mitigate the complications that occur during radiotherapy.\n Forty women were randomized before radiotherapy after various operations for breast cancer. Seventeen patients who were assigned to the exercise group performed supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks. Twenty-three patients in the control group were asked to perform self-shoulder stretching exercise. The World Health Organization Quality of Life-BREF (WHOQOL-BREF), brief fatigue inventory (BFI), range of motion (ROM) of the shoulder, and pain score were assessed before and after radiotherapy.\n There were no significant differences noted at baseline between groups. In the exercise group, there was an increase in the WHOQOL-BREF and shoulder ROM and decrease in BFI and pain score after radiotherapy. On the other hand, patients in the control group showed decrease in the WHOQOL-BREF and shoulder ROM and increase in BFI and pain score after radiotherapy. There were statistically significant differences in the changes in the WHOQOL, BFI, shoulder ROM, and pain score between the groups.\n Patients receiving radiotherapy for breast cancer may benefit in physical and psychological aspects from supervised moderate-intensity exercise therapy.", "The purpose of this randomized, controlled clinical trial was to preliminarily examine the effects of a three-week walking exercise program (WEP) on fatigue-related experiences of acute myelogenous leukemia (AML) patients receiving chemotherapy. Eligible AML patients were randomly assigned to either an experimental group (n=11), which received 12 minutes of WEP per day, five days per week for three consecutive weeks, or to a control group (n=11), which received standard ward care. Effects of the WEP were assessed by seven indicators: worst and average fatigue intensities, fatigue interference with patients' daily life, 12-minute walking distance, overall symptom distress, anxiety, and depressive status. All patients were evaluated four times: before chemotherapy (baseline or Day 1), Day 7, Day 14, and Day 21 of chemotherapy. Data were analyzed by Generalized Estimating Equation and revealed that AML patients in the three-week WEP group had a significantly greater increase in 12-minute walking distance than the control group. Patients in the WEP also had lower levels of fatigue intensity and interference, symptom distress, anxiety, and depressive status than the control group. Although preliminary, our results strongly suggest that three weeks of systematic walking exercise is clinically feasible for AML patients undergoing chemotherapy and can effectively improve their fatigue-related experiences.", "Androgen suppression therapy (AST) results in musculoskeletal toxicity that reduces physical function and quality of life. This study examined the impact of a combined resistance and aerobic exercise program as a countermeasure to these AST-related toxicities.\n Between 2007 and 2008, 57 patients with prostate cancer undergoing AST (commenced > 2 months prior) were randomly assigned to a program of resistance and aerobic exercise (n = 29) or usual care (n = 28) for 12 weeks. Primary end points were whole body and regional lean mass. Secondary end points were muscle strength and function, cardiorespiratory capacity, blood biomarkers, and quality of life.\n Analysis of covariance was used to compare outcomes for groups at 12 weeks adjusted for baseline values and potential confounders. Patients undergoing exercise showed an increase in lean mass compared with usual care (total body, P = .047; upper limb, P < .001; lower limb, P = .019) and similarly better muscle strength (P < .01), 6-meter walk time (P = .024), and 6-meter backward walk time (P = .039). Exercise also improved several aspects of quality of life including general health (P = .022) and reduced fatigue (P = .021) and decreased levels of C-reactive protein (P = .008). There were no adverse events during the testing or exercise intervention program.\n A relatively brief exposure to exercise significantly improved muscle mass, strength, physical function, and balance in hypogonadal men compared with normal care. The exercise regimen was well tolerated and could be recommended for patients undergoing AST as an effective countermeasure to these common treatment-related adverse effects.", "Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer.\n One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks.\n Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy.\n Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.", "To examine the effects of aerobic exercise therapy on quality of life (QoL) and associated outcomes in women treated for breast cancer. Evidence suggests that exercise may be beneficial, but no trial has included an exercise-placebo and a usual-care group to control for the attention effects that might be associated with aerobic exercise interventions in cancer patients.\n A total of 108 women who had been treated for breast cancer 12 to 36 months previously were randomly assigned to supervised aerobic exercise therapy (n = 34), exercise-placebo (body conditioning; n = 36), or usual care (n = 38). Exercise therapy and exercise-placebo sessions took place three times per week for 8 weeks. Outcomes included QoL, depression, exercise behavior, aerobic fitness; outcomes were assessed at baseline and at the 8- and 24-week follow-up.\n Analyses of covariance revealed a significant mean difference of 9.8 units in Functional Assessment of Cancer Therapy-General (primary outcome) favoring aerobic exercise therapy at 8 weeks, relative to usual care. Significant differences that favored aerobic exercise therapy relative to usual care were recorded for Functional Assessment of Cancer Therapy-Breast, social/family well-being, functional well-being, and breast cancer subscale scores at 8-week follow-up. Psychological health outcomes improved modestly for both intervention groups; these improvements were sustained for several end points.\n Exercise therapy had large, clinically meaningful, short-term beneficial effects on QoL in women treated for breast cancer; this finding cannot be attributable to attention, given that the exercise-placebo group did not report similar effects relative to usual care.", "The efficacy of a home-based physical activity (PA) intervention for early-stage breast cancer patients was evaluated in a randomized controlled trial.\n Eighty-six sedentary women (mean age, 53.14 years; standard deviation, 9.70 years) who had completed treatment for stage 0 to II breast cancer were randomly assigned to a PA or contact control group. Participants in the PA group received 12 weeks of PA counseling (based on the Transtheoretical Model) delivered via telephone, as well as weekly exercise tip sheets. Assessments were conducted at baseline, after treatment (12 weeks), and 6 and 9 month after baseline follow-ups. The post-treatment outcomes are reported here.\n Analyses showed that, after treatment, the PA group reported significantly more total minutes of PA, more minutes of moderate-intensity PA, and higher energy expenditure per week than controls. The PA group also out-performed controls on a field test of fitness. Changes in PA were not reflected in objective activity monitoring. The PA group was more likely than controls to progress in motivational readiness for PA and to meet PA guidelines. No significant group differences were found in body mass index and percent body fat. Post-treatment group comparisons revealed significant improvements in vigor and a reduction in fatigue in the PA group. There was a positive trend in intervention effects on overall mood and body esteem.\n The intervention successfully increased PA and improved fitness and specific aspects of psychological well-being among early-stage breast cancer patients. The success of a home-based PA intervention has important implications for promoting recovery in this population.", "Physical exercise has been shown to enhance quality of life (QOL) in cancer survivors using pretest-posttest designs and compared to usual care (i.e. no intervention). In the present study, we conducted a randomized controlled trial to determine if exercise could improve QOL in cancer survivors beyond the known benefits of group psychotherapy (GP). We matched 22 GP classes (N=108) on content and then randomly assigned 11 (n=48) to GP alone and 11 (n=60) to GP plus home-based, moderate-intensity exercise (GP+EX). Participants completed a physical fitness test and QOL measures (e.g. Functional Assessment of Cancer Therapy scales) at the beginning and end of GP classes (about 10 weeks). We had excellent recruitment (81%), retention (89%), and adherence (84%) rates and a modest contamination (22%) rate. Using intention-to-treat repeated measures analyses of variance, we found significant Time by Condition interactions for functional well-being, fatigue, and sum of skinfolds. We also found borderline significant interactions for physical well-being, satisfaction with life, and flexibility. All interactions favored the GP+EX condition. We conclude that a home-based, moderate intensity exercise program may im-prove QOL in cancer survivors beyond the benefits of GP, particularly in relation to physical and functional well-being.\n Copyright 2003 John Wiley & Sons, Ltd.", "Prostate cancer patients receiving androgen deprivation therapy (ADT) are vulnerable to a number of potentially debilitating side effects, which can significantly impact quality of life. The role of alternate therapies, such as physical activity (PA), in attenuating these side effects is largely understudied for such a large population. Thus, the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior, quality of life, and fitness measures.\n One hundred participants were randomized into an intervention (n = 53) or a wait-list control group (n = 47), with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing. The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions. PA, quality of life, fitness, and physiological outcomes were assessed pre and post the 16-week intervention.\n Significant increases in PA, supported by changes in girth measures and blood pressure, support the beneficial impact of the intervention. Positive trends were also evident for depression and fatigue. However, due to the high dropout rate, these results must be interpreted with caution.\n PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy. Determining the maintenance of this behavior change will be important for understanding how the long-term benefits of increased activity levels may alleviate the late effects of ADT.", "Breast cancer survivors have limited options for the treatment of hot flashes and related symptoms. Further, therapies widely used to prevent recurrence in survivors, such as tamoxifen, tend to induce or exacerbate menopausal symptoms. The aim of this preliminary, randomized controlled trial was to evaluate the effects of a yoga intervention on menopausal symptoms in a sample of survivors of early-stage breast cancer (stages IA-IIB).\n Thirty-seven disease-free women experiencing hot flashes were randomized to the 8-week Yoga of Awareness program (gentle yoga poses, meditation, and breathing exercises) or to wait-list control. The primary outcome was daily reports of hot flashes collected at baseline, posttreatment, and 3 months after treatment via an interactive telephone system. Data were analyzed by intention to treat.\n At posttreatment, women who received the yoga program showed significantly greater improvements relative to the control condition in hot-flash frequency, severity, and total scores and in levels of joint pain, fatigue, sleep disturbance, symptom-related bother, and vigor. At 3 months follow-up, patients maintained their treatment gains in hot flashes, joint pain, fatigue, symptom-related bother, and vigor and showed additional significant gains in negative mood, relaxation, and acceptance.\n This pilot study provides promising support for the beneficial effects of a comprehensive yoga program for hot flashes and other menopausal symptoms in early-stage breast cancer survivors.", "The primary purpose of this study was to examine the effect of aerobic exercise on physiological and psychological function in patients rehabilitating from cancer treatment. A second purpose was to evaluate the differential effects of low- and moderate-intensity exercise on these variables.\n Eighteen survivors of breast or colon cancer (15 female and 3 male, 40-65 yr of age) served as subjects. The subjects were matched by aerobic capacity and scores on a Quality of Life questionnaire, and then randomly assigned to a control, low- (25-35% heart rate reserve (HRR)), or a moderate- (40-50% HRR) intensity exercise group. The exercise groups performed lower-body aerobic exercise three times a week for 10 wk. After the exercise training, there were no statistically significant differences between the two exercise groups on any of the physiological variables. Therefore, the exercise groups were combined into one group for the final analysis.\n The results revealed statistically significant increases in aerobic capacity (P < 0.001) and lower-body flexibility (P = 0.027), a significant decrease in body fat (P < 0.001), and a significant increase in quality of life (P < 0.001) and a measure of energy (P = 0.038) in the exercise group when compared with the control group.\n Low- and moderate-intensity aerobic-exercise programs were equally effective in improving physiological and psychological function in this population of cancer survivors. Aerobic exercise appears to be a valuable and well-tolerated component of the cancer-rehabilitation process.", "During radiation therapy, cancer patients may report cancer-related fatigue (CRF), which impairs aerobic capacity, strength, muscle mass, and, ultimately, quality of life (QOL). The purpose of this pilot clinical trial was to examine the feasibility and initial efficacy of a home-based aerobic and progressive resistance exercise intervention for aerobic capacity, strength, muscle mass, CRF, and QOL. Daily steps walked (DSW), daily minutes of resistance exercise (MRE), and number of resistance exercise days (RED) were assessed to evaluate intervention adherence. Breast and prostate cancer patients (n = 38) beginning radiation therapy were randomized to undergo 4 weeks of exercise or no exercise. Participants in the exercise group demonstrated good adherence to the exercise intervention, with significantly more DSW, MRE, and RED at post intervention and 3 month follow-up than controls. Participants in the exercise intervention exhibited significantly higher QOL and significantly lower CRF post intervention and at 3-month follow-up than controls. Results of this pilot study provide positive preliminary evidence that exercise during radiation may be beneficial for cancer patients.", "This study examined the effects of yoga on quality of life (QOL) and psychosocial outcomes in women with breast cancer undergoing radiotherapy. Sixty-one women were randomly assigned to either a yoga or a wait-list group. Yoga classes were taught biweekly during the 6 weeks of radiotherapy. Participants completed measures of QOL, fatigue, benefit finding (finding meaning in the cancer experience), intrusive thoughts, sleep disturbances, depressive symptoms, and anxiety before radiotherapy and then again 1 week, 1 month, and 3 months after the end of radiotherapy. General linear model analyses revealed that compared to the control group, the yoga group reported significantly better general health perception (p = .005) and physical functioning scores (p = .04) 1 week postradiotherapy; higher levels of intrusive thoughts 1 month postradiotherapy (p = .01); and greater benefit finding 3 months postradiotherapy (p = .01). There were no other group differences in other QOL subscales for fatigue, depression, or sleep scores. Exploratory analyses indicated that intrusive thoughts 1 month after radiotherapy were significantly positively correlated with benefit finding 3 months after radiotherapy (r = .36, p = .011). Our results indicated that the yoga program was associated with statistically and clinically significant improvements in aspects of QOL.", "Restorative yoga (RY) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors. Study goals were: to determine the feasibility of implementing a RY intervention for women with breast cancer; and to examine group differences in self-reported emotional, health-related quality of life, and symptom outcomes.\n Women with breast cancer (n=44; mean age 55.8 years) enrolled in this study; 34% were actively undergoing cancer treatment. Study participants were randomized to the intervention (10 weekly 75-minute RY classes) or a waitlist control group. Participants completed questionnaires at Week 0 (baseline) and Week 10 (immediately post-intervention for the yoga group).\n Group differences favoring the yoga group were seen for mental health, depression, positive affect, and spirituality (peace/meaning). Significant baseline*group interactions were observed for negative affect and emotional well-being. Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group. The yoga group demonstrated a significant within-group improvement in fatigue; no significant difference was noted for the control group.\n Although limited by sample size, these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients. This study demonstrates that a RY intervention is feasible for women with breast cancer; implications for study design and implementation are noted with an emphasis on program adoption and participant adherence.\n (c) 2009 John Wiley & Sons, Ltd.", "To examine the effects of a scapula-oriented exercise on upper limb dysfunction in breast cancer survivors.\n A prospective randomized, controlled pilot trial with historical control.\n Rehabilitation department at a university hospital.\n Thirty-two women with breast cancer were randomly assigned to scapula-oriented exercise group (n = 16) and general exercise group (n = 16). An historical control group (n = 18) without exercise was enrolled from breast cancer survivors.\n The scapula-oriented exercises were designed focusing on scapulothoracic movement. The general exercise group performed body conditioning exercise. Exercise therapies were performed for one session per week for eight weeks.\n Pain and physical disabilities related to upper limb dysfunction, quality of life and depression were used as subjective outcomes. Objective outcome measures included shoulder range of motion and strength. Outcomes were assessed at baseline and post exercise.\n At baseline, no significant difference was observed among the three groups. The scapula-oriented exercise group showed improvements in pain, physical function, social function, and global quality of life compared with baseline, whereas the general exercise group showed improved fatigue and range of motion. The change in global quality of life (P = 0.067; effect size, 0.33) and strength of external rotation (P = 0.001; effect size, 0.55) were significantly greater in the scapula-oriented exercise group than in the general exercise and control group.\n Scapula-oriented exercise had beneficial effects on pain, quality of life and aspects of strength. The sample size required in a larger definitive study is 32 subjects per group.", "Interventions to increase physical activity among breast cancer survivors are needed to improve health and quality of life and possibly to reduce the risk of disease recurrence and early mortality. Therefore, we report the feasibility and preliminary outcomes of a pilot randomized trial designed to increase physical activity in sedentary breast cancer survivors receiving hormone therapy.\n Forty-one sedentary women on estrogen receptor modulators or aromatase inhibitors for stage I, II, or IIIA breast cancer were randomly assigned to receive a 12-wk multidisciplinary physical activity behavior change intervention or usual care.\n Recruitment was 34%, intervention adherence was 99%, and complete follow-up data were obtained on 93%. Most participants (93%) were white with mean age of 53 +/- 9 yr. Differences favoring the intervention group were noted for accelerometer physical activity counts (mean difference = 72,103; 95% confidence interval (CI) = 25,383-119,000; effect size (d) = 1.02; P = 0.004), aerobic fitness (mean difference = 2.9; 95% CI = -0.1 to 5.8; d = 0.64; P = 0.058), back/leg muscle strength (mean difference = 12.3; 95% CI = 0.4-15.9; d = 0.81; P = 0.017), waist-to-hip ratio (mean difference = -0.05; 95% CI = -0.01 to -0.08; d = -0.77; P = 0.018), and social well-being (mean difference = 2.0; 95% CI = 0.3-3.8; d = 0.76; P = 0.03). However, the intervention group also reported a greater increase in joint stiffness (mean difference = 1.1; 95% CI = 0.1-2.2; d = 0.70; P = 0.04).\n A behavior change intervention for breast cancer survivors based on the social cognitive theory is feasible and results in potentially meaningful improvements in physical activity and selected health outcomes. Confirmation in a larger study is warranted.", "Anemia in patients with solid tumors is a common problem that is associated with impaired exercise capacity, increased fatigue, and lower quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) have been shown to improve these outcomes; however, it is unknown if additional benefits can be achieved with aerobic exercise training.\n We conducted a single-center, prospective, randomized, controlled trial in 55 mild-to-moderately anemic patients with solid tumors. Patients were randomized to either darbepoetin alfa alone (DAL, n = 29) or darbepoetin alfa plus aerobic exercise training (DEX; n = 26). The DEX group performed aerobic exercise training three times per week at 60%-100% of baseline exercise capacity for 12 weeks. The primary endpoint was QoL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary endpoints were fatigue, cardiorespiratory fitness (VO(2peak)), hemoglobin (Hb) response, and darbepoetin alfa dosing.\n Intention-to-treat analyses indicated significant improvements in QoL and fatigue in both groups over time but there were no between-group differences. The DEX group had a significantly greater VO(2peak) than the DAL group (mean group difference, +3.0 ml/kg per minute; 95% confidence interval, 1.2-4.7; p = .001) and there were borderline significant differences in favor of the DEX group for Hb response and darbepoetin alfa dosing.\n Aerobic exercise training did not improve QoL or fatigue beyond the established benefits of DAL but it did result in favorable improvements in exercise capacity and a more rapid Hb response with lower dosing requirements. Our results may be useful to clinicians despite the more recent restrictions on the indications for ESAs.", "Lymphoma patients commonly experience declines in physical functioning and quality of life (QoL) that may be reversed with exercise training.\n We conducted a randomized controlled trial in Edmonton, Alberta, Canada, between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and randomly assigned them to usual care (UC; n = 62) or 12 weeks of supervised aerobic exercise training (AET; n = 60). Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia. Secondary end points were overall QoL, psychosocial functioning, cardiovascular fitness, and body composition.\n Follow-up assessment for our primary end point was 96% (117 of 122) at postintervention and 90% (110 of 122) at 6-month follow-up. Median adherence to the supervised exercise program was 92%. At postintervention, AET was superior to UC for patient-rated physical functioning (mean group difference, +9.0; 95% CI, 2.0 to 16.0; P = .012), overall QoL (P = .021), fatigue (P = .013), happiness (P = .004), depression (P = .005), general health (P < .001), cardiovascular fitness (P < .001), and lean body mass (P = .008). Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning. AET did not interfere with chemotherapy completion rate or treatment response. At 6-month follow-up, AET was still borderline or significantly superior to UC for overall QoL (P = .054), happiness (P = .034), and depression (P = .009) without an increased risk of disease recurrence/progression.\n AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response. Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients.", "Fatigue is a frequent problem after surgical treatment of solid tumours. Aerobic exercise and psychosocial interventions have been shown to reduce the severity of this symptom in cancer patients. Therefore, we compared the effect of the two therapies on fatigue in a randomised controlled study. Seventy-two patients who underwent surgery for lung (n=27) or gastrointestinal tumours (n=42) were assigned to an aerobic exercise group (stationary biking 30 min five times weekly) or a progressive relaxation training group (45 min three times per week). Both interventions were carried out for 3 weeks. At the beginning and the end of the study, we evaluated physical, cognitive and emotional status and somatic complaints with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC-QLQ-30) questionnaire, and maximal physical performance with an ergometric stress test. Physical performance of the training group improved significantly during the programme (9.4+/-20 watts, p=0.01) but remained unchanged in the relaxation group (1.5+/-14.8 watts, p=0.37). Fatigue and global health scores improved in both groups during the intervention (fatigue: training group 21%, relaxation group 19%; global health of both groups 19%, p for all < or =0.01); however, there was no significant difference between changes in the scores of both groups (p=0.67). We conclude that a structured aerobic training programme improves the physical performance of patients recovering from surgery for solid tumours. However, exercise is not better than progressive relaxation training for the treatment of fatigue in this setting.", "To compare the effectiveness of a prescribed home-based walking exercise intervention with usual care in older women receiving hormonal treatment for breast cancer, and to examine relationships among levels of the cortisol, serotonin, interleukin-6, and bilirubin biomarkers and fatigue, sleep disturbances, and depressive symptoms.\n Longitudinal randomized clinical trial.\n A National Cancer Institute-designated cancer center in the southeastern United States.\n 20 women (aged 55 years or older) with breast cancer receiving hormonal treatment.\n Participants were randomized to a walking exercise intervention or usual care. Laboratory samples and the Pittsburgh Sleep Quality Index (PSQI), the Piper Revised Fatigue Scale, and the Center for Epidemiological Studies-Depression Scale were collected at the initial clinic visit and at 12 weeks from the groups. Questionnaires also were collected at weeks 2 and 14.\n Fatigue, sleep disturbances, depressive symptoms, biomarkers, and exercise.\n Effect of the exercise intervention on sleep scores was highly significant between groups. Exercise group scores on the PSQI decreased significantly over time (indicating improved sleep quality), although scores did not change significantly within the control group. Sleep actigraphy also showed significantly shorter actual wake time and less movement in the exercise group. Serotonin levels also were significantly affected by the intervention.\n Data suggest that a walking exercise intervention improves sleep in older women receiving hormonal treatment for their breast cancer. Serotonin levels may be a useful biomarker when assessing sleep disturbances in this group.\n Clinicians need to be aware that older women receiving hormonal treatment for their breast cancer may experience fatigue, sleep disturbances, and depressive symptoms. Homebased walking activity may reduce symptom severity in this group.", "To evaluate the effectiveness of a supervised home-based flexible training program on cardiorespiratory fitness (CRF), mental distress, and health-related quality of life (HRQOL) parameters in young and middle-aged cancer patients shortly after curative chemotherapy.\n One hundred eleven patients age 18 to 50 years who had received chemotherapy for lymphomas or breast, gynecologic, or testicular cancer completed the trial. These patients were randomly allocated to either an intervention group (n = 59), which underwent a 14-week training program, or a control group (n = 52) that received standard care. Primary outcome was change in CRF, as determined by Astrand-Rhyming indirect bicycle ergometer test (maximum oxygen uptake [VO(2max)]), between baseline (T0) and follow-up (T1). Secondary outcomes were mental distress, as assessed by the Hospital Anxiety and Depression Scale, and HRQOL, as assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire. Two-way analysis of covariance was used to analyze changes from T0 to T1.\n VO(2max) increased by 6.4 mL/kg(-1)/min(-1) in patients in the intervention group and by 3.1 mL/kg(-1)/min(-1) in patients in the control group (P < .01). The fatigue score decreased by 17.0 points in the control group compared with only 5.8 points in the intervention group (P < .01). There were no intergroup differences in mental distress or HRQOL.\n A supervised, home-based, flexible training program has significant effect on CRF in young and middle-aged cancer patients shortly after curative chemotherapy, but it has no favorable effect on patients' experience of fatigue, mental distress, or HRQOL.", "Research suggests that stress-reduction programs tailored to the cancer setting help patients cope with the effects of treatment and improve their quality of life. Yoga, an ancient Eastern science, incorporates stress-reduction techniques that include regulated breathing, visual imagery, and meditation as well as various postures. The authors examined the effects of the Tibetan yoga (TY) practices of Tsa lung and Trul khor, which incorporate controlled breathing and visualization, mindfulness techniques, and low-impact postures in patients with lymphoma.\n Thirty-nine patients with lymphoma who were undergoing treatment or who had concluded treatment within the past 12 months were assigned to a TY group or to a wait-list control group. Patients in the TY group participated in 7 weekly yoga sessions, and patients in the wait-list control group were free to participate in the TY program after the 3-month follow-up assessment.\n Eighty nine percent of TY participants completed at least 2-3 three yoga sessions, and 58% completed at least 5 sessions. Patients in the TY group reported significantly lower sleep disturbance scores during follow-up compared with patients in the wait-list control group (5.8 vs. 8.1; P < 0.004). This included better subjective sleep quality (P < 0.02), faster sleep latency (P < 0.01), longer sleep duration (P < 0.03), and less use of sleep medications (P < 0.02). There were no significant differences between groups in terms of intrusion or avoidance, state anxiety, depression, or fatigue.\n The participation rates suggested that a TY program is feasible for patients with cancer and that such a program significantly improves sleep-related outcomes. However, there were no significant differences between groups for the other outcomes.\n Copyright 2004 American Cancer Society.", "Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma.\n Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy.\n There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003).\n Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.", "Fatigue is the most prevalent and debilitating symptom experienced by breast cancer patients receiving adjuvant chemotherapy or radiation therapy and few evidence-based treatments are available to manage this distressing side-effect. The purpose of this multi-institutional randomized controlled trial was to determine the effects of exercise on fatigue levels during treatment for breast cancer. Sedentary women (N=119) with Stage 0-III breast cancer receiving outpatient adjuvant chemotherapy or radiation therapy were randomized to a home-based moderate-intensity walking exercise program or to usual care for the duration of their cancer treatment. Of participants randomized to exercise, 72% adhered to the exercise prescription; 61% of the usual care group adhered. The intention-to-treat analysis revealed no group differences in part because of a dilution of treatment effect as 39% of the usual care group exercised and 28% of the exercise group did not. When exercise participation was considered using the data analysis method of instrumental variables with principal stratification, a clinically important and statistically significant (p=0.03) effect of exercise on pretest-to-posttest change in fatigue levels was demonstrated. Adherence to a home-based moderate-intensity walking exercise program may effectively mitigate the high levels of fatigue prevalent during cancer treatment.", "Quality of life (QOL) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself. Medical Qigong (coordination of gentle exercise and relaxation through meditation and breathing exercise based on Chinese medicine theory of energy channels) may be an effective therapy for improving QOL, symptoms and side effects, and longevity of cancer patients. In this pilot study, the feasibility, acceptability, and impact of Medical Qigong (MQ) were evaluated on outcomes in cancer patients. Thirty patients diagnosed with heterogeneous cancers, were randomly assigned to two groups: a control group that received usual medical care and an intervention group who participated in a MQ program for 8 weeks in addition to receiving usual medical care. Randomization was stratified by completion of cancer treatment (n = 14) or under chemotherapy (n = 16). Patients completed measures before and after the program. Quality of life and symptoms were measured by the EORTC QLQ-C 30 and progress of disease by the inflammation biomarker (CRP: c-reactive protein) via a blood test was assessed. The MQ intervention group reported clinically significant improved global QOL scores pre- and post-intervention. The MQ intervention also reduced the symptoms of side effects of cancer treatment and inflammation biomarker (CRP) compare to the control group. Due to the small sample size, however, the results were not statistically significant between treatment and the control groups. Data from the pilot study suggest that MQ with usual medical treatment can enhance the QOL of cancer patients and reduce inflammation. This study needs a further investigation with a larger sample size.", "Radiotherapy for prostate cancer (PCa) may cause unfavorable changes in fatigue, quality of life (QOL), and physical fitness. We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue, QOL, physical fitness, body composition, prostate-specific antigen, testosterone, hemoglobin, and lipid levels in men with PCa receiving radiotherapy.\n Between 2003 and 2006, we conducted a randomized controlled trial in Ottawa, Canada, where 121 PCa patients initiating radiotherapy with or without androgen deprivation therapy were randomly assigned to usual care (n = 41), resistance (n = 40), or aerobic exercise (n = 40) for 24 weeks. Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale.\n The follow-up assessment rate for our primary end point of fatigue was 92.6%. Median adherence to prescribed exercise was 85.5%. Mixed-model repeated measures analyses indicated both resistance (P =.010) and aerobic exercise (P = .004) mitigated fatigue over the short term. Resistance exercise also produced longer-term improvements (P = .002). Compared with usual care, resistance training improved QOL (P = .015), aerobic fitness (P = .041), upper- (P < .001) and lower-body (P < .001) strength, and triglycerides (P = .036), while preventing an increase in body fat (P = .049). Aerobic training also improved fitness (P = .052). One serious adverse event occurred in the group that performed aerobic exercise.\n In the short term, both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy. Resistance exercise generated longer-term improvements and additional benefits for QOL, strength, triglycerides, and body fat.", "Fatigue is a common and often severe problem in cancer patients undergoing chemotherapy. The authors postulated that physical activity training can reduce the intensity of fatigue in this group of patients.\n A group of cancer patients receiving high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group; n = 27) followed an exercise program during hospitalization. The program was comprised of biking on an ergometer in the supine position following an interval training pattern for 30 minutes daily. Patients in the control group (n = 32) did not train. Psychologic distress was assessed at hospital admission and discharge with the Profile of Mood States and Symptom Check List 90.\n By the time of hospital discharge, fatigue and somatic complaints had increased significantly in the control group (P for both < 0.01) but not in the training group. Furthermore, by the time of hospital discharge, the training group had a significant improvement in several scores of psychologic distress (obsessive-compulsive traits, fear, interpersonal sensitivity, and phobic anxiety) (P value for all scores < 0.05); this outcome was not observed in the control group.\n The current study found that aerobic exercise can reduce fatigue and improve psychologic distress in cancer patients undergoing chemotherapy.", "Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat.\n In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition.\n Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P =.002) and higher quality of life (P =.001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P =.009) and lower body (P <.001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds.\n Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.", "To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up.\n Pragmatic randomised controlled prospective open trial.\n Three National Health Service oncology clinics in Scotland and community exercise facilities.\n 203 women entered the study; 177 completed the six month follow-up.\n Supervised 12 week group exercise programme in addition to usual care, compared with usual care.\n Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility.\n Mixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95% confidence interval 83 to 176) for metres walked in 12 minutes, 182 (75 to 289) for minutes of moderate intensity activity reported in a week, 2.6 (1.6 to 3.7) for shoulder mobility, 2.5 (1.0 to 3.9) for breast cancer specific subscale of quality of life, and 4.0 (1.8 to 6.3) for positive mood. No significant effect was seen for general quality of life (FACT-G), which was the primary outcome. At the six month follow-up, most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged. No adverse effects were noted.\n Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later. Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services. Trial registration Current controlled trials ISRCTN12587864 [controlled-trials.com].", "To examine the effect of a progressive upper-body exercise program on lymphedema secondary to breast cancer treatment.\n Fourteen breast cancer survivors with unilateral upper extremity lymphedema were randomly assigned to an exercise (n = 7) or control group (n = 7). The exercise group followed a progressive, 8-week upper-body exercise program consisting of resistance training plus aerobic exercise using a Monark Rehab Trainer arm ergometer. Lymphedema was assessed by arm circumference and measurement of arm volume by water displacement. Patients were evaluated on five occasions over the experimental period. The Medical Outcomes Trust Short-Form 36 Survey was used to measure quality of life before and after the intervention. Significance was set at alpha < or = 0.01.\n No changes were found in arm circumference or arm volume as a result of the exercise program. Three of the quality-of-life domains showed trends toward increases in the exercise group: physical functioning (P =.050), general health (P =.048), and vitality (P =.023). Mental health increased, although not significantly, for all subjects (P =.019). Arm volume measured by water displacement was correlated with calculated arm volume (r =.973, P <.001), although the exercise and control group means were significantly different (P <.001).\n Participation in an upper-body exercise program caused no changes in arm circumference or arm volume in women with lymphedema after breast cancer, and they may have experienced an increase in quality of life. Additional studies should be done in this area to determine the optimum training program.", "To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease.\n Randomised controlled trial.\n Two university hospitals in Copenhagen, Denmark.\n 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up.\n Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care.\n European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo(2)max). Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables.\n Adjusted for baseline score, disease, and demographic covariates, the intervention group showed an estimated improvement at six weeks for the primary outcome, fatigue, of -6.6 points (95% confidence interval -12.3 to -0.9, P=0.02; effect size=0.33, 0.04 to 0.61). Significant effects were seen on vitality (effect size 0.55, 95% CI 0.27 to 0.82), physical functioning (0.37, 0.09 to 0.65), role physical (0.37, 0.10 to 0.64), role emotional (0.32, 0.05 to 0.59), and mental health (0.28, 0.02 to 0.56) scores. Improvement was noted in physical capacity: estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min (95% CI 0.1 to 0.2, P<0.0001) and for muscular strength (leg press) was 29.7 kg (23.4 to 34.9, P<0.0001). No significant effect was seen on global health status/quality of life.\n A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease. The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life.\n Current Controlled trials ISRCTN05322922.", "Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects.\n We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema.\n The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events.\n Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.", "To examine the effects of a seated exercise program on fatigue and quality of life (QOL) in women with metastatic breast cancer.\n Randomized, controlled, longitudinal trial.\n Outpatient clinic of a comprehensive cancer center.\n Convenience sample of 38 women who were beginning outpatient chemotherapy.\n Subjects were randomized to a control or intervention group; the intervention was performance of a seated exercise program using home videotape three times per week for four cycles of chemotherapy. All subjects completed the Functional Assessment of Chronic Illness Therapy Fatigue Version IV (FACIT F) at baseline and at the time of the next three cycles. Subjects were asked to document the frequency, duration, and intensity of all exercise participation on monthly calendars.\n Exercise, fatigue, and QOL.\n 32 subjects, 16 per group, completed the study follow-up. With a mixed modeling approach, total FACIT F scores for the entire sample declined at a significant rate (p = 0.003) beginning with cycle 3 but at a slower rate for the experimental group (p = 0.02). Fatigue scores indicated less increase and physical well-being subscale scores showed less decline for the experimental group (p = 0.008 and p = 0.02, respectively).\n Women with advanced breast cancer randomized to the seated exercise intervention had a slower decline in total and physical well-being and less increase in fatigue scores starting with the third cycle of chemotherapy.\n Seated exercise may be a feasible exercise program for women with advanced cancer for controlling fatigue and improving physical well-being.", "Shoulder pain and disability are well recognized complications associated with surgery for head and neck cancer. This study was designed to examine the effects of progressive resistance exercise training (PRET) on upper extremity pain and dysfunction in postsurgical head and neck cancer survivors.\n Fifty-two head and neck cancer survivors were assigned randomly to PRET (n = 27) or a standardized therapeutic exercise protocol (TP) (n = 25) for 12 weeks. The primary endpoint was change in patient-rated shoulder pain and disability from baseline to postintervention. Secondary endpoints were upper extremity strength and endurance, range of motion, fatigue, and quality of life.\n Follow-up assessment for the primary outcome was 92%, and adherence to the supervised PRET and TP programs were 95% and 87%, respectively. On the basis of intention-to-treat analyses, PRET was superior to TP for improving shoulder pain and disability (-9.6; 95% confidence interval [95% CI], -16.4 to -4.5; P = .001), upper extremity strength (+10.8 kg; 95% CI, 5.4-16.2 kg; P < .001), and upper extremity endurance (+194 repetitions x kg; 95% CI, 10-378 repetitions x kg; P = .039). Changes in neck dissection impairment, fatigue, and quality of life favored the PRET group but did not reach statistical significance.\n The PRET program significantly reduced shoulder pain and disability and improved upper extremity muscular strength and endurance in head and neck cancer survivors who had shoulder dysfunction because of spinal accessory nerve damage. Clinicians should consider the addition of PRET in the rehabilitation of postsurgical head and neck cancer survivors.\n (Copyright) 2008 American Cancer Society.", "PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidenced by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate.\n Experimental, two-group pretest, post-test.\n Two university teaching hospital outpatient radiation therapy departments.\n 46 women beginning a six-week program of radiation therapy for early stage breast cancer.\n Following random assignment, subjects in the exercise group maintained an individualized, self-paced, home-based walking exercise program throughout treatment. The control group received usual care. Dependent variables were measured prior to and at the end of radiation therapy. In addition, symptoms were assessed at the end of three weeks of treatment.\n Participation in the walking exercise program, physical functioning fatigue, emotional distress, and difficulty sleeping.\n Hypothesis testing by multivariate analysis of covariance, with pretest scores as covariates, indicated significant differences between groups on outcome measures (p < 0.001). The exercise group scored significantly higher than the usual care group on physical functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and difficulty sleeping. Fatigue was the most frequent and intense subjective symptom reported.\n A self-paced, home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy.\n Nurse-prescribed and -monitored exercise is an effective, convenient, and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment.", "Physical activity provides a number of physical and psychological benefits to cancer survivors, including lessening the impact of detrimental cancer-related symptoms and treatment side-effects (e.g. fatigue, nausea), and improving overall well-being and quality of life. The purpose of the present pilot study was to examine the physical and psychological benefits afforded by a 7-week yoga program for cancer survivors.\n Eligible participants (per-screened with PAR-Q/PAR-MED-X) were randomly assigned to either the intervention (n=20) or control group (n=18). All participants completed pre- and post-testing assessments immediately before and after the yoga program, respectively.\n The yoga program participants (M age=51.18 (10.33); 92% female) included primarily breast cancer survivors, on average 55.95 (54.39) months post-diagnosis. Significant differences between the intervention and the control group at post-intervention were seen only in psychosocial (i.e. global quality of life, emotional function, and diarrhea) variables (all p's <0.05). There were also trends for group differences, in the hypothesized directions, for the psychosocial variables of emotional irritability, gastrointestinal symptoms, cognitive disorganization, mood disturbance, tension, depression, and confusion (all p's <0.10). Finally, there were also significant improvements in both the program participants and the controls from pre- to post-intervention on a number of physical fitness variables.\n These initial findings suggest that yoga has significant potential and should be further explored as a beneficial physical activity option for cancer survivors. Future research might attempt to include a broader range of participants (e.g. other types of cancer diagnoses, male subjects), a larger sample size, and a longer program duration in an RCT.", "To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy.\n Experimental.\n Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs.\n 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment.\n Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion.\n Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety).\n Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program.\n Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy.\n Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.", "Few randomized controlled trials have examined the effects of combined aerobic and resistance training in breast cancer survivors soon after completing adjuvant therapy. Breast cancer survivors (N=58) within 2 years of completing adjuvant therapy were randomly assigned to an immediate exercise group (IEG; n=29) or a delayed exercise group (DEG; n=29). The IEG completed 12 weeks of supervised aerobic and resistance exercise, three times per week. The DEG completed the program during the next 12 weeks. Participants completed patient-rated outcomes at baseline, 6, 12, 18 and 24 weeks. The primary endpoint was overall quality of life (QoL) measured by the Functional Assessment of Cancer Therapy-Breast scale. Secondary endpoints were fatigue, social physique anxiety, and physical fitness. Follow-up data was obtained on 97% of participants and exercise adherence was 61.3%. Repeated measures analyses of variance revealed a significant group by time interaction for overall QoL (P<0.001). Specifically, QoL increased in the IEG from baseline to 12 weeks by 20.8 points compared to a decrease in the DEG of 5.3 points (mean group difference=26.1; 95% CI=18.3-32.7; P<0.001). From 12 to 24 weeks, QoL increased in the DEG by 29.5 points compared to an increase of 6.5 points in the IEG (mean group difference=23.0; 95% CI=16.3-29.1; P<0.001). Similar results were obtained for the secondary endpoints. Combined aerobic and resistance exercise soon after the completion of breast cancer therapy produces large and rapid improvements in health-related outcomes.", "Fatigue and insomnia are problems for patients with cancer. Research findings show that aerobic exercise decreases cancer-related fatigue. Because patients with cancer who have skeletal muscle wasting may not obtain maximum benefit from aerobic exercise training, exercise programs may need to include resistance training. Thus far, testing exercise as an intervention for fatigue has focused on patients with breast cancer and excluded patients with bone metastasis. There is a need to test the feasibility and effectiveness of exercise for patients with other types of cancer and with bone involvement. The effect of aerobic and strength resistance training on the sleep of patients with cancer has not been tested. A pilot/feasibility study with a randomized controlled design was conducted to investigate home-based exercise therapy for 24 patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation as treatment for multiple myeloma. None of the patients injured themselves. Because of the small sample size in the feasibility study, the effect of exercise on lean body weight was the only end point that obtained statistical significance. However, the results suggest that an individualized exercise program for patients receiving aggressive treatment for multiple myeloma is feasible and may be effective for decreasing fatigue and mood disturbance, and for improving sleep.", "Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients.\n One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially.\n Regression analysis indicated that the MQ group significantly improved overall QOL (t(144) = -5.761, P < 0.001), fatigue (t(153) = -5.621, P < 0.001), mood disturbance (t(122) =2.346, P = 0.021) and inflammation (CRP) (t(99) = 2.042, P < 0.044) compared with usual care after controlling for baseline variables.\n This study indicates that MQ can improve cancer patients' overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation." ]

[ "12907008", "15794968", "10749457", "12352800", "19483514", "14523142", "11172176", "15844075", "14557958", "16940833" ]

[ "Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial.", "Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.", "Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group.", "Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia.", "Efficacy of an 11-valent pneumococcal conjugate vaccine against radiologically confirmed pneumonia among children less than 2 years of age in the Philippines: a randomized, double-blind, placebo-controlled trial.", "A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection.", "Efficacy of a pneumococcal conjugate vaccine against acute otitis media.", "The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children.", "Protective efficacy of a second pneumococcal conjugate vaccine against pneumococcal acute otitis media in infants and children: randomized, controlled trial of a 7-valent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine in 1666 children.", "Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs." ]

[ "Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease.\n In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrollment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol.\n 8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76.8% (95% CI -9.4% to 95.1%) and the intention-to-treat total primary efficacy was 82.6% (21.4% to 96.1%).\n PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.", "Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children.\n We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat.\n 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo.\n In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.", "To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media.\n The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37,868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears.\n In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%.\n This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.", "To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children.\n The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity.\n The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group.\n The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.", "Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV on childhood pneumonia.\n We conducted a randomized, placebo-controlled, double-blind trial in Bohol, the Philippines (ISRCTN 62323832). Children 6 weeks to <6 months of age were randomly allocated to receive 3 doses of either an 11-valent PCV (11PCV, sanofi pasteur, Lyon, France) or a saline placebo, with a minimum interval of 4 weeks between doses to determine vaccine efficacy (VE) against the primary outcome of a child experiencing first episode of community-acquired radiologically defined pneumonia in the first 2 years of life. Secondary end points were clinical pneumonia, IPD, safety, and immunogenicity.\n Twelve thousand one hundred ninety-one children were enrolled. By per protocol (PP) analysis, 93 of 6013 fully vaccinated 11PCV recipient children had a first episode of radiologic pneumonia compared with 120 of 6018 placebo recipients. VE against radiologically defined pneumonia for the PP cohort of children 3 to 23 months old was 22.9% (95% CI: -1.1, 41.2; P = 0.06), for the prespecified subgroups of children 3 to 11 months of age, 34.0% (95% CI: 4.8, 54.3; P = 0.02), and of those 12 to 23 months old, 2.7% (95% CI: -43.5, 34.0; P = 0.88). By intent-to-treat (ITT) analysis, 119 of 6097 11PCV recipient children had an episode of radiologic pneumonia compared with 141 of 6094 placebo recipients. VE against radiologic pneumonia for the ITT cohort of children <2 years old was 16.0% (95% CI -7.3, 34.2; P = 0.16), for a subgroup of children <12 months of age, 19.8% (95% CI: -8.8, 40.8; P = 0.15). VE against clinical pneumonia by PP was not significant (VE 0.1%; 95% CI -9.4, 8.7; P = 0.99). IPD was rare: only 3 cases of IPD due to vaccine serotypes were observed during the study. 11PCV was immunogenic and well tolerated. Among 11PCV recipients, a small excess of serious adverse respiratory events was observed in the first 28 days after the first and second dose of vaccine, and of nonrespiratory events after the first dose. An excess of pneumonia episodes in 11PCV recipients in the month following the second dose of vaccination was the principal reason for lower VE by ITT analysis than by PP analysis.\n In PP analysis, a 22.9% reduction of community-acquired radiologically confirmed pneumonia in children younger than 2 years of age in the 11-valent tetanus-diphtheria toxoid-conjugated PCV vaccinated group was observed; a reduction similar as observed in other PCV trials. We could not demonstrate any VE against clinical pneumonia. Our finding confirms for the first time that in a low-income, low-mortality developing country in Asia, at least one-fifth of radiologically confirmed pneumonia is caused by pneumococcus, and thus preventable by PCV. Whether PCV should be included in national program in such settings, however, depends on careful country specific disease burden measurement and cost-effectiveness calculation.", "Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa.\n At 6, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo. All children received Haemophilus influenzae type b conjugate vaccine. Efficacy and safety were analyzed according to the intention-to-treat principle.\n Among children without human immunodeficiency virus (HIV) infection, the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent (95 percent confidence interval, 39 to 97; 17 cases among controls and 3 among vaccine recipients). Among HIV-infected children, the efficacy was 65 percent (95 percent confidence interval, 24 to 86; 26 and 9 cases, respectively). Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children). The incidence of invasive pneumococcal disease caused by penicillin-resistant strains was reduced by 67 percent (95 percent confidence interval, 19 to 88; 21 cases in the control group and 7 in the vaccinated group), and that caused by strains resistant to trimethoprim-sulfamethoxazole was reduced by 56 percent (95 percent confidence interval, 16 to 78; 32 and 14 cases, respectively).\n Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia. The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection.\n Copyright 2003 Massachusetts Medical Society", "Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae.\n We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy.\n Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent.\n The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.", "Pneumococcal conjugate vaccine (PnCV) may be used as a probe to define the burden of pneumococcal disease and better characterize the clinical presentation of pneumococcal pneumonia.\n This study used a 9-valent PnCV to define different end points of vaccine efficacy and the preventable burden of pneumococcal pneumonia in 39,836 children who were randomized in a double-blind, placebo-controlled trial in South Africa.\n Whereas the point-estimate of vaccine efficacy was greatest when measured against the outcome of vaccine-serotype specific pneumococcal bacteremic pneumonia (61%; P = .01), the sensitivity of blood culture to measure the burden of pneumococcal pneumonia prevented by vaccination was only 2.6% in human immunodeficiency virus (HIV)-uninfected children and 18.8% in HIV-infected children. Only 37.8% of cases of pneumococcal pneumonia prevented by PnCV were detected by means of chest radiographs showing alveolar consolidation. A clinical diagnosis of pneumonia provided the best estimate of the burden of pneumococcal pneumonia prevented through vaccination in HIV-uninfected children (267 cases prevented per 100,000 child-years) and HIV-infected children (2573 cases prevented per 100,000 child-years).\n Although outcome measures with high specificity, such as bacteremic pneumococcal pneumonia, provide a better estimate as to vaccine efficacy, the burden of disease prevented by vaccination is best evaluated using outcome measures with high sensitivity, such as a clinical diagnosis of pneumonia.", "To assess the efficacy of a 7-valent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PncOMPC) against acute otitis media (AOM), 1666 infants were randomly assigned to receive either PncOMPC or control vaccine (hepatitis B vaccine) at 2, 4, 6, and 12 months of age. Of the 835 children assigned to receive PncOMPC, 187 received a 23-valent pneumococcal polysaccharide vaccine (PncPS) at 12 months of age instead. Whenever AOM was diagnosed, middle ear fluid was aspirated for bacterial culture. In the PncOMPC and control groups, there were 110 and 250 AOM episodes, respectively, in children between 6.5 and 24 months of age that could be attributed to vaccine serotypes, which indicates a vaccine efficacy of 56% (95% confidence interval, 44%-66%). The serotype-specific efficacy ranged from 37% for 19F to 82% for 9V. The 2 boosters seemed to provide equal protection against AOM, but PncPS induced markedly higher antibody concentrations. The efficacy of PncOMPC was comparable to that of the recently licensed pneumococcal conjugate vaccine.", "A World Health Organization (WHO) working group in 2001 developed a method for standardizing interpretation of chest radiographs in children for epidemiologic purposes. We reevaluated radiographs from the Kaiser Permanente Pneumococcal Efficacy trial using this method.\n Seven-valent pneumococcal conjugate vaccine was evaluated in a randomized, controlled study including 37,868 infants. Effectiveness against pneumonia was previously evaluated using the original treating radiologist reading. There were 2841 sets of radiographs from this trial and all available radiographs were scanned and read blindly by 2 WHO crosstrained readers (A and B); discordance between the 2 primary readers was resolved through a consensus reading by an adjudicating panel of 2 radiologists.\n Of the 2841 radiographs, 2446 were available for scanning and were reviewed using WHO-defined descriptive categories. Two hundred fifty of the 2446 radiographs were read as positive by both readers. An additional 129 were read as positive by reader A only and 142 by reader B only for a total of 521 radiographs that were read as positive by one or both of the reviewers. The concordance rate between the 2 reviewers was 250 of 521 (48%). Of the 271 discordant radiographs, 45 of 129 (34.9%) of reader A and 66 of 142 (46.5%) for reader B were finalized as positive by the adjudicating panel. Overall, 361 radiographs were finalized as positive (12.7%). With these 361 images as the standard, the sensitivity and specificity of reader A were 82% and 97%, respectively, and for reader B, 88% and 97%, respectively. Kappa between the 2 readers was 0.58. Of 25 control radiographs read as positive by both A and B, 80% were also read as positive by the panel and all 25 control negative radiographs were read as negative by the panel. Using original readings by point-of-care radiologists, efficacy against first episode of radiograph confirmed pneumonia was 17.7% (95% confidence interval [CI] = 4.8-28.9%) in intent-to-treat and 20.5% (95% CI = 4.4-34%) in per protocol. Using the WHO method, the efficacy against first episode of radiograph confirmed pneumonia adjusting for age, gender and year of vaccination of 25.5% (95% CI = 6.5-40.7%, P = 0.011) for intent-to-treat and 30.3% (95% CI = 10.7-45.7%, P = 0.0043) for per protocol.\n Using WHO criteria for reading of radiographs increased point estimates of vaccine efficacy presumably as a result of improved specificity." ]

[ "8239224", "1747702" ]

[ "Hydroxychloroquine compared with placebo in rheumatoid arthritis. A randomized controlled trial.", "Should disease-modifying agents be used in mild rheumatoid arthritis?" ]

[ "To assess the efficacy of hydroxychloroquine, 400 mg daily, for rheumatoid arthritis.\n Six-month, double-blind, randomized trial.\n Ambulatory referral clinic in a Mexico City, Mexico, teaching hospital.\n A total of 126 patients with early rheumatoid arthritis were randomly assigned to receive hydroxychloroquine, 400 mg/d, or placebo; 121 patients completed the study.\n Hydroxychloroquine showed a clinically and statistically significant improvement over placebo in joint score (20% greater mean improvement; 10% more patients improved by > 50%); pain (40% greater mean improvement; 19% more patients improved by > 50%); grip strength (22% greater mean improvement; 21% more patients improved by > 50%); patient global assessment (16% more patients stated they had improved); and physician global assessment (12% more patients were judged to have improved). Side effects were mild, and no patients in the hydroxychloroquine group required discontinuation of therapy. Patient compliance with the study medication was high.\n Hydroxychloroquine is moderately effective in early rheumatoid arthritis.", "A 12-month double-blind controlled study comparing hydroxychloroquine 400 mg daily with placebo in 104 patients with mild RA was conducted to see whether patients with mild rheumatoid arthritis (RA) benefit from treatment with disease-modifying agents. Mild RA was defined as synovitis limited to the hands and feet, an ESR less than 30 mm/h and C-reactive protein less than 20 mg/l, a situation where accepted clinical practice is to use a non-steroidal anti-inflammatory agent alone. By 6 months, the improvement of clinical and laboratory parameters in the hydroxychloroquine treated patients was significant compared with pretreatment levels and significantly greater than the control group. This improvement was maintained at 12 months. In addition, fewer patients withdrew through lack of efficacy, eight on hydroxychloroquine versus 18 on placebo. The implications of treating this well defined group of patients is discussed." ]

[ "11242179", "10232312", "10232311", "3257532" ]

[ "Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal.", "Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.", "Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group.", "Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS." ]

[ "To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.\n Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.\n Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.\n Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).\n Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.", "There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality.\n Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital.\n Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group.\n In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.", "In sub-Saharan Africa, various bacterial diseases occur before pneumocystosis or toxoplasmosis in the course of HIV-1 infection, and are major causes of morbidity and mortality. We did a randomised, double blind, placebo-controlled clinical trial at community-health centres in Abidjan, Côte d'Ivoire, to assess the efficacy of trimethoprim-sulphamethoxazole (co-trimoxazole) chemoprophylaxis at early stages of HIV-1 infection.\n 843 HIV-infected patients were screened and 545 enrolled in the study. Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo. The primary outcome was the occurrence of severe clinical events, defined as death or hospital admission irrespective of the cause. Analyses were by intention to treat.\n Four of the randomised patients were excluded (positive for HIV-2 only). 120 severe events occurred among 271 patients in the co-trimoxazole group and 198 among 270 in the placebo group. Significantly fewer patients in the co-trimoxazole group than in the placebo group had at least one severe event (84 vs 124); the probability of remaining free of severe events was 63.7% versus 45.8% (hazard ratio 0.57 [95% CI 0.43-0.75], p=0.0001) and the benefit was apparent in all subgroups of initial CD4-cell count. Survival did not differ between the groups (41 vs 46 deaths, p=0.51). Co-trimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients (vs 26 in the placebo group).\n Patients who might benefit from co-trimoxazole could be recruited on clinical criteria in community clinics without knowing the patients CD4-cell count. This affordable measure will enable quick public-health intervention, while monitoring bacterial susceptibility and haematological tolerance.", "The safety and efficacy of sulfamethoxazole and trimethoprim in the prevention of Pneumocystis carinii pneumonia associated with the acquired immunodeficiency syndrome (AIDS) were evaluated. Sixty patients with a new diagnosis of Kaposi's sarcoma and no history of opportunistic infections were randomly assigned to receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice per day or no therapy. None of the 30 patients receiving sulfamethoxazole and trimethoprim developed P carinii pneumonia. Sixteen of the 30 patients receiving no suppressive therapy developed P carinii pneumonia. Development of P carinii pneumonia was associated with the stage of Kaposi's sarcoma, B subtype disease, and the presence of 0.20 X 10(9)/L (200/mm3) or fewer CD4 cells at study entry. The proportion of patients surviving and the mean length of survival were significantly greater in the treatment group compared with the control group. Adverse reactions occurred in 15 patients (50%)." ]

[ "11868007", "8200551", "10205211", "1884968", "2209496", "8406150", "15278040", "8224679", "1955161", "9158465", "8780566", "9869717", "16650535", "8228078" ]

[ "Epinephrine versus epinephrine plus fibrin glue injection in peptic ulcer bleeding: a prospective randomized trial.", "Endoscopic injection therapy for bleeding peptic ulcer; a comparison of adrenaline alone with adrenaline plus ethanolamine oleate.", "Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding.", "Endoscopic hemostasis of bleeding peptic ulcers: 1:10000 adrenalin injection vs. 1:10000 adrenalin +1% aethoxysclerol injection vs. heater probe.", "Injection therapy of bleeding peptic ulcer. A prospective, randomized trial using epinephrine and thrombin.", "Is sclerosant injection mandatory after an epinephrine injection for arrest of peptic ulcer haemorrhage? A prospective, randomised, comparative study.", "A prospective, randomized trial comparing mechanical methods of hemostasis plus epinephrine injection to epinephrine injection alone for bleeding peptic ulcer.", "Adding a sclerosant to endoscopic epinephrine injection in actively bleeding ulcers: a randomized trial.", "Endoscopic treatment for bleeding peptic ulcers: randomised comparison of adrenaline injection and adrenaline injection + Nd:YAG laser photocoagulation.", "Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers.", "Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin.", "Comparison of the hemostatic efficacy of the endoscopic hemoclip method with hypertonic saline-epinephrine injection and a combination of the two for the management of bleeding peptic ulcers.", "Comparison of hemostatic efficacy for epinephrine injection alone and injection combined with hemoclip therapy in treating high-risk bleeding ulcers.", "Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol." ]

[ "Peptic ulcer bleeding remains a disease with considerable morbidity and mortality. Epinephrine is the most widely used endoscopic injection agent, but bleeding recurs in 20% of high-risk cases. Fibrin glue might be an ideal injection agent, based on its physiologic properties, despite its demanding injection technique and high cost. The aim of this study was to determine whether the injection of fibrin glue in combination with epinephrine improves outcome for patients at high risk of recurrent bleeding.\n Patients were prospectively randomized to injection of epinephrine alone (n = 70) or epinephrine plus fibrin glue (n = 65). Endoscopy was repeated daily until the ulcer base was clean. All patients were treated with high-dose omeprazole.\n Initial hemostasis was 100% in both groups. There was no significant overall difference in rates of recurrent bleeding (24.3% and 21.5%, respectively, for epinephrine and epinephrine plus fibrin). When patients were stratified according to Forrest criteria, no significant difference could be found, although there was a trend toward less recurrent bleeding after fibrin injection of actively bleeding ulcers. There was no significant difference in the proportions of patients who required surgery (10% and 6%, respectively, for epinephrine and epinephrine plus fibrin). Mortality was the same (3%) in each group.\n Adding fibrin glue to epinephrine for injection treatment of bleeding peptic ulcers does not improve outcome. Fibrin glue might be of some value in selected cases.", "One hundred and seven consecutive patients presenting with significant peptic ulcer haemorrhage were randomised to endoscopic injection with 3-10 ml of 1:100,000 adrenaline (55 patients, group 1) or to a combination of adrenaline and 5% ethanolamine (52 patients, group 2). All had major stigmata of haemorrhage and endoscopic injection was undertaken by a single endoscopist. The groups were well matched with regard to risk factors. Rebleeding occurred in eight of the group 1 patients and seven in the group 2 patients; surgical operation rates, median blood transfusion requirements, and hospital stay were similar in both groups. The efficacy of either form of injection was similar whether patients presented with active bleeding or a non-bleeding visible vessel. No complications occurred. In patients presenting with significant peptic ulcer bleeding, the addition of a sclerosant confers no advantage over injection with adrenaline alone.", "Peptic ulcers with active bleeding or a non-bleeding visible vessel require aggressive endoscopic treatment.\n To determine whether endoscopic adrenaline injection alone or contact probe therapy following injection is a suitable treatment for peptic ulcer bleeding.\n A total of 96 patients with active bleeding or non-bleeding visible vessels received adrenaline alone, bipolar electrocoagulation alone, or combined treatment (n=32 in each group).\n Initial haemostasis was not achieved in one patient in the adrenaline group, two in the gold probe group, and two in the injection gold probe group (p>0.1). Rebleeding episodes were fewer in the injection gold probe group (2/30, 6.7%) than in the gold probe group (9/30, 30%, p=0.04) and in the adrenaline group (11/31, 35.5%, p=0.01). Treatment failure (other therapy required) was rarer in the injection gold probe group (4/32, 12.5%) than in the adrenaline group (12/32, 37.5%, p=0.04). The volume of blood transfused after entry of the study was less in the injection gold probe group (mean 491 ml) than in the adrenaline group (1548 ml, p<0. 0001) and the gold probe group (1105 ml, p<0.01). Duration of hospital stay, numbers of patients requiring urgent surgery, and death rate were not statistically different among the three groups.\n For patients with peptic ulcer bleeding, combined adrenaline injection and gold probe treatment offers an advantage in preventing rebleeding and decreasing the need for blood transfusion.", "To evaluate the efficacy of three endoscopic methods which utilize different mechanisms of hemostasis to control bleeding peptic ulcers, we performed a prospective randomized study in 83 patients. Thirty-two patients were treated with 1:10000 adrenalin (Group I), 29 patients with 1:10000 adrenalin +1% aethoxysclerol (Group II), and 22 patients with the heater probe (Group III). Gastric ulcers were the source of bleeding in 14, 15 and 12 patients while duodenal ulcers were the source in 16, 13 and 10 patients in Groups I, II and III, respectively. Two stomal ulcers were noted in Group I and 1 in Group II. Two spurters were treated in Group I and 4 in Group II, while 22, 13 and 10 oozers were treated in Groups I, II and III, respectively. Definitive hemostasis was achieved in 94%, 100% and 95% in Groups I, II and III, respectively while the rebleeding rate was 6.25%, 6.9% and 9% respectively. 1:10000 adrenalin injection alone or when combined with subsequent instillation of a sclerosing agent and heater probe application have comparable efficacy in the endoscopic control of bleeding peptic ulcers.", "A prospective randomized trial involving 64 patients with bleeding peptic ulcers was performed to assess the efficacy of two modalities of injection therapy. The inclusion criterion was the presence of active bleeding or a visible vessel at emergency endoscopy. Thirty-two patients were treated with epinephrine (Group A) and 32 with epinephrine plus thrombin (Group B). Permanent hemostasis was achieved in 81.3% Group A, and 84.4% Group B patients, and therapy failures occurred in 18.6% and 15.6%, respectively. Mortality was nil in both groups. There were no differences in the requirement for emergency surgery, or in the number of transfusions in the two groups. A second elective endoscopy was performed in 49 patients between the 3rd and the 5th day after admission, proceeding to a second injection therapy if a visible vessel was still seen. There were no failures among re-injected patients. With one exception, none of the failures occurred in patients in whom a second endoscopy was done. Our results suggest that injection therapy, which is a simple technique, should be considered as the initial treatment of choice in bleeding peptic ulcer. The addition of thrombin to epinephrine does not improve the results of the method. An early second endoscopy and local therapy if a visible vessel is still present, may further improve the results.", "A prospective, randomised, comparative study was performed to assess the need for a pure alcohol injection after an epinephrine injection in the arrest of active peptic ulcer bleeding. Sixty four patients with active ulcer bleeding were enrolled in the study. The two groups (epinephrine and epinephrine plus pure alcohol) were matched for sex, age, site of bleed, endoscopic findings, shock, haemoglobin, and concomitant illness at randomisation. The volume of injected epinephrine in the epinephrine and the epinephrine plus pure alcohol groups mean (SD) was 6.0 (3.0) ml and 5.5 (3.0) ml respectively (p > 0.05). The volume of injected pure alcohol in the epinephrine plus pure alcohol group was 1.9 (1.1) ml. Bleeding was initially controlled in 31 (97%) of the epinephrine group and all of the epinephrine plus pure alcohol group. Rebleeding occurred in 11 (36%) of the epinephrine group and in five (16%) of the epinephrine plus pure alcohol group (p > 0.05). Rebleeding was successfully controlled in some patients with treatment by a second injection. Other patients had heat probe thermocoagulation or surgery. Ultimate haemostatic rates were 69% (22/32) and 88% (28/32) for the epinephrine and the epinephrine plus pure alcohol groups respectively (p > 0.05). The epinephrine plus pure alcohol group achieved a better haemostatic effect for spurting haemorrhage (9/10 v 5/11, p < 0.05). The need for emergency operations and blood transfusions were comparable in both groups. The stay in hospital were less in the epinephrine plus pure alcohol group (mean 4.3 v 7.1, p < 0.05). It is concluded that pure alcohol injection after an epinephrine injection can improve the haemostatic rate in patients with spurting haemorrhage and shorten the hospital stay for patients with active bleeding.", "The hemostatic efficacy of mechanical methods of hemostasis, together with epinephrine injection, was compared with that of epinephrine injection alone in bleeding peptic ulcer.\n Ninety patients with a peptic ulcer with active bleeding or a non-bleeding visible vessel were randomly assigned to undergo a mechanical method of hemostasis (23 hemoclip application, 22 band ligation) plus epinephrine injection, or epinephrine injection alone.\n The two groups were similar with respect to all background variables. Initial hemostasis was achieved in 44/45 (97.8%) patients in both groups. The mean number of hemoclips and elastic bands applied were 2.8: 95% CI[2.5, 3.1] and 1.1: 95% CI[1.0, 1.2], respectively, and the mean volume of epinephrine injected was 19.9 mL: 95% CI[19.3 mL, 20.5 mL]. The rate of recurrent bleeding in the combination group (2/44, 4.5%) was significantly lower in comparison with the injection group (9/44, 20.5%, p < 0.05). The mean number of therapeutic endoscopic sessions needed to achieve permanent hemostasis in the combination group (1.04: 95% CI[1.01, 1.07]) was significantly lower vs. the injection group (1.22: 95% CI[1.15, 1.30]).\n The combination of an endoscopic mechanical method of hemostasis plus epinephrine injection is more effective than epinephrine injection alone for the treatment of bleeding peptic ulcer.", "We compared the efficacy of epinephrine injection and epinephrine injection followed by sodium tetradecyl sulfate in controlling active ulcer bleeding. Out of 2814 patients who underwent endoscopy for gastrointestinal bleeding, 200 patients with actively bleeding ulcers seen at the time of endoscopy were randomized to receive epinephrine injection alone (99 patients) or epinephrine injection followed by 3% sodium tetradecyl sulfate (101 patients). After the procedure the patients were transferred to the surgical gastroenterology ward and were treated by surgeons who were unaware of the mode of treatment. The patients underwent routine endoscopy 24 hours later, and epinephrine injection was repeated if active bleeding was seen again. Emergency surgery was performed for the following: (1) arterial spurting not controlled endoscopically, (2) failure of the blood pressure or pulse to stabilize after 4 units of blood, (3) total transfusion of more than 8 units of blood, or (4) rebleeding as defined by hematemesis with pulse greater than 100 beats/min or blood pressure less than 100 mm Hg after stabilization. The two groups were comparable in age, sex, site of ulcer, and severity of bleeding. Initial hemostasis was obtained at the time of endoscopy in 94% of the epinephrine group and 97% of the epinephrine plus sodium tetradecyl sulfate group. No difference in outcome was seen in the two groups as measured by emergency surgery requirement, blood transfusion, hospital stay, and hospital mortality. Endoscopic epinephrine injection is effective in controlling active ulcer bleeding. The additional injection of sodium tetradecyl sulfate confers no additional advantage.", "Forty two patients with haemorrhage from peptic ulcers with visible vessels were enrolled in a randomised study comparing endoscopic haemostasis with adrenaline (1:10,000) injections (adrenaline group) and adrenaline injection + neodymium yttrium-aluminium-garnet (Nd:YAG) laser photocoagulation (adrenaline + laser group). The two groups (21 patients each) were well matched for factors affecting outcome. Surgery was performed for continued haemorrhage uncontrolled by endoscopic treatment or rebleeding after two endoscopic treatments. Haemostasis after one treatment was similar in the two groups: adrenaline 16/21 (76%), adrenaline + laser 18/21 (86%). Haemostasis after two treatments was numerically (0.05 less than p less than 0.10) greater in the adrenaline + laser group: 21/21 (100%) v 18/21 (86%). Three patients (14%) in the adrenaline group underwent uneventful emergency surgery. There were no deaths or procedure related complications in either group. Most bleeds from peptic ulcers with visible vessels can be controlled endoscopically without the need for surgery. Both treatments in this study proved highly efficacious in securing haemostasis. Adrenaline injection treatment seems to be the treatment of choice in view of its simplicity, low cost, and availability. Additional Nd:YAG laser treatment may provide a marginal improvement in efficacy, although a much larger trial would be required to prove this.", "To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers.\n Randomised prospective study of patients admitted with actively bleeding peptic ulcers.\n One university hospital.\n 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment.\n Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital.\n Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01).\n The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage.", "Endoscopic injection therapy improves outcome in bleeding peptic ulcer, but the optimum regimen is unknown. The aim of this study was to compare the efficacy of endoscopic therapy with dilute adrenaline alone vs. adrenaline plus human thrombin in the treatment of patients with major peptic ulcer hemorrhage.\n One hundred forty patients with significant peptic ulcer hemorrhage and active arterial bleeding or a nonbleeding visible vessel were randomized to endoscopic injection with 1:100,000 adrenaline (70 patients; group 1) or to adrenaline plus 600-1000 IU of human thrombin (70 patients; group 2). The two groups were well matched for age, shock, hemoglobin concentration, comorbid disease, endoscopic findings, and consumption of nonsteroidal anti-inflammatory drugs.\n Fourteen patients from group 1 (20%) and 3 patients from group 2 (4.5%) rebled (P < 0.005). Seven patients from group 1 (10%) but no patients from group 2 died within 30 days of admission (P < 0.013). Patients from group 1 were administered a total of 297 units of blood compared with 219 units in group 2 (P < 0.041).\n Endoscopic injection using adrenaline plus human thrombin is superior to injection with dilute adrenaline alone and may represent the best treatment for bleeding peptic ulcers.", "The endoscopic hemoclip method is a safe and effective hemostatic method for managing bleeding peptic ulcers. We compared the hemostatic efficacy of the endoscopic hemoclip method with that of hypertonic saline-epinephrine (HSE) injection and a combined method in the management of bleeding peptic ulcers.\n From July 1994 to July 1997, we conducted a randomized clinical trial of endoscopic hemostasis involving 124 patients with actively bleeding or visible vessels at endoscopic inspection.\n Patients were randomly assigned to hemoclip (41 patients), HSE (41 patients), and combined treatment groups (42 patients). Initial hemostasis was achieved in 97.6%, 95.1%, and 97.6% of cases, respectively. Recurrent bleeding developed in 2.4%, 14.6%, and 9.5% of cases. Emergency operations were performed in 4.9%, 14.6%, and 2.3% of cases. The hemostasis rate was 71.4%, 50%, and 66.7% for spurting hemorrhage in each group. Permanent hemostasis was achieved in 95.1%, 85.4%, and 95.2% of cases. Three patients had complications, all in the HSE group.\n The hemoclip method is an effective hemostatic procedure and is safer than HSE injection. The combined method does not provide substantial advantage over use of the hemoclip method alone in the hemostatic management of bleeding peptic ulcers.", "Rebleeding occurs in 10% to 30% of bleeding ulcer patients receiving endoscopic epinephrine injection therapy. It remains unclear whether addition of a secondary clip therapy following epinephrine injection may reduce the rebleeding rate of high-risk bleeding ulcers.\n To compare the efficacies of epinephrine injection alone and epinephrine injection combined with hemoclip therapy in treating high-risk bleeding ulcers.\n Prospective randomized controlled trial.\n A medical center in Taiwan.\n One hundred five bleeding ulcer patients with active spurting, oozing, nonbleeding visible vessels or adherent clots in ulcer bases.\n Endoscopic combination therapy (n = 52) or diluted epinephrine injection alone (n = 53).\n Initial hemostasis rates and recurrent bleeding rates.\n Initial hemostasis was achieved in 51 patients treated with combination therapy and 49 patients with epinephrine injection therapy (98% vs 92%, P = .18). Bleeding recurred in 2 patients in the combination therapy group and 11 patients in the epinephrine injection group (3.8% vs 21%, P = .008). Among the patients with rebleeding, repeated combination therapy was more effective than repeated injection therapy in achieving permanent hemostasis (100% vs 33%, P = .02). No patient required an emergency operation in the combination therapy group. However, 5 patients in the epinephrine injection group underwent emergency surgery to arrest bleeding (0% vs 9%, P = .023).\n Treatment outcome of endoscopic hemoclip therapy is related to the techniques of endoscopists.\n Endoscopic combination therapy is superior to epinephrine injection alone in the treatment of high-risk bleeding ulcers.", "In a prospective randomized trial involving 63 patients with bleeding peptic ulcer, we assessed whether the addition of 1% polidocanol improved the results achieved by 1/10(4) adrenaline alone for injection therapy. The inclusion criterion was the presence of active arterial bleeding or a nonbleeding visible vessel at emergency endoscopy. Thirty patients were treated with 1/10(4) adrenaline (group A) and 33 with adrenaline plus 1% polidocanol (group B). Initial hemostasis was achieved in 97% of cases in both groups and permanent hemostasis in 87% patients in group A and in 76% in group B (p = NS). Mortality was 6% in group A and 3% in group B. There were no differences between the two groups regarding requirements for emergency surgery, the number of transfusions, or the length of hospital stay. One patient in group B had a perforation. No other relevant complications were noted. In conclusion, combined therapy does not improve the results achieved with adrenaline alone." ]

[ "12735675", "16635085", "9113940", "8520751", "8756801", "17629923", "8575574", "10069876", "9500751", "11704584", "7921429", "14730657", "11207020", "7644775", "18462564", "10856143", "16449264", "16701989", "16095144", "16455831", "12357478", "17046300", "10653049", "7583864", "17137405", "11529282", "12200524", "9227720", "10339734", "10373134", "16490581", "15702819", "16925692", "12693793", "9358137" ]

[ "Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma.", "Efficacy and safety of high-dose budesonide/formoterol (Symbicort) compared with budesonide administered either concomitantly with formoterol or alone in patients with persistent symptomatic asthma.", "Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment.", "Long-term circadian effects of salmeterol in asthmatic children treated with inhaled corticosteroids.", "A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma.", "Comparison of the effects of salmeterol/fluticasone propionate with fluticasone propionate on airway physiology in adults with mild persistent asthma.", "Salmeterol xinafoate in asthmatic patients under consideration for maintenance oral corticosteroid therapy. UK Study Group.", "Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group.", "Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids. Salmeterol Quality of Life Study Group.", "Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial.", "Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics.", "Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma.", "Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma.", "Pilgrim's progress: the effect of salmeterol in older children with chronic severe asthma.", "Asthma exacerbations in African Americans treated for 1 year with combination fluticasone propionate and salmeterol or fluticasone propionate alone.", "Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial.", "Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma.", "Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma.", "The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma.", "Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.", "Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma.", "A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma.", "Salmeterol/fluticasone propionate (50/500 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma.", "Salmeterol xinafoate in children on high dose inhaled steroids.", "Efficacy and safety of budesonide and formoterol in one pressurised metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial.", "Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone.", "Early asthma control and maintenance with eformoterol following reduction of inhaled corticosteroid dose.", "Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.", "Addition of inhaled salmeterol to inhaled corticosteroids in patients with poorly controlled nocturnal asthma.", "Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial.", "Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: a randomized, double-blind, placebo-controlled, 12-week study.", "Effect of fluticasone/salmeterol administered via a single device on exercise-induced bronchospasm in patients with persistent asthma.", "Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.", "Once-daily budesonide/formoterol in a single inhaler in adults with moderate persistent asthma.", "Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group." ]

[ "This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.", "Budesonide/formoterol 160/4.5 microg, two inhalations bd, is an effective and well-tolerated maintenance therapy for patients not controlled on inhaled corticosteroids alone. The authors assessed the efficacy and safety of a higher dose of budesonide/formoterol in patients with persistent symptomatic asthma.\n This was a 24-week, double-blind, double-dummy randomized study. Budesonide/formoterol 320/9 microg, two inhalations bd (1280/36 microg/day), was compared with corresponding doses of budesonide during weeks 1-12 and budesonide plus formoterol via separate inhalers during weeks 1-24. Efficacy was assessed during weeks 1-12; the primary variable was morning PEF. Safety was assessed over weeks 1-24.\n Patients (n=456; aged 12-79 years) had a mean reversibility in FEV1 of 28% and mean pre-study inhaled corticosteroid dose of 1038 microg/day. Mean morning PEF increased by 37 L/min and 36 L/min with budesonide/formoterol and budesonide plus formoterol, respectively, versus an increase of 5 L/min with budesonide (P<0.001 for both vs. budesonide). Budesonide/formoterol increased time to first mild exacerbation (P<0.005) versus budesonide. Budesonide/formoterol and budesonide plus formoterol had similar efficacy. All treatments were well tolerated and the incidence of class-related adverse events was similarly low in all groups. Changes in serum potassium and plasma cortisol were comparable across treatments.\n High-dose budesonide/formoterol (320/9 microg, two inhalations bd) is effective and well tolerated in patients with persistent symptomatic asthma. The findings also support the safety of regular high-dose formoterol (36 microg/day).", "The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma, but tolerance may develop to its bronchoprotective effect. We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily, instead of the usual dose of 50 microg twice daily, in adolescents receiving regular glucocorticoid inhalations. Methods. In a randomized, double-blind, 2x28-day crossover study, we administered salmeterol (50 microg) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance. Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period. The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise.\n Fourteen subjects with a mean age of 13.1 years completed the study. The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours. After the 28th consecutive daily dose of salmeterol, the bronchoprotective effect was significantly greater than that of placebo at 1 hour, but not at 9 hours.\n We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours, but that this effect may wane during regular once-daily salmeterol treatment, despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids.", "The present study was set up to investigate whether salmeterol in children with asthma already treated with inhaled corticosteroids (ICS) leads to a sustained bronchodilator effect and decreased bronchial responsiveness, both during the day and night. Furthermore, we investigated whether cessation of salmeterol leads to a rebound increase in bronchial responsiveness. Forty children with asthma (aged 7-15 yrs) using ICS participated in a randomized, double-blind, parallel study. They received either twice daily 50 micrograms salmeterol or placebo. FEV1 and provocative concentration of methacholine that caused a 20% fall in FEV1 (PC20) were measured at 4:00 P.M. and 4:00 A.M. at baseline and after 16 wk. The same measurements were performed at 4:00 P.M. at 8 h after the first dose, and after 1 and 8 wk. After cessation of the study drug, FEV1 and PC20 were measured at 12 and 20 h and after 1 wk. Overall mean FEV1 from 1 to 16 wk of treatment was significantly higher in the salmeterol group than in the placebo group (difference, 4.9 +/- 2.0%, p = 0.01). Evolution in time of FEV1 did not differ significantly between the two groups (p = 0.09). Overall mean PC20 from 1 to 16 wk of treatment was not significantly higher with salmeterol than with placebo (difference, 0.7 +/- 0.4 doubling dose [DD] p = 0.07); evolution in time of PC20 did not differ significantly between the two groups (p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)", "We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients with mild-to-moderate asthma with asthma symptoms and related the effectiveness of these therapies between patients who used concurrent inhaled corticosteroids (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind, placebo-controlled crossover trial with 367 adult asthmatics randomized to each trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all patients throughout the trial. Only 80% of patients, albeit the majority, were receiving maintenance treatment with ICS throughout this trial; this reflects practice current in early 1990. Each study day, patients recorded their morning and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use of rescue medication. Both morning and evening PEF were greater during treatment with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3 L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm was also more effective than Sb or P in lowering diurnal variation in PEF and increasing the percentage of symptom-free days and rescue-free days and nights with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in increasing evening PEF and the percentage of symptom-free days (p < 0.05) and rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with Sb and P was observed in those patients using ICS (p < 0.001 for all treatment comparisons), and to a greater extent than in those patients not using ICS (i.e., Sm was more effective than Sb and P in just six of the 20 treatment comparisons; p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the management of mild-to-moderate asthma and it further improves asthma control in patients already using ICS.", "This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.\n Adult patients with mild persistent asthma (> or = 80% predicted FEV1) receiving 200-500 mug of BDP or equivalent were randomised to receive either FP 100 mug or SFC 50/100 mug twice daily from a Diskus inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.\n A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 - 0.89, p < 0.001) at week 2 and 0.81 (0.71 - 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV1 was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 - 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 - 0.34, p = 0.060).\n SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV1 values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry\n NCT00370591.", "In severe chronic asthma, long-term oral steroids may be necessary to control symptoms. In patients in whom such treatment was under consideration, the efficacy and safety of salmeterol xinafoate 100 micrograms b.i.d. was investigated in a randomized, double-blind, placebo-controlled parallel-group, multicentre study. One hundred and nineteen chronic symptomatic asthmatics were randomized to receive either salmeterol, 100 micrograms b.i.d. (n = 55; baseline % predicted morning peak expiratory flow (PEF) 59%; forced expiratory volume in one second (FEV1) 66%) or placebo (n = 64; baseline % predicted morning PEF 63%; FEV1 66%) both via the Diskhaler. Morning and evening PEF and asthma symptoms were recorded in daily record booklets by the patient over a 12 week period. A significant improvement in morning PEF was achieved after 1 month in the salmeterol treated group; this persisted throughout the treatment period (estimated treatment difference 22 L.min-1). There was a significant increase in the proportion of symptom-free nights experienced by the salmeterol treated group (33 (SD 32) %) compared with placebo (13 (26) %), and a significant decrease in daily use of relief medication (mean decrease 5.1 (4.7) doses per day with salmeterol, 2.5 (4.0) doses with placebo). Both treatments were well-tolerated, with no evidence of any difference in the side-effects associated with beta 2-agonists. In conclusion, the addition of salmeterol (100 micrograms daily) to the existing treatment of chronic asthmatics under consideration for maintenance oral corticosteroid therapy is well-tolerated, improves lung function and provides additional symptom control.", "Recent studies have raised concern that regular inhalation of beta2 -agonists may cause a worsening of asthma control compared with on-demand dosing regimens.\n The objective of this study was to compare the effect of twice daily formoterol (Foradil), 4 times daily albuterol, and on-demand albuterol on bronchial hyperresponsiveness (BHR), lung function measurements, symptoms, and other indicators of disease control over 6 months inpatients with asthma of moderate or greater severity receiving concomitant inhaled corticosteroids. We also looked for occurrence of rebound BHR on discontinuation of treatment.\n This was a multicenter, parallel-group, double-blind, clinical trial. Methacholine PC20 was the primary outcome variable. Other outcome variables included symptom scores, use of rescue medication, morning peak expiratory flow (PEF), serial FEV1 measurements, and asthma exacerbations.\n Of the 271 randomized patients, 217 completed the study. Formoterol was significantly superior to on-demand albuterol with regard to methacholine PC20, FEV1, PEF, symptom scores, and use of rescue medication at each measured time point/interval. Regular albuterol was superior to on-demand albuterol with regard to PC20 and FEV1, but not PEF or various clinical scores. After a small drop in the magnitude of bronchoprotection and bronchodilatation occurring shortly after randomization, there was no evidence of progressive tolerance to either regular treatment for any of the measured variables or of rebound increase in BHR 2 days after the end of treatment. The formoterol group had the lowest number of exacerbation days, as defined by high intake of rescue bronchodilator and/or symptom scores, whereas the number of exacerbations requiring increased corticosteroid coverage was similar in the 3 groups.\n In patients with asthma of moderate or greater severity receiving inhaled corticosteroids, formoterol taken twice daily resulted in superior bronchoprotection, bronchodilatation, and clinical control compared with on-demand albuterol over 6 months. Four times daily albuterol was superior to on-demand albuterol for only some of the end points. Progressive tolerance and a rebound increase in BHR on discontinuation of beta-agonists were not found", "Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms. However, they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being.\n We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality-of-Life Questionnaire, as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids.\n This was a randomized, double-blind, placebo-controlled, parallel-group study of 506 patients. Patients were treated with 42 microg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler.\n Mean change from baseline in asthma quality-of-life scores was significantly greater (p < or = 0.006) after 12 weeks of treatment with salmeterol compared with placebo (\"as-needed\" albuterol) in global scores (1.08 vs 0.61) and individual domains (activity limitations, 0.91 vs 0.54; asthma symptoms, 1.28 vs 0.71; emotional function, 1.17 vs 0.65; and environmental exposure, 0.84 vs 0.47). Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV1 (0.42 L vs 0.15 L, p < 0.001), morning peak expiratory flow (47 L/min vs 14 L/min, p < 0.001), evening peak expiratory flow (29 L/min vs 11 L/min, p < 0.001), and asthma symptom scores (daytime scores reduced by 0.55 vs 0.30, p < 0.001). Patients treated with salmeterol used significantly less supplemental albuterol (reduced by 3 puffs/day vs 1 puff/day, p < 0.001).\n Salmeterol provided significantly greater improvement in quality-of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids. These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy.", "The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist, formoterol, to low doses of an inhaled corticosteroid, budesonide, for 1 yr in subjects with mild asthma, receiving no or only a small dose of inhaled corticosteroid. The 698 corticosteroid free patients (Group A) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, or placebo. The 1,272 corticosteroid-treated patients (Group B) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, 200 microg budesonide, or 200 microg budesonide plus 4.5 microg formoterol. The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days. In Group A, budesonide alone reduced the risk for severe exacerbations by 60% and poorly controlled days by 48%; adding formoterol increased lung function with no change in other end points. By contrast, in Group B, adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30%, respectively. Thus, in corticosteroid-free patients, low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control, and in patients already receiving inhaled corticosteroid, adding formoterol was more effective than doubling the corticosteroid dose.", "Using BAL, we studied the effects of 8 wk of treatment with salmeterol on airway inflammation in nine asthmatic subjects in a double-blind crossover placebo-controlled protocol. The study patients were all receiving regular inhaled corticosteroid therapy (400 to 1,000 micrograms beclomethasone dipropionate per day) and inhaled albuterol for symptomatic relief, i.e., subjects who might be considered suitable for treatment with salmeterol. The asthmatic group had significant differences in numbers of epithelial cells and eosinophils in BAL compared with a group of 15 normal control subjects (p < 0.01). During salmeterol treatment mean morning and evening peak flow rates were increased (p < 0.05). There was no significant change in BAL cell profile and no change in percentages of CD4 and CD8 lymphocytes or proportion of lymphocytes expressing HLA-DR after salmeterol. In conclusion, we were unable to demonstrate any significant anti-inflammatory effect of regular salmeterol therapy on airway inflammation using BAL in these asthmatic patients. At the same time, there was equally no evidence of a deterioration in the underlying inflammatory disease process.", "This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone.\n Copyright 2004 Wiley-Liss, Inc.", "Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long-acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma.", "Twenty-four children aged 12-17 years entered a randomized, double-blind placebo-controlled study investigating the use of salmeterol in chronic severe asthma. In addition to their usual medication, the children were given either placebo or 100 micrograms salmeterol b.d. by dry powder inhalation. Treatment was continued throughout one term at a residential school for asthma. Symptom scores, peak expiratory flow rates, spirometry and quality-of-life scores were compared between the two treatment groups. One child withdrew during the run-in period. Twelve pupils received placebo and 11 pupils received salmeterol. There were consistent improvements in favour of salmeterol, reaching statistical significance for morning and evening peak flow rates and spirometry when measured on four occasions during the study period. There were no medication-related adverse events recorded and no pulse rate changes. Salmeterol (100 micrograms b.d.) is well tolerated and efficacious in older children with chronic severe asthma.", "This long-term prospective study was conducted in African Americans with persistent asthma to examine the safety and effectiveness of the combination of the inhaled corticosteroid, fluticasone propionate (FP), and the long-acting beta-agonist, salmeterol, compared with FP alone.\n This was a randomized, double-blind, parallel group, multi-center trial in adolescent and adult subjects >/=12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period (FP/salmeterol [FSC] 100/50 mcg [n=239] or FP 100 mcg [n=236] BID), and a 4-week FP 250 mcg BID run-out period. Annualized exacerbation rate was the primary outcome for comparing the two treatments. Other measures of asthma control included peak expiratory flow, asthma symptoms, and albuterol use. Safety was assessed through adverse events.\n Exacerbation rates were not significantly different in those treated with FSC 100/50 mcg (0.449 per year) compared with FP 100 mcg (0.529 per year, p=0.169). When the per-protocol analysis was applied, the rates were 0.465 and 0.769 per year for FSC 100/50 mcg and FP 100 mcg, respectively. Treatment with FSC 100/50 mcg provided statistically greater improvements in lung function measures and nighttime awakenings (p</=0.050) and demonstrated numerically lower daily symptoms (p=0.216) and albuterol use (p=0.122). Two subjects treated with FSC 100/50 mcg were hospitalized for an asthma exacerbation compared to three treated with FP 100 mcg. The overall incidence of adverse effects during double-blind treatment was similar between the FSC 100/50 mcg and FP 100 mcg treatment groups (61% and 68%, respectively). Frequent study visits were required of subjects during this long-term study, and it remains unknown whether this intervention may affect generalizability.\n In this large, prospective study among African Americans with asthma, the addition of salmeterol to FP resulted in a similar low rate of exacerbations and improved other markers of asthma control. Both FSC 100/50 mcg and FP 100 mcg were well-tolerated, and the overall safety-profiles were similar over 1 year of treatment.", "Many patients with persistent asthma need both long-acting bronchodilators and inhaled corticosteroids for optimal asthma control.\n Our purpose was to compare the efficacy and safety of salmeterol 50 microg combined with fluticasone 100 microg (in a combination dry powder product) with that of placebo, fluticasone, or salmeterol alone.\n A 12-week randomized, double-blind, multicenter study was conducted in 356 patients aged 12 years or older with asthma. After a 14-day screening period, patients were randomized to treatment with salmeterol 50 microg combined with fluticasone 100 microg (combination product), salmeterol 50 microg, fluticasone 100 microg, or placebo administered in the Diskus dry powder inhaler (GlaxoWellcome, UK) twice daily.\n Mean change in FEV(1) at end point was significantly (P < or =.003) greater with the combination product (0.51 L) compared with placebo (0.01 L), salmeterol (0.11 L), and fluticasone (0.28 L). The combination product significantly increased (P < or =.013) area under the curve compared with placebo and fluticasone on day 1 and compared with placebo, salmeterol, and fluticasone at week 1 and week 12. Patients in the combination product group were less likely to withdraw from the study because of worsening asthma compared with those in the other groups (P < or =.020). The combination product significantly increased (P < or =.012) morning PEF (combination, 52.5 L/min; placebo, -23.7 L/min; salmeterol, -1.7 L/min; fluticasone, 17.3 L/min) and evening PEF at end point compared with the other groups. The combination product significantly (P < or =.025) reduced symptom scores and albuterol use compared with the other treatments and increased the percentage of nights with no awakenings and the percentage of days with no symptoms compared with placebo and salmeterol. All treatments were equally well tolerated.\n Salmeterol 50 microg and fluticasone 100 microg combined in the Diskus powder delivery device offers significant clinical advantages over salmeterol or fluticasone alone at the same doses.", "Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma.\n After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period.\n Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001).\n The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.", "Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.", "For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid (ICS) therapy, the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose.\n To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma.\n A randomized, multicenter, double-blind, active-controlled, parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy. Patients received fluticasone propionate-salmeterol (100/50 microg) or fluticasone propionate (100 microg) alone twice daily for 12 weeks.\n The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone. The overall incidence of adverse events was 59% for fluticasone propionate-salmeterol and 57% for fluticasone propionate. Both treatments were well tolerated. Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma. Changes in heart rate, blood pressure, and laboratory variables were infrequent and were similar between treatments. No patients had clinically significant abnormal electrocardiographic findings during treatment. Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the fluticasone propionate-salmeterol group and 5% in the fluticasone propionate group.\n In pediatric patients with persistent asthma, fluticasone propionate-salmeterol twice daily was well tolerated, with a safety profile similar to that of fluticasone propionate used alone.", "There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.", "The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.\n Copyright 2002 Wiley-Liss, Inc.", "Pulmonary function tests (PFTs) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability. The aim of our study was to determine the effects of anti-asthma treatment in children, equally on FEV(1), FEF25-75%, R(int) and SR(aw) values.\n Children 6-18 years of age with moderate atopic asthma were randomized to 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive 200 microg budesonide (B) (n=29), 5 or 10 mg (according to age) montelukast (M) (n=29), 200 microg B + 5 or 10 mg M (n=29), 200 microg B + 9 microg formoterol (F) (n=29) or placebo (n=27). FEV(1,) FEF25-75%, R(int), SR(aw) were measured before and after treatment.\n R(int), SR(aw), FEV(1) improved significantly in all active treatment groups while FEF25-75% improved significantly only in BM group and M group. Combination therapy, showed significantly greater effects on R(int) than monotherapy: BM group compared to B group (P=0.01) and M group (P=0.03) and BF group compared to B group (P=0.01) and M group (P=0.04).\n This study shows that using single parameter for monitoring asthma can be misleading. Using combination of lung function techniques provides better assessment of treatment. Results of our study confirm this hypothesis. The best effect on large and small airways was achieved with combined anti-inflammatory therapy.", "This multicentre double-blind, double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg (Seretide, GlaxoWellcome, France) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone. Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in, and had received treatment with beclomethasone dipropionate or budesonide 1500-2000 microg day(-1) or fluticasone propionate 750-1000 microg day(-1) for at least 4 weeks prior to run-in. In total, 503 patients receiving inhaled corticosteroids were randomized to 28 weeks' treatment with either salmeterol/fluticasone propionate (50/500 microg) via a single Diskus inhaler (combination) and placebo, or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers (concurrent), or fluticasone propionate 500 microg and placebo. All treatments were administered twice daily, mean morning peak expiratory flow rate (PEFR) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study. Over weeks 1 to 12, improvement in adjusted mean morning PEFR was 35 and 33 l min(-1), respectively, in the combination and concurrent therapy treatment groups (12 and 10% increase from baseline, respectively). The mean difference between treatments was -3 l min(-1) (90% confidence interval -10.4 l min(-1)) which was within the criteria for clinical equivalence. However, the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR (P<0.001) and other measures of lung function, whilst clinical equivalence of the combination and concurrent therapies was observed. All three treatments were well tolerated. In addition, there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations, which, for each treatment group, were no significantly different from baseline at the end of the treatment period. Thus, the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs, and both combination and concurrent therapy are superior to administration of the same dose of corticosteroid alone.", "Current UK and international guidelines on asthma management recommend that, in pediatric patients still symptomatic on treatment with high-dose inhaled corticosteroids, consideration should be given to the introduction of regular twice daily long-acting beta 2-agonists.\n The purpose of this study was to assess the efficacy and safety of inhaled salmeterol xinafoate 50 micrograms bid via the Diskhaler when added to the existing treatment of children with moderate to severe asthma.\n A 12-week multicenter, double-blind, placebo-controlled, parallel group study was conducted at 78 hospital centers throughout the United Kingdom, involving 210 asthmatic children aged between 4 and 16 years of age. Morning peak expiratory flow (PEF), evening PEF, night-time and daytime symptoms and relief medication usage were recorded daily by the patient or parent over a 12-week treatment period.\n Compared with placebo, the addition of salmeterol xinafoate to existing high dose inhaled corticosteroid treatment significantly improved mean morning PEF expressed as percent predicted (PEF-PP) during the first 4 weeks of treatment (median increase 6.5 percentage points P < .001). This effect persisted throughout the 12-week treatment period (P < .05). Both groups demonstrated an overall improvement in mean morning PEF-PP, 7.5 percentage points for salmeterol xinafoate and 4 percentage points for placebo. The mean evening PEF-PP followed a similar although less pronounced trend which was significant only during the first 4 weeks of treatment (P = .014). Daytime relief medication and recorded symptoms were reduced significantly in both groups. There was a greater improvement in the number of symptom-free days during the first 4 weeks (P < .01) and the last 4 weeks (P < .05) of treatment for salmeterol xinafoate. The overall incidence and nature of minor adverse events was similar in both groups.\n This study demonstrates that the addition of salmeterol xinafoate to inhaled corticosteroid therapy in symptomatic asthmatic children significantly improves morning PEF-PP, and reduces their symptoms and use of relief medication.", "Inhaled corticosteroids (ICSs) are the preferred maintenance therapy for adults and children with mild, moderate and severe persistent asthma, with the addition of a long-acting beta(2)-adrenoceptor agonist to ICS therapy recommended for patients with moderate or severe persistent asthma. The efficacy and safety of the combination of budesonide and formoterol delivered via dry powder inhaler (DPI) is well documented.\n To compare the efficacy and safety of budesonide/formoterol pressurised metered-dose inhaler (budesonide/formoterol pMDI; Symbicort pMDI, AstraZeneca LP, Wilmington, DE, USA) with budesonide pMDI (Pulmicort pMDI, Astra [corrected] Zeneca, Lund, Sweden), formoterol DPI (Oxis Turbuhaler, AstraZeneca, Lund, Sweden), budesonide plus formoterol in separate inhalers (budesonide pMDI + formoterol DPI) and placebo.\n This was a 12-week randomised, double-blind, double-dummy, placebo-controlled study.\n This multicentre study was conducted in the respiratory specialty clinical practice setting.\n The study included 596 patients > or =12 years of age with moderate to severe persistent asthma previously receiving ICSs.\n After 2 weeks on budesonide pMDI 80 microg x two inhalations (160 microg) twice daily, patients received budesonide/formoterol pMDI 160 microg/4.5 microg x two inhalations (320 microg/9 microg); budesonide pMDI 160 microg x two inhalations (320 microg) + formoterol DPI 4.5 microg x two inhalations (9 microg); budesonide pMDI 160 microg x two inhalations (320 microg); formoterol DPI 4.5 microg x two inhalations (9 microg); or placebo twice daily.\n There were two prespecified primary efficacy variables: mean change from baseline in morning predose forced expiratory volume in 1 second (FEV(1)), obtained approximately 12 hours after the most recent administration of study medication at home and immediately before the next administration of study medication at the clinic; and mean change from baseline in 12-hour FEV(1), assessed as the average change in FEV(1) from serial spirometry over the 12-hour period after administration of the morning dose of study medication at the clinic.\n Mean changes from baseline in morning predose FEV(1) at end of treatment were greater (p < or = 0.049) with budesonide/formoterol pMDI (0.19L) versus budesonide pMDI (0.10L), formoterol DPI (-0.12L) and placebo (-0.17L). Mean changes from baseline in 12-hour FEV(1) were greater (p < or = 0.001) with budesonide/formoterol pMDI after 1 day (0.37L), 2 weeks (0.34L) and at end of treatment (0.37L) versus budesonide pMDI (0.11, 0.15 and 0.15L) and placebo (0.09, -0.03 and -0.03L), and after 2 weeks and at end of treatment versus formoterol DPI (0.19 and 0.17L). Fewer (p < or = 0.025) patients receiving budesonide/formoterol pMDI versus monoproducts or placebo met worsening asthma criteria. Results were similar in the budesonide/formoterol pMDI group and the budesonide pMDI + formoterol DPI group on all measures. All treatments were well tolerated with similar safety profiles.\n In this population, twice-daily budesonide/formoterol pMDI provides asthma control significantly greater than the monocomponents or placebo and comparable with budesonide pMDI + formoterol DPI. Safety profiles were similar for all treatments.", "Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.", "Previous studies have indicated the benefits of adding long acting beta(2) agonists to inhaled corticosteroids in the maintenance treatment of moderate to severe asthma. The effects of adding eformoterol to corticosteroids on asthma control and exacerbations in patients with mild to moderate asthma were studied.\n After a run in period of 7-14 days on existing medication, 663 symptomatic patients were randomised to receive budesonide Turbohaler 400 microg twice daily together with either eformoterol Turbohaler 9 micro g (delivered dose) or placebo twice daily. After 4 weeks patients whose asthma was well controlled (n=505) were re-randomised to receive budesonide 400 microg daily and either eformoterol 9 micro g or placebo twice daily for a further 6 months.\n Patients receiving eformoterol achieved asthma control 10 days sooner than those receiving budesonide alone, and improvements in lung function, symptoms, quality of life, and relief beta(2) agonist use were significantly greater with eformoterol. During the 6 month follow up the frequency of mild exacerbations was significantly lower in the eformoterol group than in those receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled asthma was 97 days in the eformoterol group compared with 42 days in the placebo group (p=0.003).\n Adding eformoterol to a low or moderate dose of budesonide in mild asthma resulted in faster and more effective control than treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to be reduced while also decreasing the rate of mild exacerbations compared with budesonide alone. These data suggest a therapeutic advantage of adding eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.", "The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma.\n In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout.\n One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively).\n Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.", "The effect of adding inhaled salmeterol to inhaled corticosteroids was studied in patients with poorly controlled nocturnal asthma. In a double-blind, cross-over study, 20 patients were randomized to receive either salmeterol 50 micrograms twice daily or placebo via a Diskhaler after a 1-week run-in period. After 4 weeks of treatment, patients were subsequently crossed over to receive the other treatment for a further 4 weeks with a 2-week wash-out period in between. The response to treatment was assessed by peak expiratory flow rates (PEF) measured in the morning and evening, symptom scores of asthma, number of bronchodilators used, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at regular intervals. Patients' preference for the Diskhaler or metered-dose inhaler was assessed at the last visit. The results showed that morning PEF was significantly higher while on salmeterol than on placebo (296.9 +/- 70.2 vs 274.6 +/- 77.4 L/min). Evening PEF showed a trend towards a higher value while on salmeterol than on placebo (321.1 +/- 73.4 vs 288.7 +/- 79.4 L/min), but the difference was not significant. There was no statistically significant improvement in symptom scores, number of rescue bronchodilators used and FEV1 or FVC between the two treatment groups. The occurrence of side effects in terms of tremors and palpitations between treatment and placebo were similar. There were more patients who preferred Diskhaler to metered-dose inhaler (70% vs 30%). We conclude that salmeterol 50 micrograms twice daily produces significant improvement in morning PEF and is well tolerated in patients with nocturnal asthma. Diskhaler is a device which is easy to use and preferred to a metered-dose inhaler.", "To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids.\n A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 microg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV1), lung volumes, and airway conductance.\n Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen.\n These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids.", "This study compared the efficacy and tolerability of the combination of fluticasone propionate (FP) and salmeterol (SAL) delivered via a single hydrofluoroalkane (HFA) 134a metered-dose inhaler (MDI) with those of its 2 components alone delivered via a chlorofluorocarbon (CFC) MDI and placebo (PLA) delivered via HFA MDI in adolescent and adult patients with persistent asthma that was not controlled by medium doses (equivalent to FP 440-660 microg/d) of inhaled corticosteroids (ICSs).\n This was a randomized, double-blind,placebo-controlled, parallel-group study consisting of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period. Participants had to be > or =12 years of age and have a diagnosis of asthma requiring pharmacotherapy for at least 6 months before the study. Patients had to have used ICS therapy for > or =3 months before the study and at a consistent dose for the previous month. Lack of asthma control was defined as a forced expiratory volume in 1 second (FEV(1)) that was 40% to 85% of the predicted value. Patients could not enter the double-blind treatment period if they had 3 days when they required >12 puffs of rescue albuterol per day or >3 nighttime awakenings due to asthma that required treatment with albuterol during the 7 days before the randomization visit. Patients were randomized to receive one of the following treatments delivered via MDI twice daily for 12 weeks: FSC 220/42 microg HFA (2 inhalations of FSC 110/21 microg; 125 microg/21 microg ex-valve); FP 220 microg CFC (2 inhalations of FP 110 microg); SAL 42 microg CFC (2 inhalations of 21 microg); or 2 inhalations of PLA HFA. The primary efficacy end point for FSC versus FP was the mean area under the 12-hour serial FEV(1) curve relative to the prerandomization baseline (FEV(1) AUC(bl)). The primary efficacy end points for FSC versus SAL were the mean change from baseline in morning predose FEV(1) at end point and the probability of not being withdrawn from the study due to worsening asthma. Tolerability assessments included electrocardiograms, routine clinical laboratory tests, vital signs, oropharyngeal examinations, and physical examinations. Adverse events were assessed at each clinic visit.\n Thirty-two adolescent and 333 adult patients were randomly assigned to receive double-blind treatment. The treatment groups were comparable at baseline with respect to demographic characteristics (mean age, 38-41 years; white race, 78%-88%) and pulmonary function (mean percent predicted FEV(1), 68%-69%; mean asthma symptom score, 1.6 [scale 0-5]; and mean daily albuterol use, 3.1 puffs). After 12 weeks of treatment, the mean FEV(1) AUC(bl) was significantly greater in patients who received FSC compared with those who received FP, SAL, or PLA (7.0, 3.6, 5.3, and 1.4 L-h, respectively; all comparisons, P < or = 0.020). At end point, the mean change from baseline in morning predose FEV(1) for FSC was significantly greater than that for FP, SAL, and PLA (0.41, 0.19, 0.15, and -0.12 L; all comparisons, P < or = 0.001). During 12 weeks of treatment, 7% of patients receiving FSC were withdrawn due to worsening asthma, compared with 24% of patients receiving SAL and 54% of patients receiving PLA (P < 0.001); 11% of patients receiving FP were withdrawn due to worsening asthma. Treatment with FSC resulted in significant improvements in morning and evening peak expiratory flow compared with FP, SAL, and PLA (both, P < 0.001); need for rescue albuterol compared with FP and PLA (P < or =0.005); and asthma symptom scores compared with PLA (P < 0.001). The tolerability of FSC was similar to that of FP or SAL alone. The incidence of possibly drug-related adverse events was generally similar across treatment groups, and the most common (occurring in > or= 2% of patients) were headache (1%-4%), throat irritation (1%-2%), candidiasis of the mouth/throat (0%-2%), unspecified oropharyngeal plaques (0%-2%), and palpitations (0%-2%).\n In these adolescent and adult patients whose asthma was not controlled by medium doses of an ICS, FSC delivered via HFA 134a MDI (2 inhalations of 110/21-microg strength administered BID) was more effective in improving lung function than FP or SAL monotherapy or PLA. All treatments were well tolerated.", "Exercise is a common trigger of asthma symptoms in patients with persistent asthma.\n To evaluate the protective effect of fluticasone/salmeterol against exercise-induced bronchospasm.\n Multicenter, randomized, double-blind, parallel-group trial of 192 asthma patients who used moderate-dose inhaled corticosteroids. Patients (aged 12-50 years; mean forced expiratory volume in 1 second [FEV1], 78% of predicted at baseline) were randomized to receive fluticasone/salmeterol (250/50 microg twice daily) or fluticasone alone (250 microg twice daily) via Diskus for 4 weeks. Exercise challenge tests were performed 1 and 8.5 hours after administration of the first (day 1) and last (week 4) doses of blinded study medication.\n On day 1 and at week 4, mean +/- SEM values for the maximal percentage decline in FEV1 1 hour after drug administration were 11.4% +/- 1.5% and 10.9% +/- 1.5% for fluticasone/salmeterol compared with 20.0% +/- 1.7% and 18.4% +/- 1.8% for fluticasone (P < .001). At 8.5 hours, mean +/- SEM values on day 1 and at week 4 were 11.6% +/- 1.4% and 8.9% +/1.1%, respectively, for fluticasone/salmeterol and 12.6% +/- 1.6% and 12.9% +/- 1.4%, respectively, for fluticasone (P = .01 at week 4). More fluticasone-treated patients did not complete the 8.5-hour exercise challenges (36% on day 1 and 33% at week 4) compared with the fluticasone/salmeterol group (18% each) (P < or = .01). Improvements in peak expiratory flow rate and albuterol rescue-free days were significantly greater with fluticasone/salmeterol vs fluticasone over weeks 1 to 4 (P < or = .03).\n Consistent with the improvements in other measures of asthma control, long-term fluticasone/salmeterol therapy also provided protection against exercise-induced bronchospasm in patients with persistent asthma.", "We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. Conclusion: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.", "Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.", "The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.\n After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.\n The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.\n In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma." ]

[ "17995496", "10899490", "9746385", "16875644", "15663589", "12387462", "10802404", "10989245", "12197367", "18703472", "11991445", "17634547", "11600531", "19193505", "15214586", "11770188", "9255748", "9699198", "7616869", "12034516", "9932566", "17085380", "19167925", "16894336", "19731119", "8861087", "17006377", "11809341", "19177255", "16143225", "9032742" ]

[ "Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.", "Effects of tibolone and continuous combined hormone replacement therapy on parameters in the clotting cascade: a multicenter, double-blind, randomized study.", "A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms.", "Effects of tibolone and continuous combined conjugated equine estrogen/medroxyprogesterone acetate on the endometrium and vaginal bleeding: results of the OPAL study.", "The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial.", "Dose-response analysis of effects of tibolone on climacteric symptoms.", "Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women.", "The comparison of effects of tibolone and conjugated estrogen-medroxyprogesterone acetate therapy on sexual performance in postmenopausal women.", "Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women.", "The effects of tibolone in older postmenopausal women.", "Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol and norethindrone acetate in preventing postmenopausal bone loss.", "Effect of tibolone on breast cancer cell proliferation in postmenopausal ER+ patients: results from STEM trial.", "Prevention of bone loss with tibolone in postmenopausal women: results of two randomized, double-blind, placebo-controlled, dose-finding studies.", "Tibolone in postmenopausal women with systemic lupus erythematosus: a pilot study.", "Efficacy and safety of oral tibolone 1.25 or 2.5 mg/day vs. placebo in postmenopausal women.", "Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy.", "Comparison of transvaginal ultrasonography and endometrial biopsy in endometrial surveillance in postmenopausal HRT users.", "Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT.", "A comparative study of two hormone replacement therapy regimens on safety and efficacy variables.", "Prospective, randomised study with three HRT regimens in postmenopausal women with an intact uterus.", "Continuous combined hormone replacement therapy compared with tibolone.", "Effect of different preparations of hormone therapy on sexual dysfunction in naturally postmenopausal women.", "Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.", "Different effects of tibolone and low-dose EPT in the management of postmenopausal women with primary headaches.", "Comparative effects of conventional hormone replacement therapy and tibolone on climacteric symptoms and sexual dysfunction in postmenopausal women.", "Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints.", "Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo-controlled study.", "The influence of tibolone on quality of life in postmenopausal women.", "Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA treatment in postmenopausal women with female sexual dysfunction.", "Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women.", "Effect on sexual life--a comparison between tibolone and a continuous estradiol-norethisterone acetate regimen." ]

[ "The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy.\n A randomised, double-blind, double-dummy, group comparative intervention trial.\n Multicentre study executed in 32 centres in 7 European countries.\n Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years.\n Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks.\n Prevalence of vaginal bleeding, hot flushes and adverse events.\n The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001).\n Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.", "To determine the effects of tibolone and continuous combined HRT (ccHRT) on parameters in the clotting cascade.\n Randomized, double-blind study.\n Hemostasis unit of a university hospital clinic in Germany.\n Sixty healthy postmenopausal women.\n Twenty-nine subjects were treated with tibolone (2.5 mg/d) and 31 with oral ccHRT containing estradiol (2 mg/d) + estriol (1 mg/d) + norethindrone acetate (1 mg/d).\n Effects on parameters in the clotting cascade at baseline and after 12 and 24 weeks of treatment.\n Tibolone increased fibrinolysis parameters without significantly altering coagulation parameters. Treatment with ccHRT resulted in a stimulating effect on parameters of both fibrinolysis and coagulation. Tibolone showed a stronger reduction of factor VII activity; less reduction of AT-III, protein C activity, and protein S activity; stronger increase of the activated partial thromboplastin time, plasminogen and plasminogen-antiplasminogen complexes; and less increase of D-Dimer than ccHRT. Both preparations similarly reduced climacteric complaints, whereas tibolone showed less breast complaints than ccHRT.\n This study confirms that tibolone, and to a lesser extent also ccHRT, changes hemostasis parameters toward a more fibrinolytic profile, which may diminish the risk of venous thrombosis.", "To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability.\n Double-blind, randomised controlled trial.\n Twenty-nine sites in Denmark, nine in Norway and six in Sweden.\n Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy.\n Daily treatment with tibolone 2.5 mg (n = 218) or 17beta-oestradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA) (n = 219).\n Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12, 24 and 48 weeks.\n Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E2/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E2/NETA (P < 0.0001), mainly during the first six treatment cycles.\n Both tibolone and E2/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding.", "The primary objective of the Osteoporosis Prevention and Arterial effects of tiboLone study was to compare the effect of tibolone and placebo on the progression of the common carotid artery intima-medial thickness; the common carotid artery intima-medial thickness and bone data will be presented elsewhere. A secondary objective was to assess the effects of tibolone (2.5 mg), continuous combined conjugated equine estrogen/medroxyprogesterone acetate [0.625/2.5 mg], and placebo on the endometrium and vaginal bleeding; these results are the subject of this report.\n This 3-year, three-arm, international, randomized, double-blind, parallel group, placebo-controlled clinical trial enrolled 866 postmenopausal women (aged 45-79 years). The endometrium was assessed by annual transvaginal ultrasound scans and end-of-study biopsies (United States/United Kingdom centers only). Vaginal bleeding was recorded in daily diaries.\n Endometrial thickness measured by transvaginal ultrasound scan increased slightly during the first year with tibolone and conjugated equine estrogen/medroxyprogesterone acetate, without any further progression. After 3 years, there were no significant differences between the tibolone, conjugated equine estrogen/medroxyprogesterone acetate, and placebo groups in the incidence of proliferation (1.4%, 4.8%, and 0%, respectively), endometrial hyperplasia (0% in all groups), or cancer (1, 0, and 1 case, respectively). During the first 3 months, bleeding/spotting rates were greater with conjugated equine estrogen/medroxyprogesterone acetate (48%) than with tibolone (18%; P < .001) or placebo (3%; P < .001). During 3 years of treatment, the incidence of bleeding/spotting was 66%, 48%, and 23% for conjugated equine estrogen/medroxyprogesterone acetate, tibolone, and placebo, respectively. The mean number of bleeding/spotting days was greater in the conjugated equine estrogen/medroxyprogesterone acetate than the tibolone or placebo groups (61, 28, and 7 days, respectively; P = .023 vs tibolone; P < .0001 vs placebo). The mean number of bleeding/spotting episodes was also greater in the conjugated equine estrogen/medroxyprogesterone acetate group (13 episodes) compared with the tibolone group (six episodes; P < .001) and placebo group (four episodes; P < .001). Vaginal bleeding was more commonly reported as an adverse event with conjugated equine estrogen/medroxyprogesterone acetate than tibolone (26.4% vs 10.8%, P < .0001) and as the reason for premature discontinuation (9% vs 2%, P = .001).\n Compared with conjugated equine estrogen/medroxyprogesterone acetate, tibolone has a better tolerability profile with respect to vaginal bleeding but with a similar endometrial safety. These results reinforce the endometrial safety profile of tibolone.", "To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer.\n Double-blind, randomised, placebo-controlled, multicentre pilot study.\n Hospital outpatient clinic.\n Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer.\n Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months.\n Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins.\n Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months.\n Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.", "To assess the clinically optimal tibolone dose for the relief of climacteric complaints.\n A randomised, double blind, placebo-controlled trial.\n Twenty-eight centres in Norway, The Netherlands, Sweden and Finland.\n Seven hundred and seventy-five healthy postmenopausal women were randomised to tibolone in a daily dose of 0.625, 1.25, 2.5 or 5.0 mg or placebo for 12 weeks.\n At baseline, and after 4, 8 and 12 weeks, hot flushes, sweating, vaginal bleeding and adverse experiences were recorded.\n Change in frequency and intensity of hot flushes and sweating over 12 weeks.\n From week four onwards, 2.5 and 5.0 mg tibolone were significantly more effective than placebo, regarding the frequency of hot flushes and sweating (P < 0.001), whereas the 0.625 mg dose was not significantly different from placebo during the study. The frequency of hot flushes with the 1.25 mg dose was statistically significantly different from placebo, only from week eight onwards. The incidence of dropouts due to insufficient therapeutic effect was much higher in the tibolone 1.25 mg group (9.5%) than in the 2.5 (1.9%) and 5.0 mg (1.3%) groups. A dose-related increase in incidence of vaginal bleeding or spotting was observed (P < 0.0001). Bleeding incidence in the 5.0 mg dose group was about twice as high as in the 2.5 mg dose group. There was no difference in incidence of adverse experiences between the 2.5- and the 1.25 mg dose group.\n A daily dose of 2.5 mg tibolone is the clinically optimal dose for the treatment of climacteric complaints in postmenopausal women.", "To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial(R)).\n A 2-year randomised placebo-controlled study of 94 healthy women, 1-3 years after spontaneous menopause, receiving either placebo (n=23), 1.25 mg/day (n=36) or 2.5 mg/day (n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage.\n Fifty-one percent (n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% (n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% (n=5) in the placebo group. The women who bled in the placebo group were younger (P<0.01), had menopause at an earlier age (P<0.05), had a shorter duration since menopause (P<0.05) and had a higher median E2 serum level prior to bleeding (P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation.\n In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2-2.5 times more likely to present with vaginal bleeding compared with placebo (P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.", "To compare the effects of two different postmenopausal regimens on sexual performance.\n A single blind prospective clinical study was planned on fifty natural postmenopausal women with no absolute contraindication for hormone replacement therapy (HRT). A total of 25 women were randomized for tibolone therapy (group T) and the rest 25 for continuous conjugated estrogen (CE) 0. 625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg (group E) for a year. Two women in group T and four women in group E were excluded from the study as they didn't attend the control visit. At baseline and after a year, sexual performance parameters (sexual desire, coital frequency, orgasm frequency, vaginal dryness/dyspareunia) and after therapy subjective well-being, vasomotor symptoms, and side effects were assessed by score method designed by us.\n Treatment with either preparation significantly improved subjective well-being, vasomotor symptoms and vaginal dryness. The rates of overall side effects between two groups were not found statistically different (P=0.84). Tibolone therapy increased sexual desire and coital frequency (P=0.001, P=0.014).\n Both tibolone and continuous combined CE/MPA effectively improve the findings of hypoestrogenism and subjective well being. Moreover, tibolone effectively increases sexual performance. It is seen that tibolone with acceptable androgenic side effects can be an appropriate selection for HRT in postmenopausal women with decreased sexual desire.", "To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability.\n A double-blind, randomised comparative trial.\n Thirty-seven centres in six European countries.\n Five hundred and one postmenopausal women, under 65 years of age with an intact uterus.\n For 12 months, women received daily treatment with tibolone 2.5 mg (n = 250), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE-MPA, n = 251).\n The primary outcome was vaginal bleeding rate during cycles 4-6. The secondary outcomes were vaginal bleeding rate during cycles 1-3, 7-9 and 10-13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability.\n Treatment with tibolone led to a significantly lower bleeding rate during cycles 4-6 compared with CEE-MPA (15.0% vs 26.9%; P = 0.004); there was a similar difference during cycles 1-3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE-MPA at 12 months (P = 0.017). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE-MPA (2.4% vs 17.1%; P < 0.001).\n The vaginal bleeding rate during cycles 4-6 was significantly lower in women using tibolone. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone.", "Tibolone has estrogenic, progestogenic, and androgenic effects. Although tibolone prevents bone loss, its effects on fractures, breast cancer, and cardiovascular disease are uncertain.\n In this randomized study, we assigned 4538 women, who were between the ages of 60 and 85 years and had a bone mineral density T score of -2.5 or less at the hip or spine or a T score of -2.0 or less and radiologic evidence of a vertebral fracture, to receive once-daily tibolone (at a dose of 1.25 mg) or placebo. Annual spine radiographs were used to assess for vertebral fracture. Rates of cardiovascular events and breast cancer were adjudicated by expert panels.\n During a median of 34 months of treatment, the tibolone group, as compared with the placebo group, had a decreased risk of vertebral fracture, with 70 cases versus 126 cases per 1000 person-years (relative hazard, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001), and a decreased risk of nonvertebral fracture, with 122 cases versus 166 cases per 1000 person-years (relative hazard, 0.74; 95% CI, 0.58 to 0.93; P=0.01). The tibolone group also had a decreased risk of invasive breast cancer (relative hazard, 0.32; 95% CI, 0.13 to 0.80; P=0.02) and colon cancer (relative hazard, 0.31; 95% CI, 0.10 to 0.96; P=0.04). However, the tibolone group had an increased risk of stroke (relative hazard, 2.19; 95% CI, 1.14 to 4.23; P=0.02), for which the study was stopped in February 2006 at the recommendation of the data and safety monitoring board. There were no significant differences in the risk of either coronary heart disease or venous thromboembolism between the two groups.\n Tibolone reduced the risk of fracture and breast cancer and possibly colon cancer but increased the risk of stroke in older women with osteoporosis. (ClinicalTrials.gov number, NCT00519857.)\n 2008 Massachusetts Medical Society", "In this 2-year, randomized study, we compared the efficacy and tolerability of tibolone 2.5 mg (n = 75), tibolone 1.25 mg (n = 76) and estradiol 2 mg plus norethindrone acetate 1 mg (E2/NETA: n = 74) for preventing bone loss in postmenopausal women. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed every 6 months. Side-effects were assessed quarterly. After 24 months, the mean increase (+/- SD) in lumbar spine BMD from baseline was 3.6% +/- 2.9%, 1.9% +/- 3.5% and 6.8% +/- 4.5% in the tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA groups, respectively. All pairwise differences were significant. The proportion of responders (women with a change from baseline in lumbar spine BMD of > or = -2% after 2 years) was 95.7%, 89.0% and 98.5% with tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA, respectively. Similar results were obtained for femoral BMD, although the difference between tibolone 2.5 mg and E2/NETA was not significant at 24 months. Decreases in bone remodeling markers were similar in the three groups. Vaginal bleeding was more common in the E2/ NETA group (33.8%) than with tibolone 2.5 mg (12.0%) or tibolone 1.25 mg (9.2%), as was breast pain (23.0%, 2.7% and 2.6%, respectively). Each treatment effectively prevented bone loss. Overall, tolerability of tibolone was better than with E2/NETA, because of less frequent vaginal bleeding and breast pain. This may promote long-term adherence.", "Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue).\n Postmenopausal women with initially stage I/II, estrogen receptor-positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen.\n Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0% in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P=0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P=0.031). The incidence of adverse effects was comparable.\n In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation.", "Tibolone, a novel compound with tissue-specific effects, has been found to have antiresorptive properties in bone. To confirm the efficacy of tibolone and determine its minimum effective dose for prevention of bone loss in early postmenopausal women, two randomized, double-blind, placebo-controlled, dose-finding studies were performed. Seven hundred seventy healthy women postmenopausal within 1-4 yr, with normal bone density for their age, were treated for 2 yr with 0.3, 0.625, 1.25, or 2.5 mg tibolone daily or placebo. All subjects took supplemental calcium carbonate (500 mg daily). Bone mineral density (BMD) of the lumbar spine and right proximal femur was measured by dual-energy x-ray absorptiometry for up to 2 yr. At each dose level, except the lowest (0.3 mg), tibolone produced a progressive increase in lumbar spine and total hip BMD over the 2-yr treatment period; at 0.3 mg, total hip density was maintained. However, only the doses 1.25 mg and 2.5 mg produced a progressive increase in femoral neck BMD. The differences in mean percent change from baseline in spine and total hip density were significant (P < 0.05) for all tibolone dose groups compared with placebo at all time points. Tibolone was well tolerated, with a similar overall incidence of adverse events compared with placebo. Tibolone 1.25 mg per day is recommended because it shows a positive and statistically significant change in BMD of spine and femoral neck.", "To determine the influence of the use of tibolone on the frequency of flares of systemic lupus erythematosus (SLE) in postmenopausal patients.\n Thirty patients with inactive or controlled SLE were included in the study. Patients were randomized to receive a 12-month course of either tibolona (2.5 mg/day) or placebo. The following were investigated: hypoestrogenism symptoms by Kupperman index, weight; anti-dsDNA antibodies; SLE flares (frequency) assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and biochemical profile (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, complement components [C3/C4], alpha1-acid glycoprotein, urea, creatinine, 24-h proteinuria, C-reactive protein and erythrocyte sedimentation rate).\n The reduction in Kupperman index was greater in the patients using tibolone than in those using placebo. The mean SLEDAI was not different between the groups during the study as well as SLE flare frequency (tibolone: 2/15 [13.3%] vs. placebo: 1/15 [6.7%]; p=0.54). All cases of flares were considered mild to moderate. Although the groups were similar at the baseline evaluation, after 6 and 12 months of treatment lower values were found in the tibolone group for triglycerides (6 months: 161.6+/-30.9 mg/dl vs. 194.4+/-46.5; p=0.04; 12 months 163.7+/-29.8 mg/dl vs. 204.1+/-49.9 mg/dl; p=0.02; tibolone vs. placebo group, respectively) and for HDL-C (6 months: 40.7+/-10.7 mg/dl vs. 53.4+/-16.5; p=0.02; 12 months: 47.2+/-7.9 mg/dl vs. 63.2+/-16.3mg/dl; p<0.01; tibolone vs. placebo group, respectively). There were no differences between the two groups in any of the remaining variables.\n In patients with inactive or stable SLE, the short-term use of tibolone did not significantly affect the frequency of flares. In addition, tibolone was well tolerated and effective to control hypoestrogenism related symptoms in SLE patients.", "tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints, without affecting endometrial thickness and lipid profile or blood glucose. However, the potentially similar efficacy, but better tolerability, of a low dose of this drug (1.25 mg) has never been established.\n 162 healthy, non-obese, post-menopausal women, aged 40-65 years, with an intact uterus were enrolled in a national, single centre, randomised, double blind, placebo controlled, parallel group trial. After 1 week of runin, patients were treated for 24 weeks with placebo, tibolone 1.25 mg or 2.5 mg/day. During the study laboratory tests, endometrial ultrasound scans and mammography were performed. Occurrence of menopausal signs and symptoms, including vaginal bleeding, and quality of sexual life were also checked.\n in the 120 patients terminating the study without major protocol violations, climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg (78% and 90% reduction at week 24 for hot flushes, 36% and 34% for sweating episodes and 44% and 51% for vaginal dryness), but not by placebo. Benefits occurred earlier in the group treated with tibolone 2.5 mg. Quality of sexual life was almost invariably improved by tibolone as compared to placebo, but improvement occurred earlier in the tibolone 1.25 mg group. Severity of vaginal bleeding was not different between placebo and active treatment groups, except at week 12 when was higher. At the end of treatment vaginal bleeding occurred in 15% of patients treated with placebo, 14% treated with tibolone 1.25 mg and 12% treated with tibolone 2.5 mg. Endometrial thickness and breast density were not changed by treatment, as well as FSH, 17-beta-estradiol, total cholesterol, HDL and LDL cholesterol, triglycerides and blood glucose. Adverse events were reported by 14.7%, 26.7% and 24.4% of patients treated with placebo, tibolone 1.25 mg and tibolone 2.5 mg/day, respectively.\n tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles, though were more effective than placebo. Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function.", "The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women.\n Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale.\n Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse.\n The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT.", "To compare transvaginal ultrasonography with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy and to evaluate endometrial safety of three hormone replacement therapy regimens.\n In a randomized, comparative study in postmenopausal women, endometrial safety was evaluated using (1) no hormone replacement therapy, (2) oral micronized 17 beta-estradiol/oral sequential dydrogesterone, (3) transdermal 17 beta-estradiol/oral sequential dydrogesterone, or (4) oral tibolone. 85 Non-hysterectomised subjects underwent transvaginal ultrasonography immediately before Pipelle biopsy at baseline and subsequently after 12 and 24 months. Endometrial thickness and uterine dimensions were determined by transvaginal ultrasonography, and endometrial thickness (double-layer) was compared with biopsy results.\n Endometrial evaluation was conveniently performed by transvaginal ultrasonography, and endometrial thickness correlated well with biopsy findings. If endometrial thickness was < 5 mm, the endometrial biopsy sample was either inactive/atrophic or insufficient for histopathological diagnosis. Hyperplastic or malignant changes were not reported. After 24 months, endometrial thickness was increased both in the oral (P < 0.001) and transdermal (P < 0.001) 17 beta-estradiol/dydrogesterone groups, whereas with tibolone the change in endometrial thickness was not different from controls.\n transvaginal ultrasonography of the endometrium reliably predicts the histological picture in hormone replacement therapy users. Using 5 mm endometrial thickness as cut-off point, more than 75% of biopsies could be avoided. All three hormone replacement therapies were safe with respect to the endometrium. With sequential 17 beta-estradiol/dydrogesterone the expected progestogen-induced secretory pattern was observed, whereas endometrial histology under tibolone closely mimicked the natural atrophic postmenopausal state.", "To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas.\n In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared.\n Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size.\n The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth.", "To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women.\n In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups.\n Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups.\n Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms.", "To compare compliance, symptom control, bleeding patterns, lipid and biochemical changes in postmenopausal women treated with three regimens of HRT.\n In a prospective, randomised, group comparative study, with 165 patients, the effects on the aforementioned parameters, as well as treatment compliance and side effects were studied with oral tibolone 2.5 mg per day, with cyclic combined regimen of transdermal oestrogen and progestogen (transdermal patch of 17beta-oestradiol 50 microg/day during 14 days and transdermal patch of 17beta-oestradiol 50 microg/day plus 0.25 mg/day NETA during the following 14 days), and with intermittent progesterone regimen (transdermal 17beta-oestradiol 50 microg/day and oral micronised natural progesterone 200 mg twice a week). Statistical analysis was carried out using the Fisher-test, analysis of the variance (ANOVA) and the Bouferoni test.\n Ten women dropped out of the tibolone group, 11 dropped out of the intermittent dosing group and 21 dropped out of the cyclid combined group. Irregular bleeding occurred at more rates in the cyclid combined group. Similar reductions in climacteric symptoms were found in the three groups. No differences were observed with respect to biochemical analysis.\n Efficacy and safety of the three treatment regimens being comparable, but the patients in our study preferred those that did not produce bleeding episodes.", "To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day.\n In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean +/- standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test.\n One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group.\n Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.", "To compare the effect of different formulations of continuous combined hormone therapy on sexual performance in naturally postmenopausal women.\n A total of 158 postmenopausal women were enrolled and prospectively randomized to the single-blind study. Fifty-four women received tibolone 2.5 mg, 53 received 2 mg estradiol and 2 mg dienogest (E2/dienogest), and 51 did not receive any menopausal therapy. The patients were monitored after 6 months. Attitudes of sexuality were evaluated by using the Rosen's female sexual function index.\n Compared with E2/dienogest and the control group, tibolone treatment was associated with more improvement of sexual performance, including sexual desire, sexual arousal and satisfaction. Both of the hormone therapies decreased frequencies of vaginal dryness and painful intercourse.\n Tibolone has more positive effects on the sexual dysfunction of postmenopausal women and may be an alternative to the E2/dienogest preparation in postmenopausal women with sexual dysfunction.", "Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but its effect on cancer recurrence is unknown. The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints.\n Between July 11, 2002, and Dec 20, 2004, women surgically treated for a histologically confirmed breast cancer (T(1-3)N(0-2)M(0)) with vasomotor symptoms were randomly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries. Randomisation was done by use of a centralised interactive voice response system, stratified by centre, with a block size of four. The primary endpoint was breast-cancer recurrence, including contralateral breast cancer, and was analysed in the intention-to-treat (ITT) and per-protocol populations; the margin for non-inferiority was set as a hazard ratio of 1.278. This study is registered with ClinicalTrials.gov, number NCT00408863.\n Of the 3148 women randomised, 3098 were included in the ITT analysis (1556 in the tibolone group and 1542 in the placebo group). Mean age at randomisation was 52.7 years (SD 7.3) and mean time since surgery was 2.1 years (SD 1.3). 1792 of 3098 (58%) women were node positive and 2185 of 3098 (71%) were oestrogen-receptor positive. At study entry, 2068 of 3098 (67%) women used tamoxifen and 202 of 3098 (6.5%) women used aromatase inhibitors. The mean daily number of hot flushes was 6.4 (SD 5.1). After a median follow-up of 3.1 years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001). Results in the per-protocol population were similar (209 of 1254 [16.7%] women in the tibolone group had a recurrence vs 138 of 1213 [11.4%] women in the placebo group; HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Tibolone was not different from placebo with regard to other safety outcomes, such as mortality (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10, respectively), or gynaecological cancers (10 vs 10, respectively). Vasomotor symptoms and bone-mineral density improved significantly with tibolone, compared with placebo.\n Tibolone increases the risk of recurrence in breast cancer patients, while relieving vasomotor symptoms and preventing bone loss.\n Schering-Plough (formerly NV Organon, Oss, Netherlands).", "The present randomized prospective study aimed to compare the effect of tibolone (T) with conventional low-dose estrogen-progestogen therapy (EPT) administered in a combined continuous regimen on the course of primary headaches in postmenopausal women requesting hormone therapy (HT) for climacteric complaints.\n Forty women presenting for clinical evaluation of headache (migraine without aura and episodic tension-type headache) were enrolled. The observational period lasted 7 months during which women kept a diary of the clinical characteristics of headache attacks and analgesic use. Climacteric symptoms and both anxiety and depression were also measured. After a 1-month run-in period, women received two different HT regimens: 1 mg 17beta-estradiol + 0.5 mg norethisterone acetate (EPT) or 2.5 mg T. Follow-up evaluations were planned after 3 and 6 months of treatment.\n Although T did not affect the number of days with migraine without aura, it significantly reduced the number of hours during which pain intensity prohibited daily activities (P < 0.001) and the number of analgesics (P < 0.001) after 3 months. Conventional low-dose EPT administered in a combined continuous regimen was confirmed to have a mild, but negative, effect on the course of migraine without aura by increasing the number of days with head pain (P < 0.001) and the number of analgesics (P < 0.001). Interestingly, both treatments were effective in the management of episodic tension-type headache, significantly reducing the number of days with head pain, severity, and analgesic consumption.\n In postmenopausal headache sufferers, analgesics are more effective in alleviating severe head pain when women are treated with T in comparison with low-dose EPT for climacteric complaints.", "To compare the effects of tibolone with those of conventional hormone replacement therapy on climacteric symptoms and sexual function in postmenopausal women.\n In a randomized, controlled trial, 140 postmenopausal women were allocated into three groups. Of the subjects included, 47 women received 2.5 mg tibolone + one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily; 46 women received 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone (CEE/MPA) + one Cal+D tablet daily; and 47 women received only one Cal+D tablet as the control group. The Greene Climacteric Scale (GCS) questionnaire was used to detect the efficacy of treatment on climacteric symptoms. Rosen's Female Sexual Function Index (FSFI) was used for sexual function evaluation. Sex hormone binding globulin (SHBG), free estradiol index (FEI) and free testosterone index (FTI) were measured before and after treatment. The women were followed up for 6 months\n After treatment, all subscores in the GCS improved in the tibolone and CEE/MPA groups (p < 0.01), except the sexual subscore in the CEE/MPA group, compared with baseline. There were significant differences in the FSFI in the tibolone and CEE/MPA groups in comparison to the control group after treatment. Tibolone, in comparison to CEE/MPA, significantly lowered SHBG levels and increased the FTI and FEI and improved the desire, arousal and orgasm sexual domains of the FSFI (p < 0.001).\n Tibolone may be an alternative to conventional hormone replacement therapy in the treatment of climacteric symptoms and sexual dysfunction in postmenopausal women.", "Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron, 2 x 5 mg daily for 12 days each month).\n One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months.\n With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group.\n Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.", "To demonstrate the safety and efficacy of tibolone (1.25 and 2.5 mg) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy.\n A placebo-controlled, double-blind, randomized, multicenter study was conducted on 396 healthy postmenopausal women experiencing a minimum of 7 moderate to severe hot flashes per day (60 per week). Participants were randomized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12 weeks. Assessments were done at weeks 4, 8, and 12. The severity and frequency of hot flashes were recorded in patient diaries on a daily basis.\n Tibolone 2.5 mg significantly (P < 0.001) reduced the average number of hot flashes compared with placebo at week 4 (-7.82 vs -5.27), week 8 (-9.71 vs -5.86), and week 12 (-10.14 vs -5.85). The difference between tibolone 1.25 mg and placebo was significant (P < 0.001) at week 8 (-7.96) and week 12 (-8.32). Findings for the average daily severity of hot flashes were similar, with significantly greater reductions at week 4 (P < 0.05) and weeks 8 and 12 (P < 0.001) for tibolone 2.5 mg versus placebo and at weeks 8 and 12 for tibolone 1.25 mg versus placebo (P < 0.001). A menopausal atrophic symptom questionnaire revealed that tibolone 2.5 mg significantly (P < 0.05) reduced nocturia compared with placebo at weeks 4, 8, and 12 and urinary urgency at week 4. Compared with placebo, both doses of tibolone also significantly (P < 0.001) increased the vaginal maturation value from baseline. The overall incidence of adverse events was similar in all treatment groups.\n Tibolone is effective and well tolerated for the treatment of moderate to severe vasomotor symptoms and the effects of vaginal atrophy associated with menopause.", "To examine the effect of tibolone, a synthetic steroid with tissue-specific activity, on quality of life in a randomised, double-blind, placebo-controlled study in healthy postmenopausal women.\n A total of 85 women (54.2+/-4.7 years), were randomised to 2.5 mg tibolone (Livial) or to identically appearing placebo pills daily for 12 months. Quality of life was assessed with the Nottingham Health Profile (NHP). Also, information on the occurrence of climacteric complaints and incidences of vaginal bleeding/spotting was gathered.\n Compared to baseline values, the tibolone group significantly improved on three out of six NHP domains: overall 46.8-25.3, emotional reactions 6.8-2.9 and sleep 19.0-7.2. In the placebo group a significant difference from baseline was observed on the 'physical mobility' parameter: 6.9-3.0. Significant between-group difference was only reached on the domains 'sleep': tibolone 7.2 versus placebo 15.2 and 'physical mobility': tibolone 3.8 versus placebo 3.0. The occurrence of hot flushes and nightly sweats was significantly lower in the tibolone group compared to placebo after 12 months of treatment. Throughout the study period a total of four women in the placebo, compared to 16 women in the tibolone group, reported vaginal bleeding/spotting.\n A trend favouring tibolone was observed. However, improvements from baseline were only reflected in a significant between-group difference on the domains of sleep and physical mobility. The limited sample size might have caused this ambiguity. Further research in a larger population is recommended to clear this inconsistency.", "To compare the incidence of vaginal spotting/bleeding events and breast pain between therapy with tibolone 2.5 mg and continuous combined transdermal estradiol (E(2))/norethisterone acetate (NETA) 50 microg/140 microg after 24 weeks of treatment.\n A double-blind, double-dummy, randomized, controlled trial was performed and assessments were performed at baseline, week 12 and week 24. Bleeding/spotting events were recorded in a daily diary. Breast signs and symptoms were collected as adverse events.\n A total of 403 women (mean age 56 years) were randomized. Bleeding/spotting events during weeks 1-12 with tibolone and E(2)/NETA were experienced by 16% and 56% of women, respectively (p < 0.001). The corresponding percentages during weeks 13-24 were 12% and 51%, respectively (p < 0.001). E(2)/NETA was significantly more likely than tibolone to be associated with vaginal hemorrhage (11% vs. 0%; p < 0.001) and breast signs and symptoms (11% vs. 4%; p = 0.015). Early discontinuations resulting from adverse events were significantly more common in the E(2)/NETA group than in the tibolone group (20% vs. 12%), primarily related to withdrawal due to vaginal hemorrhage (8% vs. 0%).\n Tibolone has a significantly better tolerability profile than transdermal E(2)/NETA as measured by vaginal bleeding, breast pain and treatment continuation.", "Most previous studies designed to evaluate the efficacy of hormone replacement therapy (HRT) have been carried out in Europe, North America and Australia, involving Caucasian women for 6 months or less.\n To evaluate the 12-month effects of two different HRT regimens on postmenopausal symptoms of Middle-Eastern women.\n Hundred healthy Libyan women with postmenopausal symptoms, 12 months or more since their last menstrual period, were enrolled in a 12-month prospective study. Participants were randomly prescribed one of the two formulations, 50 in each group. These regimens were a continuous regimen of tibolone 2.5 mg oral tablets and a continuous regimen of 17beta-oestradiol sequentially combined with dydrogesterone (2/10 mg) oral tablets. The presence and severity of short- and intermediate-term symptoms were reported at 0, 3, 6 and 12 months of treatment. Observed symptoms were hot flushes, night sweating, palpitations, insomnia, depression, nervousness, loss of memory, vaginal dryness, loss of libido and joint pain.\n Forty-nine women (98%) in each group completed the 12-month study period. Participants, in the two groups, experienced a significant improvement within the first 3 months of treatment. The observed symptoms were completely relived by the sixth month without any significant difference between the two groups. Improvements were sustained over the 12-month period of the study. HRT users showed their acceptance to the two regimens.\n Tibolone and 17beta-oestradiol/dydrogesterone oral tablets were effective and safe to treat short- and intermediate-term symptoms in Middle-Eastern postmenopausal women, within 6 months, and with no significant differences between the groups. Thus, the use of HRT to relieve menopausal symptoms is highly recommended, at least in this region.", "to compare the effects of tibolone 2.5 mg (Livial) with those of 17 beta-estradiol 2 mg plus norethisterone acetate 1 mg (Kliogest) on sexual life.\n in a 48 week, double blind, multicenter study, 437 postmenopausal women were randomised to treatment with either tibolone or 17 beta-estradiol 2 mg plus norethisterone acetate. Treatment groups were compared with respect to different aspects of sexual life with a questionnaire covering sexual experience and responsiveness during the last 30 days.\n a total of 315 subjects completed 48 weeks treatment. In the E2/NETA group an improvement after 48 weeks compared to baseline was observed in five out of seven items assessing sexual life. In the tibolone group an improvement regarding all seven items assessing sexual life was seen. When tibolone was compared to E2/NETA significantly higher scores were found for the items assessing 'frequency', 'satisfaction' and 'enjoyment'.\n this study indicate that tibolone and E2/NETA -which both have an androgenic profile-affect several aspects of sexual life positively. The difference with respect to satisfaction with sexual enjoyment and frequency could be of clinical importance." ]

[ "8977608", "4567320" ]

[ "Comparison of the acute effects on gas exchange of nasal ventilation and doxapram in exacerbations of chronic obstructive pulmonary disease.", "Respiratory stimulation with intravenous doxapram in respiratory failure. A double-blind co-operative study." ]

[ "Nasal intermittent positive pressure ventilation (NIPPV) is useful in exacerbations of chronic obstructive pulmonary disease (COPD) complicated by ventilatory failure. The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure.\n Patients admitted with acute exacerbations of COPD and type 2 respiratory failure (Pao2 < 8 kPa and PaCO2 > 6.7 kPa) who did not improve with conventional treatment were randomised to receive either NIPPV or intravenous doxapram. Blood gas tensions were monitored for four hours.\n In nine patients who received NIPPV the arterial PaO2 improved from a mean (SE) of 5.9 (0.4) kPa to a maximum of 8.1 (0.6) kPa which was maintained at four hours. Eight patients who received doxapram had a similar baseline Pao2 of 5.6 (0.4) kPa which rose to a maximum of 7.3 (0.5) kPa but this was not maintained at four hours. The improvement in Pao2 in patients on NIPPV was accompanied by a fall in Paco2 but, in contrast, in those who received doxapram there was no improvement in Paco2.\n NIPPV may be more effective than doxapram in the management of acute ventilatory failure complicating COPD.", "nan" ]

[ "12410192", "15695300", "15452689", "15265162", "15690187", "2060176", "15784715", "16282699", "11014345" ]

[ "Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial.", "Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment.", "The efficacy of acute administration of pamidronate on the conservation of bone mass following severe burn injury in children: a double-blind, randomized, controlled study.", "Treatment of osteopenia and osteoporosis in renal transplant children and adolescents.", "Pamidronate treatment of pediatric fracture patients on chronic steroid therapy.", "Treatment and prevention of osteoporosis in juvenile chronic arthritis with disodium clodronate.", "Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial.", "Pamidronate therapy for preventing steroid-induced osteoporosis in children with nephropathy.", "Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study." ]

[ "To evaluate in a double-blind, placebo-controlled clinical trial the safety and efficacy of intravenous pamidronate to treat osteopenia in nonambulatory children with cerebral palsy.\n Six pairs of subjects generally matched within each pair for age, sex, and race completed the protocol. One member of each pair randomly received plain saline placebo, the other pamidronate. Drug/placebo was administered intravenously daily for 3 consecutive days, and this 3-day dosing session was repeated at 3-month intervals for one year. Evaluations were continued for 6 months after the year of treatment. Bone mineral density (BMD) was measured in the distal femur, a site specifically developed for use in this contracted population, and the lumbar spine.\n In the metaphyseal region of the distal femur, BMD increased 89% +/- 21% (mean +/- SEM) over the 18-month study period in the pamidronate group compared with 9% +/- 6% in the control group. Age-normalized z scores increased from -4.0 +/- 0.6 to -1.8 +/- 1.0 in the pamidronate group and did not significantly change in the control group (-4.2 +/- 0.3 to -4.0 +/- 0.3). The first dosing with pamidronate caused a transient drop in serum calcium that was asymptomatic and not treated. No other potentially adverse effects were noted.\n In this small controlled clinical trial, pamidronate was found to be a safe and very effective agent to increase BMD in nonambulatory children with cerebral palsy.", "To determine the effects of once-weekly oral alendronate on indices of bone size, density and resorption in children with chronic illness being treated with glucocorticoids.\n Twenty-two children with chronic illness treated with prednisone were randomized to receive 1 year's treatment with either once-weekly oral placebo or alendronate (1-2 mg/kg body weight) in a double-blind study. The main outcome measures were changes in lumbar spine and femoral shaft size and volumetric density (measured by dual energy X-ray absorptiometry) and N-telopeptide excretion (a marker of bone resorption).\n Once-weekly alendronate was well tolerated, and there were no major adverse events. In both groups bone size and bone mineral content increased through growth. Volumetric bone density of the lumbar spine increased significantly in the alendronate group (P = 0.013), but not in the placebo group. There were no differences between the groups in growth in the cortical width of the femoral shaft, but the cross-sectional moment of inertia per unit length-a derived estimate of mechanical strength-increased significantly in the alendronate group (P = 0.014) but not in the placebo group. Urine N-telopeptide excretion was suppressed significantly in the alendronate group (P = 0.007) but not in the placebo group. Height velocity was positively correlated with changes in both lumbar spine area and the total width of the femoral shaft (P = 0.015, P = 0.026, respectively).\n Once-weekly oral alendronate is well tolerated, suppresses bone resorption and may improve volumetric bone density at the lumbar spine and mechanical strength of the femoral shaft in children with chronic illness taking glucocorticoids. It does not affect bone growth. Larger controlled studies are needed to determine if these changes translate into reduced fracture incidence or greater peak bone mass. This study highlights the importance of differentiating between changes in bone size and changes in volumetric bone density in assessing bone in children, and also having control subjects in intervention studies.", "Bone loss is a known complication of severe burn injury. It is, in part, due to increased endogenous glucocorticoids that contribute to the reduction in bone formation and osteoblast differentiation, hypercalciuria secondary to hypoparathyroidism, and vitamin D deficiency. In this study we attempted to prevent post-burn bone loss by acute intravenous administration of the bisphosphonate pamidronate. We enrolled 43 children, with burns of > 40% total body surface area, in a randomized, double-blind, placebo-controlled study, administering the study drug within 10 days of burn injury and again 1 week later. Dual energy X-ray absorptiometry was performed prior to drug therapy, at hospital discharge and at 6 months post-burn. Urine specimens were obtained at baseline and discharge for determination of calcium and free deoxypyridinoline. Blood was obtained along with the urine specimens for measurement of intact parathyroid hormone (iPTH) and ionized calcium (Ca) levels. Following doxycycline labeling, intra-operative iliac crest bone biopsies were obtained, and bone histomorphometry was determined. At time of discharge there were no differences in total body bone mineral content (BMC), but lumbar spine BMC was significantly higher in the pamidronate group (P < 0.005). By 6 months post-burn the differences in lumbar spine BMC persisted, but, now, total body BMC was significantly higher in the pamidronate group (P < 0.05). Bone histomorphometry and levels of urine Ca and free deoxypyridinoline failed to show significant increases in bone formation or decreases in bone resorption. Pamidronate did not exacerbate the hypocalcemia in burn patients. In summary, acute intravenous pamidronate administration following burns may help to preserve bone mass, perhaps by inhibiting the glucocorticoid-induced apoptosis of osteoblasts and osteocytes.", "Successful renal transplantation corrects many of the metabolic abnormalities associated with the development of renal osteodystrophy, but despite a well-functioning graft osteopenia, growth failure, spontaneous fractures, and avascular necrosis remain prevalent in adult and pediatric kidney recipients. A paucity of information exists regarding the effects of different therapies to prevent and treat bone loss in the renal transplant recipients. We constructed a design to study the effect of different modalities of treatment on bone mass in our renal transplant children. Among 93 patients who underwent renal transplantation at the age of 17 yr or less and were subjected to dual-energy X-ray absorptiometry (DEXA), we blindly randomized 60 patients who had osteopenia or osteoporosis (T-score = -1 by DEXA) in a prospective study. Their mean age at time of transplantation was 13.4 +/- 4.3 yr. The mean duration after transplantation was 48 +/- 34 months. The patients were classified randomly into four groups. Each group consisted of 15 patients: group 1 was the control group, group 2 received oral alfacalcidol 0.25 microg daily, group 3 received oral alendronate 5 mg daily, and group 4 received 200 IU/day nasal spray calcitonin. Parameters of bone turnover, calcium metabolism, and DEXA were measured before and after 12 months of treatment duration. The characteristics of all groups were comparable at the beginning of the study. At the lumber spine, bone mass density decreased from -2.4 to -2.8 in group 1, increased from -2.3 to -0.5 in group 2, from -2.3 to -1.9 in group 3, and from -2.3 to -1.0 in group 4. The four groups had similar patient profiles, serum creatinine, intact parathyroid hormone, osteocalcin, and deoxypyridinoline. This study confirmed the value of alfacalcidol and antiresorptive agents in the treatment of osteopenia and osteoporosis in young renal transplant recipients.These therapies were safe, tolerable, simple to administer and potentially applicable to other renal transplant patients.\n Copyright 2004 Blackwell Munksgaard", "Pediatric nephrology and rheumatology patients with steroid-induced osteopenia are at risk of skeletal fracture. Bisphosphonate therapy has not been routinely advocated as a primary or secondary intervention for steroid-associated fractures in this population. This case control study evaluates the role of pamidronate therapy as a secondary fracture intervention. Children with symptomatic pathological fractures of the axial spine or ribs were treated with pamidronate 1 mg/kg/dose (n=17) IV at 60-day intervals for 1 yr (n=15) or 2 yr (n=2). Bone mineral density of L1-L4 (BMD) was assessed prior to treatment and at six-month intervals, and compared to 17 disease-age-gender-steroid dose-matched control patients. Alkaline phosphatase, calcium, phosphate, PTH, renal biochemistry, and 24-hr urine collections for CrCl, N-telopeptide/creatinine ratio, phosphate excretion, and calcium excretion were obtained every two months in the pamidronate population. Pamidronate caused a first exposure transient flu-like illness lasting <24 h in three patients and one patient had a new pathological fracture. No adverse events of hypocalcemia, allergic reaction or thrombophlebitis were noted. All patients reported improvement of skeletal pain. Despite ongoing steroid treatment, pamidronate significantly increased L1-L4 BMD Z-scores (mean+/-SE) relative to baseline (pamidronate vs control: 0-6 months: 0.27+/-0.14 vs -0.82+/-0.31; 0-12 months: 0.63+/-0.17 vs -0.46+/-0.27; 0-18 months: 0.55+/-0.32 vs 0.17+/-0.27; 0-24 months: 0.15+/-0.21 vs -0.23+/-0.22; 0-30 or 36 months: 0.77+/-0.71 vs -0.68+/-0.25) with repeated measures ANOVA assessment (F=11.27, p=0.0057). This study supports the safety and efficacy of pamidronate in steroid-induced fractures in pediatric nephrology and rheumatology patients.", "Osteoporosis is one of the most difficult problems in the management of Chronic Juvenile Arthritis (JCA). The available data suggest that bone loss results from multifactorial processes which lead to bone degradation through the activation of osteoclasts. Biphosphonates are synthetic factors that, once localized on the surface of hydroxyapatite crystals, do not allow either the production or destruction of the crystals. This activity seems to be due to cytotoxicity against osteoclasts and to inhibition of prostaglandin E2 synthesis. There is some evidence that these drugs are effective in the treatment of osteoporosis in several diseases. In an attempt to reduce or prevent osteoporosis in children affected by JCA we started a trial with disodium clodronate, a type of biphosphonate. Thirteen patients were enrolled in the study: 7 received disodium clodronate and 6 acted as control subjects. Before starting the therapy and after one year we performed a CT scan to evaluate the mineral bone density in all patients. The mean bone density increased from a bone mineral content of 129 mg/cc before treatment to 134 mg/cc after treatment (8% increase); control patients passed from 123 mg/cc to 115 mg/cc (7% decrease) in the same period. Only one child stopped treatment because of gastrointestinal side effects. The small number of patients enrolled in the trial does not allow any definite conclusions to be drawn, but the data are interesting and worthy of further study.", "Osteopenia is a serious medical complication of anorexia nervosa, with no known effective treatment. We conducted a double-blinded, randomized trial comparing alendronate (10 mg daily) with placebo in 32 adolescents with anorexia nervosa (mean age, 16.9 +/- 1.9 yr). All subjects received 1200 mg elemental calcium and 400 IU vitamin D daily and received the same multidisciplinary treatment for their eating disorder. Bone mineral densities (BMDs) of the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry at baseline and after 1 yr of treatment. Twenty-nine subjects completed the study. Femoral neck and lumbar spine BMDs increased 4.4 +/- 6.4% and 3.5 +/- 4.6% in the alendronate group compared with increases of 2.3 +/- 6.9% and 2.2 + 6.1% in the control group (P = 0.41, femoral neck; P = 0.53, lumbar spine). From baseline to follow-up, BMD increased significantly at the femoral neck (P = 0.02) and lumbar spine (P = 0.02) in those receiving alendronate, but did not increase in those assigned placebo (P = 0.22, femoral neck; P = 0.18, lumbar spine). At follow-up, body weight was the most important determinant of BMD. BMD was significantly higher in subjects who were weight-restored compared with those who remained at low weight (P = 0.002, femoral neck; P = 0.04, lumbar spine). After controlling for body weight, treatment group assignment still had an independent effect at the femoral neck. We conclude that in adolescents with anorexia nervosa, weight restoration is the most important determinant of BMD, but treatment with alendronate did increase the BMD of the lumbar spine and femoral neck within the group receiving alendronate, but not compared with placebo in the primary analysis. Until additional studies have demonstrated efficacy and long-term safety, the use of alendronate in this population should be confined to controlled clinical trials.", "Steroid-induced osteoporosis (SIO) is a serious complication of long-term steroid therapy and is of particular concern in growing children. Recently bisphosphonates have been applied in the treatment or prevention of SIO. We investigated the efficacy of pamidronate on SIO in childhood nephropathy patients receiving long-term corticosteroid therapy.\n Forty-four children receiving high doses of steroids were enrolled in the study. There was no history of bone, liver, or endocrine disease. Patients were randomly classified into two groups, the control group and the study group. All patients received corticosteroids for 3 months. Control group took oral calcium supplements (500 mg/day) only, and the study group oral calcium and pamidronate (125 mg) for 3 months. Biochemical tests, long bone radiography, and bone mineral density (BMD) were performed in the first month and 3 months later in all patients.\n The differences in the results of biochemical tests such as serum calcium, BUN, and creatinine level obtained in the first month and three months later were not of statistical significance in both the control and the study groups. However, the mean BMD of the lumbar spine decreased from 0.654 +/- 0.069 (g/cm2) to 0.631 +/- 0.070 (g/cm2) in the control group (p = 0.0017), while it did not in the study group from 0.644 +/- 0.189 (g/cm2) to 0.647 +/- 0.214 (g/cm2).\n Pamidronate appears to be effective in preventing SIO in children with nephropathy requiring long-term steroid therapy. Further long-term follow-up studies regarding the efficacy and side effects appear to be necessary to set a more solid basis for such pediatric uses of bisphosphonates such as pamidronate.\n 2006 S. Karger AG, Basel.", "Osteopenia/osteoporosis is being increasingly reported as a complication of many chronic diseases, even in children. In this preliminary study, we evaluated the effect of an oral bisphosphonate (alendronate) on bone mass in children with diffuse connective tissue diseases.\n Thirty-eight children with low bone mass were treated with alendronate for 1 year; 38 children who had the same primary disorders as the study patients but in a less severe form served as untreated control patients. We were also able to evaluate changes in bone mass (before and after alendronate) in 16 of the treated patients whose bone mineral density (BMD) had been routinely measured before the present study was initiated.\n BMD increased by a mean +/- SD of 14.9 +/- 9.8% (P < 0.002 versus baseline) in the treated patients (reaching the normal range in 13 patients), while the BMD was 2.6 +/- 5% (not significant versus baseline) in the control group (15 had a decrease). Most interestingly, there was a large increase in BMD (15.3 +/-9.9%) after alendronate therapy in the 16 children who had their BMD followed up in the year before the study, during which time they had shown little increase in BMD (1.03 +/- 6.3%), and often a decrease. Considering their condition, increases in the height of all patients was satisfactory. No new fractures were observed after alendronate therapy was initiated.\n Bisphosphonates can be considered essential components of the treatment of secondary osteoporosis, not only in adults, but also in pediatric patients. Alendronate has a positive effect on secondary osteopenia/osteoporosis in children with connective tissue diseases." ]

[ "19862815", "14990647", "19487381", "17868728", "19171708", "18936475", "18006769", "12890841", "17876014", "18467719", "20100962", "16636341", "17538086", "18653228", "20368553", "16104906", "16484699", "15923569", "19451442" ]

[ "Upfront, randomized, phase 2 trial of sorafenib versus sorafenib and low-dose interferon alfa in patients with advanced renal cell carcinoma: clinical and biomarker analysis.", "Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma.", "Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma.", "Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941.", "Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma.", "Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206.", "Phase 2 study of ABT-510 in patients with previously untreated advanced renal cell carcinoma.", "A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer.", "Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer.", "Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.", "Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.", "Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.", "Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.", "Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial.", "Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival.", "A lower dose of thalidomide is better than a high dose in metastatic renal cell carcinoma.", "Randomized phase II study comparing thalidomide with medroxyprogesterone acetate in patients with metastatic renal cell carcinoma.", "Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma--CALGB 69901.", "Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial." ]

[ "The objective of this study was to independently evaluate the objective response rate of sorafenib and sorafenib plus low-dose interferon-alfa 2b (IFN) as frontline therapy in patients with metastatic renal cell carcinoma (mRCC).\n Untreated patients with clear cell mRCC were randomized to receive sorafenib 400 mg orally twice daily or sorafenib 400 mg orally twice daily plus subcutaneous IFN 0.5 million U (MU) twice daily. Primary endpoints included the objective response rate (ORR) and safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the predictive value of tumor tissue biomarkers.\n Eighty patients were enrolled. The median follow-up was 19.7 months (range, 0-34.2 months). The ORR was 30% (95% confidence interval [CI], 16.6%-46.5%) in the sorafenib arm and 25% (95% CI, 12.7%-41.2%) in the combination arm. The median PFS was 7.39 months in the sorafenib-alone arm (95% CI, 5.52-9.20 months) and 7.56 months in the sorafenib plus IFN arm (95% CI, 5.19-11.07 months). The median OS was 27.04 months in the combination arm (95% CI, from 22.31 to not attained) and was not reached in the sorafenib arm. Toxicities were comparable in both arms. In a multivariate model, increased phosphorylated protein kinase B (pAKT) levels were associated with poorer PFS (hazard ratio, 1.04; 95% CI, 1.00-1.08; P = .0411) and OS (hazard ratio, 1.15; 95% CI, 1.02-1.29; P = .0173).\n The addition of low-dose IFN to sorafenib resulted in efficacy outcomes that were comparable to those achieved with sorafenib monotherapy. The current results indicated that pAKT levels may predict for clinical outcome, but further mechanistic study is required.\n Copyright 2010 American Cancer Society.", "To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC).\n Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics.\n CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar.\n In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.", "A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.\n Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-alpha 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up.\n Median overall survival was greater in the sunitinib group than in the IFN-alpha group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-alpha group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-alpha (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%).\n Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy.", "We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents.\n An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model.\n Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 x the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1, 8.5 months in patients with 2 and 3.5 months in patients with 3 or more.\n We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling.", "An open-label, phase II study to evaluate progression-free survival (PFS), overall best response, adverse events (AEs), and patient-reported outcomes with sorafenib versus interferon alfa-2a (IFN-alpha-2a) in patients with untreated, advanced renal cancer.\n A total of 189 patients were randomly assigned to oral sorafenib 400 mg twice daily or to subcutaneous IFN-alpha-2a 9 million U three times weekly (period 1). Sorafenib patients who progressed were dose-escalated to 600 mg twice daily; IFN-alpha-2a patients who progressed were switched to sorafenib 400 mg twice daily (period 2).\n In period 1 PFS was similar for sorafenib-treated (n = 97; 5.7 months) and IFN-alpha-2a-treated patients (n = 92; 5.6 months); more sorafenib-treated patients had tumor shrinkage (68.2% v 39.0%). Common drug-related AEs (Grades > or = 3) for sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and rash/desquamation (6.2%); for IFN-alpha-2a, these were fatigue (10.0%), nausea (3.3%), flu-like syndrome (2.2%), and anorexia (2.2%). Sorafenib-treated patients reported fewer symptoms, better quality of life (QOL), and greater treatment satisfaction. In period 2, 41.9% of patients who received sorafenib 600 mg twice daily (n = 43) experienced tumor reduction (median PFS, 3.6 months). After the switch to sorafenib 400 mg twice daily, tumors were reduced in 76.2% of 50 patients (median PFS, 5.3 months). AEs were mostly grade 1 to 2; no increase in AEs of grades > or = 3 occurred after sorafenib dose escalation.\n In this study, sorafenib resulted in similar PFS as IFN-alpha-2a in patients with untreated RCC. However, sorafenib-treated patients experienced greater rates of tumor size reduction, better QOL, and improved tolerability. Both dose escalation of sorafenib after progression and a switch to sorafenib after progression on IFN-alpha-2a resulted in clinical benefit.", "Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted.\n Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety.\n Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%).\n Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.", "Angiogenesis is a characteristic of renal cell carcinoma. ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1. This study was designed to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma.\n Patients with previously untreated metastatic or unresectable renal cell carcinoma were randomized to treatment with one of two doses of ABT-510, self-administered s.c. twice daily in 28-day treatment periods without intervening rest periods. End points were progression-free survival (PFS), objective response rate, overall survival, and toxicity.\n The objective response rate was 4% in the 10 mg twice daily group, and there were two unconfirmed PRs in the 100 mg twice daily group. Respective median PFS was 4.2 and 3.3 months, with a 6-month PFS of 39% and 32%. Median overall survival was 27.8 months (10 mg twice daily) and 26.1 months (100 mg twice daily). The most frequent adverse events were injection site reactions (84%), fatigue (50%), headache (20%), and nausea (19%). The incidence of treatment-related, grade 3/4 adverse events was low and included three bleeding episodes (gastrointestinal hemorrhage, intracranial hemorrhage, and hemoptysis) and one thrombotic event (deep vein thrombosis). No deaths were attributed to ABT-510.\n There was little evidence of clinical activity for ABT-510, and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted. The evidence of a favorable safety profile may justify further evaluation in combination therapy.", "Mutations in the tumor-suppressor gene VHL cause oversecretion of vascular endothelial growth factor by clear-cell renal carcinomas. We conducted a clinical trial to evaluate bevacizumab, a neutralizing antibody against vascular endothelial growth factor, in patients with metastatic renal-cell carcinoma.\n A randomized, double-blind, phase 2 trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks; the time to progression of disease and the response rate were primary end points. Crossover from placebo to antibody treatment was allowed, and survival was a secondary end point.\n Minimal toxic effects were seen, with hypertension and asymptomatic proteinuria predominating. The trial was stopped after the interim analysis met the criteria for early stopping. With 116 patients randomly assigned to treatment groups (40 to placebo, 37 to low-dose antibody, and 39 to high-dose antibody), there was a significant prolongation of the time to progression of disease in the high-dose--antibody group as compared with the placebo group (hazard ratio, 2.55; P<0.001). There was a small difference, of borderline significance, between the time to progression of disease in the low-dose--antibody group and that in the placebo group (hazard ratio, 1.26; P=0.053). The probability of being progression-free for patients given high-dose antibody, low-dose--antibody, and placebo was 64 percent, 39 percent, and 20 percent, respectively, at four months and 30 percent, 14 percent, and 5 percent at eight months. At the last analysis, there were no significant differences in overall survival between groups (P>0.20 for all comparisons).\n Bevacizumab can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer.\n Copyright 2003 Massachusetts Medical Society", "Bevacizumab (Bev) has clinical activity in advanced renal cell carcinoma (RCC), and, when combined with erlotinib (Erl), has shown encouraging objective response rate (ORR) and progression-free survival (PFS). We performed a phase II, randomized, double-blind, multicenter, placebo-controlled trial to assess whether Erl provides additional clinical benefit with regard to PFS and ORR when combined with Bev in first-line treatment of metastatic RCC.\n One hundred four patients received intravenous Bev (10 mg/kg) every 2 weeks in combination with oral Erl (150 mg) or placebo daily. Patients were treated until progression or toxicity.\n A landmark analysis was performed 9 months after enrollment was completed (median follow-up, 9.8 months). Sixty-five patients had discontinued therapy; time to study discontinuation did not differ between the two treatment groups. The median PFS was 9.9 months (Bev + Erl [B+E]) versus 8.5 months (Bev; hazard ratio = 0.86; 95% CI, 0.5 to 1.49; P = .58). ORR (complete plus partial) was 14% (B+E) versus 13% (Bev). One complete response occurred in the B+E group. Median survival was 20 months for B+E but not reached for Bev. The most common grade 3/4 adverse events (> 5% of patients) were hypertension, rash, proteinuria, diarrhea, and hemorrhage. One treatment-related death occurred on study (GI perforation, B+E group).\n The addition of Erl to Bev was well tolerated, but did not provide additional clinical benefit compared with Bev alone. Bev has encouraging clinical activity for previously untreated metastatic RCC patients.", "Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2.\n Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses.\n Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%).\n Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.", "PURPOSE Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. CONCLUSION Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.", "This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma.\n Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with > or = 25% tumor shrinkage continued open-label sorafenib; patients with > or = 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib.\n Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.\n Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.", "Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease.\n In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group.\n Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patients who received interferon alone. Overall survival in the combination-therapy group did not differ significantly from that in the interferon group (hazard ratio, 0.96; 95% CI, 0.76 to 1.20; P=0.70). Median overall survival times in the interferon group, the temsirolimus group, and the combination-therapy group were 7.3, 10.9, and 8.4 months, respectively. Rash, peripheral edema, hyperglycemia, and hyperlipidemia were more common in the temsirolimus group, whereas asthenia was more common in the interferon group. There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group (P=0.02).\n As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival. (ClinicalTrials.gov number, NCT00065468 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. We did a phase III, randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy.\n Patients with metastatic renal cell carcinoma which had progressed on sunitinib, sorafenib, or both, were randomly assigned in a two to one ratio to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Randomisation was done centrally via an interactive voice response system using a validated computer system, and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy, with a permuted block size of six. The primary endpoint was progression-free survival, assessed via a blinded, independent central review. The study was designed to be terminated after 290 events of progression. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00410124.\n All randomised patients were included in efficacy analyses. The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed (101 [37%] events in the everolimus group, 90 [65%] in the placebo group; hazard ratio 0.30, 95% CI 0.22-0.40, p<0.0001; median progression-free survival 4.0 [95% CI 3.7-5.5] vs 1.9 [1.8-1.9] months). Stomatitis (107 [40%] patients in the everolimus group vs 11 [8%] in the placebo group), rash (66 [25%] vs six [4%]), and fatigue (53 [20%] vs 22 [16%]) were the most commonly reported adverse events, but were mostly mild or moderate in severity. Pneumonitis (any grade) was detected in 22 (8%) patients in the everolimus group, of whom eight had pneumonitis of grade 3 severity.\n Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies.", "A phase III trial of bevacizumab combined with interferon alfa-2a (IFN) showed significant improvements in progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC). Here, we report overall survival (OS) data.\n Six hundred forty-nine patients with previously untreated mRCC were randomly assigned to receive bevacizumab (10 mg/kg every 2 weeks) plus IFN (9 MIU subcutaneously three times a week; n = 327) or IFN plus placebo (n = 322) in a multicenter, randomized, double-blind, phase III trial. The primary end point was OS. Final analysis of the secondary end point (PFS) was reported earlier.\n Median OS was 23.3 months with bevacizumab plus IFN and 21.3 months with IFN plus placebo (unstratified hazard ratio [HR] = 0.91; 95% CI, 0.76 to 1.10; P = .3360; stratified HR = 0.86; 95% CI, 0.72 to 1.04; P = .1291). Patients (> 55%) in both arms received at least one postprotocol antineoplastic therapy, possibly confounding the OS analysis. Patients receiving postprotocol therapy including a tyrosine kinase inhibitor had longer median OS (bevacizumab plus IFN arm: 38.6 months; IFN plus placebo arm: 33.6 months; HR = 0.80; 95% CI, 0.56 to 1.13). Tolerability was similar to that reported previously.\n Bevacizumab plus IFN is active as first-line treatment in patients with mRCC. Most patients with mRCC receive multiple lines of therapy, so considering the overall sequence of therapy when selecting first-line therapy may optimize patient benefit.", "To conduct a dose-finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti-angiogenic agent on RCC.\n The 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy.\n Stable disease was achieved in six patients and was seen in both the low-dose and high-dose thalidomide groups. The median overall survival was 9 months. The low-dose thalidomide regimen was better tolerated and patients survived longer than those on the high-dose regimen (16 vs 6 months, P = 0.04)\n The use of low-dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high-dose regimen.", "To investigate escalating doses of thalidomide compared with medroxyprogesterone in patients with metastatic renal cell carcinoma (RCC), who had either progressed after first-line immunotherapy or who were not suitable for immunotherapy.\n Thalidomide was started at 100 mg/d orally (PO) and escalated by 100 mg/d every 2 weeks to the maximum dose of 400 mg/d. Medroxyprogesterone was given at a fixed dose of 300 mg PO daily.\n Sixty patients were entered (thalidomide:medroxyprogesterone = 29:31; median age, 59 [thalidomide], 60 [medroxyprogesterone]; No. of patients assessable for response, 22 [thalidomide], 26 [medroxyprogesterone]). In the thalidomide arm, there was no objective response seen. The best response was SD in three patients lasting 5+, 6+, and 12 months, respectively. All patients in the medroxyprogesterone arm progressed. There was no difference in overall survival between the two arms; median survival in the thalidomide arm was 8.2 months compared with 4.8 months in the medroxyprogesterone arm (P = .62). Hazard ratio was 0.88 (95% CI, 0.67 to 1.94). Median duration of treatment was 73 days (range, 14 to 364 days) in the thalidomide arm, and 84 days (range, 7 to 175 days) in the medroxyprogesterone arm. The high incidence of toxicity in the thalidomide arm, mainly somnolence, constipation, fatigue and paraesthesia, meant that only 30.8% of patients were able to tolerate the maximum dose of 400 mg/d of treatment.\n Thalidomide is not superior to medroxyprogesterone acetate in patients with metastatic RCC. Its risk/benefit ratio does not favor its use in this patient population.", "To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.\n Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.\n A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.\n CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.", "Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported.\n Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated.\n The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib.\n Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC." ]

[ "17012630", "16935685" ]

[ "Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air: A SOMA study.", "Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study." ]

[ "Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting beta2-agonist with as-needed use of a beta2-agonist and corticosteroid combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled beta2-agonist as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) > or =20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis Turbuhaler) 4.5 microg as needed (n = 47) or budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg as needed (n = 45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% CI -4.7- -0.7). In the budesonide/formoterol group, use of > or =4 inhalations x day(-1) of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a beta2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown.", "The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy.\n We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more.\n Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated.\n Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance." ]

[ "9841829", "11292698", "9498468", "12075764", "17313998", "18602960", "10689236", "15982790", "16257098", "9607039", "10899847", "17448578", "3042876", "18554712", "9815355", "12744870", "1682684", "10558970", "11238232", "9498445" ]

[ "Oral, inactivated, whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine: results of the initial evaluation in children. PRIDE Study Group.", "Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.", "Safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli-cholera toxin B subunit vaccine in Egyptian adults.", "Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants.", "Transcutaneous immunization with the heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC): protective efficacy in a double-blind, placebo-controlled challenge study.", "A double-blind, placebo-controlled trial to evaluate the efficacy of PTL-003, an attenuated enterotoxigenic E. coli (ETEC) vaccine strain, in protecting against challenge with virulent ETEC.", "Double-blind, randomized, placebo controlled pilot study evaluating efficacy and reactogenicity of an oral ETEC B-subunit-inactivated whole cell vaccine against travelers' diarrhea (preliminary report).", "Analysis of efficacy of CVD 103-HgR live oral cholera vaccine against all-cause travellers' diarrhoea in a randomised, double-blind, placebo-controlled study.", "Reduced doses of oral killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine is safe and immunogenic in Bangladeshi infants 6-17 months of age: dosing studies in different age groups.", "Safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli vaccine.", "Safety and immunogenicity of two different lots of the oral, killed enterotoxigenic escherichia coli-cholera toxin B subunit vaccine in Israeli young adults.", "Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. Coli diarrhoea of travellers to Guatemala and Mexico.", "Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial.", "Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial.", "Safety, Immunogenicity, and Protective Efficacy of the Whole-Cell/Recombinant B Subunit (WC/rBS) Oral Cholera Vaccine Against Travelers' Diarrhea.", "Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age.", "Prevention of travellers' diarrhoea by oral B-subunit/whole-cell cholera vaccine.", "Lack of prophylactic efficacy of an enteric-coated bovine hyperimmune milk product against enterotoxigenic Escherichia coli challenge administered during a standard meal.", "Dose-dependent circulating immunoglobulin A antibody-secreting cell and serum antibody responses in Swedish volunteers to an oral inactivated enterotoxigenic Escherichia coli vaccine.", "Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli." ]

[ "Two randomized, double-blinded trials assessed the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli (ETEC) plus cholera toxin B subunit vaccine in Egyptian children. Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds. Safety was monitored for 3 days after each dose. Blood was collected before immunization and 7 days after each dose to measure immune responses. Few children reported postdosing symptoms, with no differences in the frequency of symptoms between treatment groups. Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I (100%, 6-12 years; 95%, 2-5 years), coli surface antigen 2 (92%, 6-12 years; 83%, 2-5 years), and coli surface antigen 4 (93%, 6-12 years). Vaccination evoked a >/=4-fold rise in antitoxic IgA and IgG titers in 93% and 81% of children, respectively. In conclusion, the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children, justifying further evaluation in infants.", "We assessed serologic responses to an oral, killed whole-cell enterotoxigenic Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.", "Enterotoxigenic Escherichia coli (ETEC) is the leading cause of bacterial diarrhea in young children in developing countries. The safety and immunogenicity of a killed, oral ETEC vaccine consisting of whole cells plus recombinantly produced cholera toxin B subunit (rCTB) was evaluated in Egypt, which is endemic for ETEC diarrhea. Seventy-four healthy Egyptian adults (21-45 years old) were randomized and received two doses of the ETEC/rCTB vaccine (E003) or placebo 2 weeks apart. The frequency of adverse events after either dose did not differ by treatment group, and no severe adverse events were reported. After vaccination, peripheral blood IgA B cell responses to CTB (100%) and to vaccine colonization factor antigens CFA/I (94%), CS4 (100%), CS2 (81%), and CS1 (69%) were significantly higher than response rates for the placebo group. These favorable results in Egyptian adults indicate that the ETEC/rCTB vaccine is a promising candidate for evaluation in younger age groups in this setting.", "We conducted the first trial to assess the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B-subunit vaccine in children <2 years old.\n Three doses of vaccine or killed E. coli K-12 control were given at 2-week intervals to 64 Egyptian infants, 6 to 18 months old, in a randomized, double blind manner. Adverse events were monitored for 3 days after each dose. Blood was collected before immunization and 7 to 10 days after each dose to assess vaccine-specific serologic responses.\n There was no statistically significant intergroup difference in the percentage of subjects reporting the primary safety endpoint (diarrhea or vomiting) after the first (31%, vaccine; 30%, control) or third (14%, vaccine; 18%, control) dose, whereas there was a trend toward greater reporting in the vaccine group after Dose 2 (36%, vaccine; 18%, control; P = 0.052). The percentage of children showing IgA seroconversion after any dose was higher in the vaccine than the control group for recombinant cholera toxin B-subunit (97% vs. 46%), colonization factor antigen I (61% vs. 18%) and coli surface antigen 4 (39% vs. 4%) (P < 0.001 for each comparison). IgG seroconversion rates in the vaccine and control groups were 97 and 21% to recombinant cholera toxin B-subunit (P < 0.001), 64 and 29% for colonization factor antigen I (P < 0.01), 53 and 21% for coli surface antigen 2 (P < 0.05) and 58 and 4% for coli surface antigen 4 (P < 0.001), respectively. The third vaccine dose was followed by augmented IgG antitoxin titers.\n The oral enterotoxigenic E. coli vaccine was safe and immunogenic in this setting in Egyptian infants.", "An enterotoxigenic Escherichia coli (ETEC) vaccine could reduce diarrhea among children in developing countries and travelers to these countries. The heat-labile toxin (LT) of ETEC is immunogenic but too toxic for oral or nasal vaccines.\n In a double-blind, placebo-controlled trial, 59 adults were randomized to receive 50 microg of LT or placebo in a patch applied to alternating arms on days 0, 21, and 42. On day 56, 27 vaccinees and 20 controls were challenged orally with 6x10(8) cfu of LT+/ST+ ETEC.\n 100 and 97% of vaccinees had 4-fold increases in anti-LT IgG and IgA, and 100 and 90% developed IgG- and IgA-antibody-secreting cell responses. The study did not meet the primary endpoint: 82% of vaccinees and 75% of controls had moderate to severe ETEC illness. However, vaccinees with ETEC illness had lower numbers (6.8 versus 9.7, p=0.04) and weights of loose stools (840 g versus 1147 g, p<0.05), a decreased need for intravenous fluids (14% versus 40%, p=0.03) and a delayed onset of diarrhea (30 h versus 22 h, p=0.01).\n Transcutaneous LT vaccination induced anti-toxin immune responses that did not prevent but mitigated illness following a high-dose challenge with a virulent LT+/ST+ ETEC strain.", "Enterotoxigenic E. coli (ETEC) are an important cause of diarrhea in developing countries, especially among indigenous children and travelers. In this randomized, double-blind, placebo-controlled trial, a live, attenuated CS1/CS3 ETEC strain, PTL-003, was tested as a potential vaccine strain. Thirty-three subjects drank buffered solutions containing either PTL-003 or placebo on Days 0 and 10 and were challenged with virulent CS1/CS3 ETEC strain E24377A on Day 28. The vaccine did not protect against moderate to severe ETEC illness (the primary endpoint), but it did prime subjects for a rapid antibody response to CS1 and CS3 after challenge, suggesting that a dose of vaccine on Day 28 might improve the immune response to the vaccine. Higher serum anti-CS3 IgA titers at the time of challenge correlated with less severe diarrheal illness.", "Diarrhea caused by enterotoxigenic E.coli (ETEC) is an important health problem in developing countries and in travelers to these areas. In previous trials formulations of ETEC vaccines containing the B-subunit of cholera toxin, which is antigenically similar to the heat labile enterotoxin of ETEC, and the most prevalent colonization factor antigens of ETEC, were shown to stimulate relevant mucosal immune responses in volunteers from Sweden and Egypt.", "Enterotoxigenic Escherichia coli (ETEC), which produces heat labile toxin (LT) and/or heat stable toxin (ST), is considered to be the most common known cause of travellers' diarrhoea (TD). Owing to the antigenic similarity between cholera toxin and LT, immunization with inactivated oral B-subunit/whole-cell cholera vaccine (BS-WC) offers short term (3 months) but significant (>67%) protection against TD caused by LT-related ETEC. Since it expresses the cholera toxin B (CTB) subunit, the live attenuated oral cholera vaccine strain CVD 103-HgR, may induce similar protection. A trial was performed to determine if CVD 103-HgR live oral cholera vaccine would provide a protective efficacy of at least 50% against TD. In addition, the protective efficacy of the vaccine against TD specifically due to LT-ETEC and LT/ST-ETEC was determined. Volunteers (n=134) travelling to Indonesia, India, Thailand or West-Africa were randomised to receive either a placebo (n=65) or the vaccine (n=69). In the placebo group, 46% reported an episode of diarrhoea, compared to 52% in the vaccine group. No significant group differences were found with regard to incidence, duration or severity of all caused TD or ETEC-associated TD. However, ETEC-associated TD occurred earlier in the placebo group (median 5 days), compared to the vaccine group (median 15 days). In conclusion, CVD 103-HgR live oral cholera vaccine failed to provide a 50% protection against TD. This study does not exclude that the vaccine may offer a short-lived protection against ETEC-associated TD. However, the power of the study was limited by the unexpected low incidence of LT-ETEC-associated diarrhoea (9% of all TD) compared to ST-associated TD (24% of all TD).", "The oral-formalin inactivated whole cell enterotoxigenic Escherichia coli (ETEC) vaccine needs to be further tested in developing countries in order to determine the dose at which it will be safe and immunogenic for infants who are the target population for the vaccine. To determine the immunogenicity of reduced doses, studies were first carried out in children, 2-12 years of age (n = 60). The full, half or a quarter doses of the vaccine were comparable in immunogenicity with similar frequency of responses seen to the different antigens (P = NS). Following this result, a pilot study carried out in infants, 6-17 months of age (n = 50), showed that the frequency of episodes of vomiting was lowest when a quarter of the full dose was used. The infants however showed comparable immune responses to the half and quarter dose of vaccine that was tested (P = NS). Based on these results in the infants, a randomized double blind placebo-controlled Phase II study was carried out in 158 children, 6-17 months of age, where a quarter dose of the ETEC vaccine was tested. Adverse events of mild vomiting were seen in only 4% of vaccinees and in 2.5% of placebo recipients. The IgA-antibody secreting cell (ASC) responses to CFA/I (GM: 28.1 ASC/10(7) PBMC) and BS (GM: 55.7 ASC/10(7) PBMC) were elevated compared to placebo recipients (CFA/I-2.0; BS-4.8 ASC/10(7) PBMC) (P = 0.01 to < 0.001). The plasma-IgA antibody titers in vaccinees were also significantly elevated to CFA/I (GM-93.00), CS1 (GM-62.0), CS2 (GM-55.0), CS4 (GM-66.0) and BS (1057.0) compared to preimmune levels or responses or levels in placebo recipients (P < or = 0.05-0.001). This study thus demonstrates that reduced doses of the ETEC vaccine is immunogenic in children and infants as well as safe in infants down to 6 months of age.", "The safety and immunogenicity of two different lots, 001 and 003, of an oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine consisting of a mixture of formalin-killed whole bacteria expressing the most prevalent colonisation factor antigens, i.e. CFA/I, CFA/II and CFA/IV and recombinantly produced cholera B subunit (rCTB) have been evaluated in Swedish volunteers. Neither of the two vaccine preparations, containing different CFA/II-expressing strains but otherwise identical, gave rise to any significant side-effects. Mucosal immune responses, as reflected in antibody-secreting cell (ASC) responses in peripheral blood, were studied after two doses of vaccine and did not differ significantly for the two vaccine lots. Vaccination induced high levels of CTB-specific IgA ASCs in 100% of the volunteers, and significant IgA ASC responses (9- to 36-fold) were noted in 84% of them against CFA/I, in 87% against CFA/II subcomponents CS1-CS3 and in 91% against CFA/IV subfactors CS4 and/or CS5. The frequencies and magnitudes of CFA IgA ASC responses were similar when giving the vaccine with a 1 or 2 week interval. Results from serological analyses showed that the local IgA responses against CFAs are only infrequently associated with serum antibody titre rises.", "Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea among Israeli soldiers serving in field units. Two double-blind placebo-controlled, randomized trials were performed among 155 healthy volunteers to evaluate the safety and immunogenicity of different lots of the oral, killed ETEC vaccine consisting of two doses of whole cells plus recombinantly produced cholera toxin B subunit (rCTB). The two doses of vaccine lot E005 and the first dose of vaccine lot E003 were well tolerated by the volunteers. However, 5 (17%) vaccinees reported an episode of vomiting a few hours after the second dose of lot E003; none of the placebo recipients reported similar symptoms. Both lots of vaccine stimulated a rate of significant antibody-secreting cell (ASC) response to CTB and to colonization factor antigen I (CFA/I) after one or two doses, ranging from 85 to 100% and from 81 to 100%, respectively. The rate of ASC response to CS2, CS4, and CS5 was slightly lower than the rate of ASC response induced to CTB, CFA/I, and CS1. The second vaccine dose enhanced the response to CTB but did not increase the frequencies or magnitude of ASC responses to the other antigens. The two lots of the ETEC vaccine induced similar rates of serum antibody responses to CTB and CFA/I which were less frequent than the ASC responses to the same antigens. Based on these safety and immunogenicity data, an efficacy study of the ETEC vaccine is under way in the Israel Defense Force.", "We tested the efficacy of a killed oral vaccine for enterotoxigenic Escherichia coli (ETEC) diarrhoea to determine if two doses of vaccine with colonization factor antigens (CF) and cholera B subunit would protect against ETEC diarrhoea of travellers. Six hundred seventy-two healthy travellers going to Mexico or Guatemala were studied in a prospective, randomised, placebo-controlled trial. The primary outcome was a vaccine preventable outcome (VPO), defined as an episode of ETEC diarrhoea with an ETEC organism producing heat labile toxin (LT) or CF homologous with the vaccine, without other known causes. The vaccine was safe and stimulated anti-heat labile toxin antibodies. There was a significant decrease in more severe VPO episodes (PE=77%, p=0.039) as defined by symptoms that interfered with daily activities or more than five loose stools in a day, although the total number of VPO events did not differ significantly in the vaccine and placebo groups. We conclude that the new oral ETEC vaccine reduces the rate of more severe episodes of traveller's diarrhoea (TD) due to VPO-ETEC, but it did not reduce the overall rate of ETEC diarrhoea or of travellers' diarrhoea due to other causes.", "The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).", "Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing heat-labile enterotoxin (LT) from ETEC delivered to the skin by patch in travellers to Mexico and Guatemala.\n In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff. Primary endpoints were to investigate the field rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine efficacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37.5 mug of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or five), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659.\n Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22%) of 111 placebo recipients had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective efficacy [PE] 75%, p=0.0070) and severe diarrhoea (PE 84%, p=0.0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0.5 days vs 2.1 days, p=0.0006) with fewer loose stools (3.7 vs 10.5, p<0.0001) than placebo.\n Travellers' diarrhoea is a common ailment, with ETEC diarrhoea illness occurring in 10% of cases. The vaccine patch is safe and feasible, with benefits to the rate and severity of travellers' diarrhoea.", "Background: A prospective, randomized, double-blind, placebo-controlled trial of WC/rBS oral cholera vaccine was conducted in 502 U.S. college students attending summer educational programs in Mexico. Methods: Two doses of vaccine (or placebo) were administered 10 days apart immediately after arrival in Mexico. Results: The vaccine was free of significant adverse side effects. Anticholera toxin seroconversion was demonstrated in 86.7% of vaccinees compared to 8.2% of controls (p <.001). Postvaccination titers varied according to disease status (travelers' diarrhea) and enteropathogen isolated when disease developed. Protective efficacy (PE) against enterotoxigenic Escherichia coli (ETEC) diarrhea was 50% (95% CI, 14-71%), beginning 7 days after the second dose of WC/rBS. However, 74% of ETEC cases occurred within 7 days of the second dose, when no efficacy was demonstrated. Conclusions: Vaccines employed to prevent travelers' diarrhea will likely need to be administered before arrival in a developing country to be predictably beneficial. An unexpected finding was that infection with LT-ETEC after primary oral cholera immunization appears to augment the antitoxin response to WC/rBS vaccine. (J Travel Med 2:22-27, 1995)", "A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli (ETEC) vaccine containing six colonization factors (CFA/I, CS1, CS2, CS3, CS4, CS5) and 1mg of recombinant cholera toxin B subunit (the CF-BS-ETEC vaccine) was carried out in an urban slum of Dhaka city in Bangladesh. The study was carried out in a double blinded, placebo controlled design in 158 children, 18-36 months of age. Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12. The vaccine was well tolerated. The immune response was studied in 60 children (30 each in the placebo and vaccine group). Significant vaccine specific IgA antibody-secreting cell (ASC) responses were seen 7 days after ingestion of the first and second dose of the vaccine. The responses to CFA/I (P<or=0.001), CS2 (P=0.021), CS4 (P=0.009) and rCTB (P<or=0.001) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients (P=0.018 to <0.001). Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested (P=0.012 to <0.001) and IgG-ASCs to rCTB (P<0.001). Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose. The vaccine recipients also responded with IgA plasma antibodies to CFA/I, CS1, CS2, CS4 and rCTB after one or two doses of the vaccine (P=0.01 to <0.001). Subjects in the placebo group failed to mount responses to any of the antigens. The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I, CS2 and rCTB (61, 88 and 69% responder frequency, respectively) and the magnitude of the response was elevated in comparison to the pre-immune levels (P=0.031 to <0.001) and to the levels of the control group (P=0.003 to <0.001). This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children, 18-36 months of age and gives rise to significant systemic and mucosal IgA antibody responses.", "B-subunit/whole-cell cholera vaccine (BS-WC) has been shown to give Bangladeshi mothers and children only 3 months' protection against severe diarrhoea due to enterotoxigenic Escherichia coli (ETEC). Since a long-lasting effect is not necessary for protection against travellers' diarrhoea, a prospective double-blind study was conducted among tourists who went to Morocco from Finland. 307 tourists received two oral doses of BS-WC, whereas 308 controls received a placebo before departure. A research team went out with tourists and a laboratory for enteric pathogens was set up on location. A faecal specimen was taken from 100 randomly selected subjects before departure, from all travellers with diarrhoea, and routinely after return. Enteropathogenic bacteria were not isolated from any of the pre-departure specimens but were present during or after the holiday in 47% of tourists with travellers' diarrhoea, and in 14% of those without diarrhoea. BS-WC induced a 52% protection (p = 0.013) against diarrhoea caused by ETEC. The protection was better for mixed infections (65%, p = 0.016). The protective efficacy against a combination of ETEC and any other pathogen was 71% (p = 0.02), and that against ETEC plus Salmonella enterica even better at 82% (p = 0.01). Partial protection against travellers' diarrhoea is thus obtainable by active immunisation with BS-WC.", "Orally administered bovine immunoglobulins with specific activity against colonization factors of enterotoxigenic Escherichia coli (ETEC) could provide passive protection against ETEC challenge in volunteers. Twenty healthy adult volunteers ingested either a placebo or a partially enteric-coated preparation of bovine immunoglobulins with activity against the colonization factor antigens CFA/I, CS3, and CS6 and then were challenged with ETEC strain E24377A (CS1+, CS3+) administered with a standard meal. There was no difference in the incidence or severity of diarrhea among the 10 volunteers who received the bovine immunoglobulins and the 10 who received placebo. Either the specificity or titer of anti-colonization factor antibodies or the formulation of antibodies in this product was not adequate to provide passive protection against ETEC challenge.", "The immunogenicity of different preparations of an oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine was evaluated in Swedish volunteers previously unexposed to ETEC infection. The vaccine preparations consisted of recombinant cholera toxin B subunit (CTB) and various amounts of formalin-killed whole bacteria expressing the most prevalent colonization factor antigens (CFAs). Significant immunoglobulin A (IgA) antibody-secreting cell (ASC) responses against CTB and the various CFA components were seen in a majority of volunteers after two doses of ETEC vaccine independent of the vaccine lot given. The IgA ASC responses against CTB were significantly higher after the second than after the first immunization, whereas the CFA-specific IgA ASC responses were almost comparable after the first and second doses of ETEC vaccine. Two immunizations with one-third of a full dose of CFA-ETEC bacteria induced lower frequencies of IgA ASC responses against all the different CFAs than two full vaccine doses, i.e., 63 versus 80% for CFA/I, 56 versus 70% for CS1, 31 versus 65% for CS2, and 56 versus 75% for CS4. The proportion of vaccinees responding with rises in the titer of serum IgA antibody against the various CFA antigens was also lower after immunization with the reduced dose of CFA-ETEC bacteria. These findings suggest that measurements of circulating IgA ASCs can be used not only for qualitative but also for quantitative assessments of the immunogenicity of individual fimbrial antigens in various preparations of ETEC vaccine.", "Enterotoxigenic Escherichia coli (ETEC) is the most commonly isolated pathogen responsible for travelers' diarrhea and the cause of up to 650 million cases of pediatric diarrhea per year in the developing world. As a safe alternative to the prophylactic use of antibiotics, a hyperimmune bovine milk antibody product with specific activity against purified colonization factor antigens (CFAs) was developed and evaluated in a human challenge study. Twenty-five healthy adult volunteers were challenged orally with 10(9) cfu of a virulent CFA/I-bearing ETEC. In the randomized double-blind trial, 7 of 10 volunteers receiving a lactose-free placebo developed clinical diarrhea after challenge, compared with only 1 of 15 cases in volunteers receiving active product (Fisher's exact test, P < .0017). It is concluded that antibodies against CFAs alone are sufficient for protection and that prophylaxis with milk-derived immunoglobulin is a feasible alternative to existing drug interventions." ]

[ "11322745", "12153826", "16513860", "11379837", "12218423", "17450046", "18439112", "10761354" ]

[ "Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: a double-blind, placebo-controlled pilot trial.", "Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence.", "A randomized, double-blind, placebo-controlled study of risperidone maintenance treatment in children and adolescents with disruptive behavior disorders.", "A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities.", "Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs.", "Risperidone augmentation for treatment-resistant aggression in attention-deficit/hyperactivity disorder: a placebo-controlled pilot study.", "Randomized controlled pilot study of quetiapine in the treatment of adolescent conduct disorder.", "A double-blind pilot study of risperidone in the treatment of conduct disorder." ]

[ "Risperidone, an antipsychotic agent with combined serotonin (5-HT2A) and dopamine (D2) receptor-blocking properties, is associated with fewer extrapyramidal side effects in adults than conventional neuroleptics. Approved in 1993 for the treatment of schizophrenia, recent studies have highlighted its potential in other conditions, such as the management of behavioral disturbances. This phase II, double-blind, placebo-controlled study evaluated the efficacy and tolerability of risperidone in the treatment of persistent behavioral disturbances in children with borderline intellectual functioning. Thirteen patients (6-14 years) with low IQ (66-85) were enrolled in and completed the 4-week study. Risperidone, in daily doses of > or = 0.01 mg/kg (mean dose at treatment endpoint = 0.05 mg/kg; mean total dose = 1.2 mg/day), was significantly more effective than placebo in improving Aberrant Behavioral Checklist (ABC) symptom cluster scores for irritation (p < 0.05) and hyperactivity (p < 0.01), Clinical Global Impression score (p < 0.05), the Visual Analogue Scale score for individual target symptom (p < 0.001), and Personal Assessment Checklist scores for social relationships (p < 0.05) and occupational attitudes (p < 0.05). In addition, the improvement in total ABC score in the risperidone-treated group was clinically relevant (65% improvement vs. baseline), whereas the placebo-treated patients only improved 7% versus baseline. There was no difference between risperidone- and placebo-treated groups with respect to the occurrence of extrapyramidal side effects, and risperidone was well tolerated. In conclusion, short-term risperidone treatment was well tolerated and significantly more effective than placebo in controlling behavioral disturbances in children with low IQ.", "The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence.\n In this 6-week, multicenter, double-blind, parallel-group study of 118 children (aged 5-12 years) with severely disruptive behaviors and subaverage intelligence (IQ between 36 and 84, inclusive), the subjects received 0.02-0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form.\n The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint (change in score of -15.2 and -6.2, respectively). Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint, as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy/social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive/destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively.\n Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ.", "The authors compared the effects of maintenance versus withdrawal of risperidone treatment in children and adolescents with symptoms of disruptive behavior disorder.\n Patients with disruptive behavior disorder (5-17 years of age and a range of intellect) who had responded to risperidone treatment over 12 weeks were randomly assigned to 6 months of double-blind treatment with either risperidone or placebo. The primary efficacy measure was time to symptom recurrence, defined as sustained deterioration on either the Clinical Global Impression severity rating (/2 points) or the conduct problem subscale of the Nisonger Child Behavior Rating Form (/7 points). Secondary efficacy measures included rates of discontinuation due to symptom recurrence, disruptive behavior disorder symptoms, and general function. Safety and tolerability were also assessed. Risperidone dosage was based on weight (patients <50 kg: 0.25-0.75 mg/day; patients /50 kg: 0.5-1.5 mg/day).\n Treatment was initiated in 527 patients, with 335 randomly assigned to a double-blind maintenance condition. Time to symptom recurrence was significantly longer in patients who continued risperidone treatment than in those switched to placebo. Symptom recurrence in 25% of patients occurred after 119 days with risperidone and 37 days with placebo. Secondary efficacy measures also favored risperidone over placebo. Weight increased over the initial 12 weeks of treatment (mean weight z score change=0.2, SD=2.7, N=511), after which it plateaued.\n This study is the first placebo-controlled maintenance versus withdrawal trial of its kind in disruptive behavior disorder and provides evidence that patients who respond to initial treatment with risperidone would benefit from continuous treatment over the longer term.", "Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems. The present study was designed to examine the efficacy and safety of risperidone in a 6-week double-blind, randomized, parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence.\n We randomly assigned 38 adolescents (33 boys; 10 subjects with slightly subaverage IQ, 14 with borderline IQ, and 14 with mild mental retardation), who were hospitalized for treatment of psychiatric disorders associated with severe aggression, to receive risperidone or placebo. The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale (CGI-S), the modified Overt Aggression Scale (OAS-M), and the Aberrant Behavior Checklist (ABC). Side effects were measured using the Extrapyramidal Symptom Rating Scale (ESRS).\n The mean daily dose of risperidone at the end of treatment was 2.9 mg (range, 1.5-4 mg). Risperidone, compared with placebo, was associated with significant improvements on the CGI-S (p < .001) and the at-school ABC overall and hyperactivity scales (p < .05). During a 2-week washout following the 6-week trial, a statistically significant worsening was found in the risperidone group on the CGI-S scale, the OAS-M. and the ABC. Extrapyramidal symptoms were absent or very mild during risperidone treatment. Transient tiredness was present in 11 (58%) of 19 drug-treated subjects. Other untoward effects included sialorrhea, nausea, and slight weight gain (mean = 3.5% of body weight in the risperidone group). No clinically relevant changes were found in laboratory parameters, electrocardiogram, heart rate, or blood pressure.\n These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence, and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general.", "To determine whether risperidone is effective in reducing symptoms of disruptive behaviors (such as aggression, impulsivity, defiance of authority figures, and property destruction) associated with conduct disorder, oppositional defiant disorder, and disruptive behavior disorder-not otherwise specified in children with subaverage IQs.\n The trial consisted of a 1-week, single-blind, placebo run-in period and was followed by a 6-week, double-blind, placebo-controlled period. One hundred ten children (aged 5-12 years inclusive) with an IQ of 36-84 with a disruptive behavior disorder and a score of at least 24 on the Conduct Problem subscale of the Nisonger Child Behavior Rating Form (NCBRF) were enrolled. Eighty percent of subjects had comorbid attention-deficit/hyperactivity disorder (ADHD). Risperidone doses ranged from 0.02 to 0.06 mg/kg per day. Subjects were rated on the NCBRF, Aberrant Behavior Checklist, Behavior Problems Inventory, Clinical Global Impressions (CGI), modified California Verbal Learning Test (CVLT), and a continuous performance task (CPT).\n The intention-to-treat analysis of risperidone-treated subjects showed a significant (p < .001) reduction in mean scores (from 33.4 at baseline to 17.6 at end point; 47.3% reduction) versus placebo-treated subjects (mean baseline of 32.6 to 25.8 at end point; 20.9% reduction) on the Conduct Problem subscale of the NCBRF. Between-group differences in favor of risperidone were seen as early as week 1 and were significant at all post-baseline visits. Other subscales showed significant improvement with risperidone compared with placebo. CGI scale ratings of improvement showed highly significant gains for risperidone over placebo. A subanalysis demonstrated that the effect of risperidone was unaffected by diagnosis, presence/absence of ADHD, psychostimulant use, IQ status, and somnolence. Risperidone produced no changes on the cognitive variables (CPT/modified CVLT). The most common side effects included somnolence, headache, appetite increase, and dyspepsia. Side effects related to extrapyramidal symptoms were reported in 7 (13.2%) and 3 (5.3%) of the subjects in the risperidone and placebo groups, respectively (p = .245).\n Risperidone appears to be an adequately tolerated and effective treatment in children with subaverage IQs and severe disruptive behaviors such as aggression and destructive behavior.", "To evaluate the effects of risperidone augmentation for treatment-resistant aggression in children with attention-deficit/hyperactivity disorder (ADHD).\n Twenty-five children (ages 7-12 years) with attention-deficit/hyperactivity disorder (ADHD) and significant aggressive behaviors were randomized to risperidone or placebo for 4 weeks for this double-blind study. Subjects were already in treatment with a constant dose of psychostimulant medication. The primary efficacy measure was change from baseline in the Children's Aggression Scale-Parent (CAS-P) and -Teacher (CAS-T) total scores.\n The mean risperidone dose at endpoint was 1.08 mg/day. For the CAS-P total score, a significant difference was found (chi(1)(2) = 4.30, p < .05) with 100% of risperidone subjects improving by more than 30% from baseline to endpoint, whereas only 77% of the placebo group reported a similar response. No differences were found on the CAS-T total score. For the CAS-P and CAS-T, no significant interaction was found between treatment group and time. Rates of adverse events did not differ significantly between groups.\n Risperidone treatment appears to be well tolerated and modestly effective when used in combination with psychostimulants for treatment-resistant aggression in children with ADHD.", "The aim of this study was to examine whether quetiapine is superior to placebo in the treatment of adolescents with conduct disorder.\n This was a 7-week, randomized, double-blind, placebo-controlled pilot study with two parallel arms. Nine youths were randomly assigned to receive quetiapine, and 10 youths were randomly assigned to receive placebo. Patients were assessed weekly throughout the trial. Quetiapine was dosed twice daily, and medications could be titrated flexibly through the end of study week 5. The dose was fixed for the final 2 weeks of the study. The primary outcome measures were the clinician-assessed Clinical Global Impressions-Severity (CGI-S) and-Improvement (CGI-I) scales. Secondary outcome measures included parent-assessed quality of life, the overt aggression scale (OAS), and the conduct problems subscale of the Conners' Parent Rating Scale (CPRS-CP).\n The final mean dose of quetiapine was 294 +/- 78 mg/day (range 200-600 mg/day). Quetiapine was superior to placebo on all clinician-assessed measures and on the parent-assessed quality of life rating scale. No differences were found on the parent-completed OAS and CPRS-CP. Quetiapine was well tolerated. One patient randomized to quetiapine developed akathisia, requiring medication discontinuation. No other extrapyramidal side effects occurred in patients receiving active drug.\n This methodologically controlled pilot study provides data that quetiapine may have efficacy in the treatment of adolescents with conduct disorder. Because of the preliminary nature of the study, further research with larger samples is needed to confirm these findings.", "To examine whether risperidone is superior to placebo in the treatment of youths with conduct disorder.\n This was a 10-week, randomized, double-blind, placebo-controlled study with 2 parallel arms. Ten youths were randomly assigned to receive placebo and 10 youths were randomly assigned to receive risperidone. Patients were seen weekly throughout the trial. Medications could be increased at weekly intervals during the first 6 weeks of the study from an initial dose of 0.25 mg or 0.50 mg each morning, depending on patient weight. Patients weighing less than 50 kg had a maximum total daily dose of risperidone of 1.5 mg. Patients weighing 50 kg or greater had a maximum total daily dose of risperidone of 3.0 mg. The primary outcome measure was the Rating of Aggression Against People and/or Property Scale.\n Risperidone was superior to placebo in ameliorating aggression on most measures. Risperidone was reasonably well tolerated, with none of the risperidone-treated patients developing extrapyramidal side effects.\n These data provide preliminary evidence that risperidone may have efficacy in the treatment of youths with conduct disorder. Because of the small sample size and the brief length of this study, further research is necessary to confirm these findings." ]

[ "2809781", "1403397", "1642342", "1993963", "17398307", "17705879", "8874303", "2958819", "8905428", "9104623" ]

[ "Routine use of dexamethasone for the prevention of postextubation respiratory distress.", "Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema.", "Evaluation of risk factors for laryngeal edema after tracheal extubation in adults and its prevention by dexamethasone. A placebo-controlled, double-blind, multicenter study.", "Dexamethasone in the prevention of postextubation stridor in children.", "12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial.", "Corticosteroids to prevent postextubation upper airway obstruction: the evidence mounts.", "Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial.", "[Laryngeal edema after extubation. Do corticosteroids play a role in its prevention?].", "Postextubation laryngeal edema in adults. Risk factor evaluation and prevention by hydrocortisone.", "Extubation failure due to post-extubation stridor is better correlated with neurologic impairment than with upper airway lesions in critically ill pediatric patients." ]

[ "We evaluated the routine use of dexamethasone for the prevention of postextubation respiratory distress by entering 60 ventilated infants into a prospective, randomized, blinded study. Thirty minutes before extubation, 30 infants were given a single dose of intravenous dexamethasone (0.25 mg/kg), and 30 infants received saline placebo. Infants were intubated orotracheally for at least 48 hours following a single intubation and were maintained on low ventilator settings (F10(2) less than 0.35, intermittent mandatory ventilation [IMV] less than 6, positive end-expiratory pressure [PEEP] less than 4) at least 12 hours before extubation. Following extubation, all infants weighing less than 1500 g were routinely placed on nasal continuous positive airway pressure (NCPAP). There was no difference between the two groups in postextubation Downes' score, serum pH, PCO2, or oxygen requirement at 30 minutes, 6 hours, and 24 hours. Respiratory acidosis occurred in one steroid-treated patient and in two placebo-treated infants. Stridor occurred in four infants in each group. No infant developed postextubation lobar atelectasis or required reintubation. We conclude that prophylactic administration of dexamethasone does not improve the immediate postextubation course of infants following a single intubation and that its routine use at the time of extubation is not indicated.", "We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants.", "Because laryngeal edema (LE) after tracheal extubation is likely to result from an exudative response, corticosteroids often are given routinely as a preventive treatment. No adequate controlled study supports this strategy, however. A prospective, randomized, placebo-controlled, double-blind, multicenter trial that included 700 consecutive patients requiring tracheal intubation and mechanical ventilation was conducted to determine risk factors for LE occurrence after tracheal extubation in adults and to evaluate the efficacy of corticosteroids in its prevention. One hour before extubation, patients were given either an intravenous bolus of 8 mg dexamethasone or a placebo. Patients were divided into two groups: 1) those in whom short-duration intubation (SDI, less than 36 h) was administered; and 2) those in whom long-duration intubation (LDI, more than 36 h) was administered. Minor LE was diagnosed when either stridor or laryngeal dyspnea, or both, occurred; major LE was diagnosed when reintubation due to LE was required, with LE evidenced during direct laryngoscopy. The overall incidence of LE was 4.2% and varied among the six participating centers from 2.3 to 6.9% (not significant). In only seven patients (1%), all with LDI, was tracheal reintubation required for LE. Laryngeal edema occurred more frequently after LDI than after SDI (7.2 vs. 0.9%; P less than 0.001). It also was more frequent in female than in male patients (20/284 vs. 8/379; P less than 0.05), irrespective of intubation duration and treatment. There was no association between LE and either difficulty/route of intubation or admission diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children, we conducted a prospective, randomized, double-blind trial of dexamethasone versus saline solution. The patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor: age, duration of intubation, upper airway trauma, circulatory compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting. There was no statistical difference in incidence of postextubation stridor in the two groups; 23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy (p = 0.21). We conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted.", "The efficacy of corticosteroids in reducing the incidence of postextubation laryngeal oedema is controversial. We aimed to test our hypothesis that methylprednisolone started 12 h before a planned extubation could prevent postextubation laryngeal oedema.\n We did a placebo-controlled, double-blind multicentre trial in 761 adults in intensive-care units. Patients who were ventilated for more than 36 h and underwent a planned extubation received intravenous 20 mg methylprednisolone (n=380) or placebo (381) 12 h before extubation and every 4 h until tube removal. The primary endpoint was occurrence of laryngeal oedema within 24 h of extubation. Laryngeal oedema was clinically diagnosed and deemed serious if tracheal reintubation was needed. Analyses were done on a per protocol and intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00199576.\n 63 patients could not be assessed, mainly because of self-extubation (n=16) or cancelled extubation (44) between randomisation and planned extubation. 698 patients were analysed (343 in placebo group, 355 in methylprednisolone group). Methylprednisolone significantly reduced the incidence of postextubation laryngeal oedema (11 of 355, 3%vs 76 of 343, 22%, p<0.0001), the global incidence of reintubations (13 of 355, 4%vs 26 of 343, 8%, p=0.02), and the proportion of reintubations secondary to laryngeal oedema (one of 13, 8 %vs 14 of 26, 54%, p=0.005). One patient in each group died after extubation, and atelectasia occurred in one patient given methylprednisolone.\n Methylprednisolone started 12 h before a planned extubation substantially reduced the incidence of postextubation laryngeal oedema and reintubation. Such pretreatment should be considered in adult patients before a planned extubation that follows a tracheal intubation of more than 36 h.", "Intubation of the airway can lead to laryngotracheal injury, resulting in extubation failure from upper airway obstruction (UAO). A number of factors can help to identify patients who are at greatest risk for postextubation UAO. Three randomized controlled trials demonstrate that prophylactic corticosteroids decrease the risk for postextubation UAO and probably the need for re-intubation.", "To determine whether dexamethasone prevents postextubation airway obstruction in young children.\n Prospective, randomized, double-blind, placebo-controlled study.\n Pediatric intensive care unit of a university teaching hospital.\n Sixty-six children, < 5 yrs of age, intubated and mechanically ventilated for > 48 hrs.\n Patients were randomized to receive intravenous dexamethasone (0.5 mg/kg, maximum dose 10 mg) or saline, every 6 hrs for six doses, beginning 6 to 12 hrs before elective extubation.\n Dependent variables included the presence of stridor, Croup Score, and pulsus paradoxus at 10 mins, 6, 12, and 24 hrs after extubation; need for aerosolized racemic epinephrine and reintubation. The dexamethasone and placebo groups were similar in age (median 3 months [range 1 to 57] vs. 4 months [range 1 to 59], p = .6), frequency of underlying airway anomalies (3/33 vs. 3/33, p = 1.0), and duration of mechanical ventilation (median 3.3 days [range 2.1 to 39] vs. 3.5 days [range 2.1 to 15], p = .7). The dexamethasone group had a lower frequency of stridor, Croup Score, and pulsus paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation. Fewer dexamethasone-treated patients required epinephrine aerosol (4/31 vs. 22/32, p < .0001) and reintubation (0/31 vs. 7/32, p < .01). Three patients exited the study early-one patient in the dexamethasone group had occult gastrointestinal hemorrhage and one patient in each group had hypertension.\n Pretreatment with dexamethasone decreases the frequency of postextubation airway obstruction in children.", "The role of corticosteroids in the prevention of post-extubation laryngeal oedema was evaluated in a randomized study of 276 patients under mechanical ventilation. Fifty per cent of the patients received methylprednisolone 40 mg intramuscularly and intravenously. The nasotracheal tubes used had a large volume, low-pressure balloon. Laryngeal oedema, confirmed by laryngoscopy, occurred in six patients (2%), 4 of whom were in the corticosteroid-treated group, and required immediate reintubation in 4 cases. Thus, the incidence of laryngeal oedema was not modified by corticosteroids. Regular prescription of corticosteroids does not seem to be useful before extubation of patients intubated with large volume, low-pressure balloon tubes.", "To evaluate the risk factors for postextubation laryngeal stridor and its prevention by hydrocortisone in adult patients.\n Prospective, randomized, double-blind, placebo controlled study.\n Medical and surgical ICU of a tertiary teaching hospital.\n 77 consecutive patients of both sexes, who had undergone tracheal intubation for more than 24 h and fulfilled the weaning criteria, were eligible for the study. Patients were excluded if they were less than 15 years of age, had a disease or the surgery of the throat, or had been extubated during the current hospitalization.\n The control group received placebo (normal saline 3 cc) and the experimental group received hydrocortisone 100 mg by intravenous infusion 60 min before extubation.\n Patients were observed 24 h after extubation for symptoms or signs of laryngeal edema or stridor: prolonged inspiration with accessory usage of respiratory muscles or crowing sound with inspiration or reintubation.\n The overall incidence of postextubation stridor was 22% (17/77). Only one patient (1%), who belonged to the control group, needed reintubation. 39% of female patients and 17% of male patients developed stridor. The relative risk of females developing this complication was 2.29. 7/39 of the hydrocortisone group and 10/38 of patients in the control group developed postextubation stridor.\n Hydrocortisone did not significantly reduce the incidence of postextubation laryngeal edema or stridor. From the risk factors evaluated, we were unable to demonstrate a statistical correlation between postextubation stidor and the duration of the intubation, the patient's age, the internal diameter of the endotracheal tube, or the route of intubation. However, female patients were more likely to develop this complication.", "The incidence of post-extubation stridor (PES) in a pediatric intensive care unit (PICU) and the need for reintubation is not known. Predictors of success on a subsequent extubation attempt and the efficacy of dexamethasone treatment prior to a subsequent extubation attempt are not established. In a prospective randomized double blind-controlled study in two PICU's in a university children's hospital setting, of 5,566 admissions over 35-months, we identified 32 patients who failed primary extubation and were reintubated for PES. Twenty-six patients were enrolled in the study and three subsequently excluded. Twelve were randomized to receive dexamethasone and 11 received sodium chloride placebo. Fifteen patients succeeded study extubation and eight failed. Of those receiving dexamethasone, nine patients succeeded and three failed. Of those receiving placebo, six patients succeeded and five failed. There was a poor correlation between anatomical abnormalities of the airway and failure of study extubation. Extubation failure was better correlated with neurologic impairment in the patients. We present a stridor score and demonstrate that it is an excellent predictor of success versus failure for the study extubation. Dexamethasone pre-treatment did not reduce stridor score. We are unable to conclude if dexamethasone pre-treatment reduces extubation failure. We speculate that neurologic impairment leads to extubation failure in critically ill pediatric patients." ]

[ "10621863", "7513332", "8851371", "2361097", "7521612" ]

[ "Pitfalls in placebo-controlled trials in palliative care: dexamethasone for the palliation of malignant bowel obstruction.", "Symptom control in terminally ill patients with malignant bowel obstruction (MBO).", "Chronic nausea in advanced cancer patients: a retrospective assessment of a metoclopramide-based antiemetic regimen.", "The use of corticosteroids for symptom management in terminally ill patients.", "Administration of drugs by infusion pumps in palliative medicine." ]

[ "To determine the effect of dexamethasone when treating malignant bowel obstruction, 35 patients were randomized to receive intravenous dexamethasone or a placebo, crossing over to the alternate treatment arm if there had been no resolution of obstruction by day 5. This was done in two consecutive studies. Patients were stratified according to whether or not they had received specific anticancer therapy within 28 days of study. In trial 1, 15 out of 22 patients 'responded' (resolution of obstruction by day 5; 10 on dexamethasone, five on placebo). Eleven out of 15 patients were 'on treatment'. In trial 2, six out of 13 responded (three on dexamethasone, three on placebo); three out of six were 'on treatment'. When both studies are combined, 60% (21/35) patients responded (13 on dexamethasone, eight on placebo). Poor patient accrual terminated both studies. Numbers are too small to allow a combination of studies or formal statistical analysis. We are unable to make any conclusion as to the effectiveness of dexamethasone in the palliation of malignant bowel disease.", "The inadequacy of prolonged conservative management with nasogastric suction and intravenous fluids for terminally ill patients with bowel obstruction has long been recognized. Using previous reports and our experience on the Palliative Care Unit at the Edmonton General Hospital, we have developed a basic approach to bowel obstruction management. In a review of 100 consecutive patients who died on our Palliative Care Unit, 15 required medical management for bowel obstruction. Evaluation of these cases suggests that intensive medical management can provide good symptom control without using intravenous lines and with minimal use of nasogastric tubes.", "The purpose of this retrospective study is to assess the frequency and intensity of chronic nausea in patients admitted to the Palliative Care Unit and the results of a metoclopramide-based treatment regimen. We reviewed the medical records of 100 consecutive patients admitted to the Palliative Care Unit at the Edmonton General Hospital until death during 1992-1993. All patients had terminal cancer and normal cognitive function. All patients completed the Functional Analogue Scale for appetite, nausea, pain, activity, shortness of breath, and sensation of well-being at 1000 and 1600 hours every day. Patients who complained of nausea initially received metoclopramide 10 mg every 4 hr orally or subcutaneously (Step 1). If nausea persisted, dexamethasone 10 mg twice daily was added (Step 2). Step 3 consisted of a continuous subcutaneous infusion of metoclopramide of 60-120 mg/day plus dexamethasone. If no response was observed, other antiemetics were administered (Step 4). Upon admission to the unit, 32 patients (32%) presented with nausea. During the average admission of 25 +/- 13 days, 98 patients (98%) developed nausea. Twenty-five patients (25%) required other antiemetics because of bowel obstruction (18), extrapyramidal side effects (3), or other reasons (4). Most patients without bowel obstruction achieved excellent control of nausea using the metoclopramide-based regimen. During the first 5 days and last 5 days of admission, nausea had significantly lower intensity than the rest of the symptoms that were monitored. Our results suggest that, although nausea is very frequent, it can be well controlled in the majority of patients using safe and simple antiemetic regimens.", "nan", "A retrospective study was carried out in 100 adult patients with advanced malignant disease. They were given subcutaneous continuous infusions of medication for symptom relief. The drugs were administered through a butterfly needle inserted subcutaneously in the anterior chest wall using a battery-operated infusion pump. The indications for using this technique were inability to swallow due to deteriorating general condition, oesophageal obstruction, intestinal obstruction, severe nausea and vomiting, terminal dyspnoea and poor pain control with oral opiates. All patients received morphine; other drugs administered through the syringe driver included hyoscine, metoclopramide, cyclizine, dexamethasone and midazolam. Ninety-four patients continued subcutaneous infusion until death. The mean duration of treatment was 9.1 days. The treatment was well tolerated by the patients and controlled their symptoms satisfactorily in the great majority. The use of continuous subcutaneous infusion via a syringe driver gives good symptom control. In the last days of life when the patients have difficulty tolerating oral medication, continuous subcutaneous infusion is a superior alternative to frequent intermittent parenteral injections." ]

[ "22050864", "12524098", "12057748", "12093851", "12042269", "10966992", "16540614", "16055454", "14507836", "12930586", "14967390", "11779600", "9886530" ]

[ "Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial.", "Blastocyst transfer decreases multiple pregnancy rates in in vitro fertilization cycles: a randomized controlled trial.", "A prospective randomized study comparing day 3 with blastocyst-stage embryo transfer.", "Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer.", "A prospective randomized study: day 2 versus day 5 embryo transfer.", "Day 5 versus day 3 embryo transfer: a controlled randomized trial.", "In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos.", "Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study.", "Similar delivery rates in a selected group of patients, for day 2 and day 5 embryos both cultured in sequential medium: a randomized study.", "Day 3 versus day 5 embryo transfer: a prospective randomized study.", "Comparison of embryo transfer on day 2, day 3, and day 6: a prospective randomized study.", "Blastocyst culture and transfer: a step toward improved in vitro fertilization outcome.", "A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization." ]

[ "This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52–0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46–0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day\n Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.", "nan", "nan", "The respective advantages of day 3 and day 5 embryo transfer are a matter of debate. Previous comparisons did not include pronuclear stage zygote scoring and cumulative success rates (fresh and cryopreserved embryos).\n Patients were randomized prospectively for day 3 or day 5 embryo transfer. Day 3 embryos were selected for transfer and cryopreservation by using combined evaluation at the pronuclear and cleavage stages.\n There was no difference between day 3 and day 5 fresh embryo transfers as to the rates of pregnancy (58 versus 62%), clinical pregnancy (56 versus 58%), delivery (50 versus 48%), implantation (35 versus 38%) and birth (33 versus 36%) rates. The corresponding values for cryopreserved embryo transfers were also similar. However, day 3 embryo transfer compared favourably with day 5 transfer when the pregnancy (90 versus 66%), clinical pregnancy (85 versus 62%) and delivery (77 versus 52%) rates were calculated per oocyte recovery attempt.\n With a selected population of good prognosis patients and our embryo selection criteria, the implantation potential of day 3 and day 5 embryos is equal. Per oocyte recovery attempt, day 3 transfer is more clinically efficient than day 5 transfer, but at least one transfer of cryopreserved embryos is necessary to manifest this superiority.", "This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers.\n Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred.\n The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%).\n This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.", "Blastocyst transfer has been suggested to improve implantation rate without affecting pregnancy rate. The aim of this study was to compare the pregnancy and implantation rates of day 3 and 5 transfers in a prospective randomized manner. Patients with four or more zygotes were randomly allocated on day 1 to either day 3 or 5 transfers. Fertilization was achieved through regular IVF or intracytoplasmic sperm injection. Zygotes were kept in Medicult IVF medium for day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively for day 5 transfers. The morphologically best two or three embryos or blastocysts were chosen for transfer in both groups. Overall pregnancy rates per embryo transfer were the same (39%) in day 3 and 5 transfers. Implantation rates were 21 and 24% for day 3 and 5 transfers respectively. The pregnancy and implantation rates for day 5 transfers were significantly affected by the availability of at least one blastocyst to transfer and the number of zygotes. The number of good quality embryos on day 3 also significantly affected pregnancy and implantation rates on day 5 transfers. Multiple gestation rate, number of abortions and ongoing pregnancies were similar in both groups. In conclusion, day 3 and 5 transfer had similar pregnancy, implantation and twinning rates. Currently, day 5 transfers have no advantages over day 3 transfers.", "Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age. We designed a prospective, randomized, controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage (day 3) embryo and those undergoing transfer of a single blastocyst-stage (day 5) embryo.\n We studied 351 infertile women under 36 years of age who were randomly assigned to undergo transfer of either a single cleavage-stage embryo (176 patients) or a single blastocyst-stage embryo (175 patients). Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone.\n The study was terminated early after a prespecified interim analysis (which included 50 percent of the planned number of patients) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo (P=0.02). The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo (32.0 percent vs. 21.6 percent; relative risk, 1.48; 95 percent confidence interval, 1.04 to 2.11). Two multiple births occurred, both of monozygotic twins, both of which were in the group undergoing transfer of a single cleavage-stage embryo.\n These findings support the transfer of a single blastocyst-stage (day 5) embryo in infertile women under 36 years of age.\n Copyright 2006 Massachusetts Medical Society.", "In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3.\n Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group.\n Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05).\n A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.", "The existence of a real benefit of blastocyst transfer is still a matter of debate. The aim of this study was to compare, in a prospective randomized trial, the outcome of day 2 and day 5 transfer of human embryos cultured in an 'in-house' sequential medium.\n A total of 193 cycles from 171 patients with less than four previous IVF cycles, <39 years old and with four or more zygotes on day 1, were randomly allocated to day 2 (94 cycles) or day 5 (99 cycles) transfer. Zygotes were kept in fertilization medium until 18 h post-fertilization and then placed in a 'glucose-free' cleavage medium. Embryos allocated for day 5 transfer were placed in a blastocyst medium 66 h post-fertilization. Two or three embryos were replaced according to the morphology.\n A mean (+/- SEM) number of 2.1 +/- 0.4 and 1.9 +/- 0.3 embryos were replaced on day 2 and day 5 (P < 0.001) respectively. Delivery rates per transfer were 44.1 and 37.1% [P = not significant (NS)], implantation rates were 31.4 and 29.4% (NS) and multiple delivery rates 22 and 36% (NS) for day 2 and day 5 groups respectively. Ten patients (10.1%) had no blastocysts available for transfer.\n No clear benefits were observed using blastocyst transfer for patients aged <39 years who had had less than four previous IVF cycle attempts.", "Transfer of embryos at the blastocyst stage has been associated with exceptionally high implantation rates. There are, however, only a few prospective randomized studies comparing day 3 versus day 5 embryo transfer. Furthermore, the number of embryos replaced in the day 3 group transfer is often higher than the number of blastocysts replaced, thereby affecting implantation rates. A total of 118 patients undergoing standard IVF/intracytoplasmic sperm injection who had developed at least three 8-cell embryos showing <20% extracellular fragmentation on day 3 were randomized for day 3 or day 5 transfer. A maximum of two embryos were replaced. In this prospective, randomized study the implantation and pregnancy potential of embryos transferred on day 3 or day 5 were compared. Equal numbers of embryos were replaced in the two groups. There was no statistically significant difference between day 3 and day 5 transfer regarding positive human chorionic gonadotrophin rates (70 versus 67%), clinical pregnancy rates (61 versus 51%), implantation rates (44 versus 37%), twinning rates (42 versus 41%) and rates of early pregnancy loss (15 versus 29%). Transfer of embryos on day 3 or 5 showed similar implantation rates when equal numbers of embryos were transferred. Embryo transfer at the blastocyst stage seems to have no advantage over day 3 transfer in patients with more than two 8-cell embryos showing less than 20% fragmentation on day 3.", "A prospective randomized study of 243 embryo transfers revealed that the use of blastocysts in assisted reproductive technology is not more effective than the use of day 2 and day 3 embryos.", "To evaluate the efficacy of blastocyst culture and transfer in human in vitro fertilization (IVF) as compared to day 3 embryo transfer.\n Prospective randomized trial.\n Private assisted reproduction unit.\n A total of 162 IVF patients were included in the day 3 embryo transfer (n = 82) and blastocyst transfer (n = 80) groups.\n Embryo transfer on day 3 after culture in the standard culture media and blastocyst transfer on day 5 or 6 after culture in the sequential culture media.\n Implantation and pregnancy rates, multiple gestation rate.\n The implantation rate for embryos transferred at the blastocyst stage was significantly higher than that for embryos transferred on day 3 (26% vs. 13%). The viable pregnancy rate was similar in both groups (29% vs. 26%). Significantly fewer embryos were required for transfer at the blastocyst stage compared with day 3 embryo transfer (2.0 +/- 0.1 vs. 3.5 +/- 0.63). The high-order multiple gestation rate was significantly less with the blastocyst transfer than with the day 3 embryo transfer (4% vs. 19%).\n With the use of blastocyst culture, a few embryos can be transferred without decreasing the overall pregnancy rate. This may reduce multiple gestations and improve human IVF outcome.", "The effectiveness of blastocyst culture and transfer in human in-vitro fertilization (IVF) was evaluated in a prospective randomized trial in patients having a moderate to good response to gonadotrophin stimulation. Embryos were transferred either on day 3 after culture to around the 8-cell stage in Ham's F-10 medium supplemented with fetal cord serum, or on day 5 after culture to the blastocyst stage in the sequential serum-free media G 1.2 and G 2.2. The pregnancy rates after transfer on day 3 or day 5 were equivalent, 66 and 71% respectively; however, significantly more embryos were transferred on day 3 (3.7) than on day 5 (2.2). The number of blastocysts transferred did not affect the implantation rate, and pregnancy rates when either two or three blastocysts were transferred were 68 and 87% respectively. The implantation rate of the blastocysts (50.5% fetal heart beat) was significantly higher compared to the cleavage stage embryos transferred on day 3 (30.1%). The percentage of blastocyst development was not affected by the number of 2-pronuclear embryos, or by maternal age. Irrespective of the number of blastocysts formed, pregnancy rates were similar. Furthermore, the pregnancy rate following blastocyst transfer in patients with 10 or more follicles at the time of human chorionic gonadotrophin administration was not affected by patient age. More than 60% of patients having blastocyst culture and transfer had supernumerary embryos for cryopreservation. The establishment of a pregnancy following thaw and transfer confirmed the viability of cryopreserved blastocysts cultured in the absence of serum or co-culture. The ability to transfer just two blastocysts while maintaining high pregnancy rates will therefore help to eliminate high order multiple gestations and improve the overall efficiency of human IVF." ]

[ "19745648", "15969244", "2841818", "19609225", "16782922", "20220537", "15863547", "17565936", "17179056", "16645532", "17587516", "11352967", "16039414" ]

[ "Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black cohosh) in women with anxiety disorder due to menopause.", "Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol.", "[Clinical and endocrinologic studies of the treatment of ovarian insufficiency manifestations following hysterectomy with intact adnexa].", "Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial.", "Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1.", "Effect of exercise and Cimicifuga racemosa (CR BNO 1055) on bone mineral density, 10-year coronary heart disease risk, and menopausal complaints: the randomized controlled Training and Cimicifuga racemosa Erlangen (TRACE) study.", "Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms.", "Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial.", "Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.", "Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study.", "Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone.", "Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer.", "Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial." ]

[ "We conducted a randomized, double-blind, placebo-controlled, parallel group trial of the efficacy and tolerability of Cimicifuga racemosa (black cohosh) extract for the treatment of anxiety disorder due to menopause. We hypothesized that black cohosh would be superior to placebo in reducing anxiety symptoms of menopause, with a comparable tolerability profile to placebo.\n Subjects were randomized to therapy with either pharmaceutical-grade black cohosh extract (n = 15) or placebo (n = 13) for up to 12 weeks. The primary outcome measure was changed over time in total Hamilton Anxiety Rating Scale (HAM-A) scores. Secondary outcomes included a change in scores on the Beck Anxiety Inventory, Green Climacteric Scale (GCS), and Psychological General Well-Being Index (PGWBI) and the proportion of patients with a change of 50% or higher in baseline HAM-A scores.\n There was neither a significant group difference in change over time in total HAM-A scores (P = 0.294) nor a group difference in the proportion of subjects with a reduction of 50% or higher in baseline HAM-A scores at study end point (P = 0.79). There was a significantly greater reduction in the total GCS scores during placebo (vs black cohosh; P = 0.035) but no group difference in change over time in the GCS subscale scores or in the PGWBI (P = 0.140). One subject (3.6%) taking black cohosh discontinued treatment because of adverse events.\n We found no statistically significant anxiolytic effect of black cohosh (vs placebo). However, small sample size, choice of black cohosh preparation, and dosage used may have been limiting factors producing negative results.", "To investigate, in a randomized clinical study, the efficacy of an isopropanolic aqueous extract of Cimicifuga racemosa (CR) on climacteric complaints in comparison with low-dose transdermal estradiol (TTSE2). Hormonal parameters, lipid profile and endometrial thickness were also evaluated.\n Sixty-four postmenopausal women were enrolled and over the course of 3 months filled in a diary recording the number of hot flushes per day. Other climacteric symptoms (vasomotor and urogenital symptoms) as well as anxiety and depression, were evaluated at baseline and after 3 months. Gonadotropins (follicle-stimulating hormone (FSH), luetinizing hormone (LH)), prolactin (PRL), 17 beta-estradiol (17beta-E2) and cortisol, lipid profile (total cholesterol high-density lipoprotein (HDL)/low-density lipoprotein (LDL)-cholesterol, triglycerides, liver function (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase) and endometrial thickness were measured. Patients were randomly allocated to receive, for 3 months, either 40 mg isopropanolic aqueous CR extract daily or 25 microg TTSE2 every 7 days plus dihydrogesterone 10 mg/day for the last 12 days of the 3-month estradiol treatment.\n Both CR and low-dose TTSE2 significantly reduced the number of hot flushes per day (p < 0.001) and vasomotor symptoms (p < 0.001), starting at the first month of treatment. Such a positive effect was maintained throughout the 3 months of observation, without any significant difference between the two treatments. An identical effect was evident also for both anxiety (p < 0.001) and depression (p < 0.001) which were significantly reduced following 3 months of both CR and low-dose TTSE2. Total cholesterol was unchanged by CR treatment but significantly (p < 0.033) reduced by 3 months of low-dose TTSE2. A slight but significant increase of HDL-cholesterol (p < 0.04) was found only in women treated with CR, while LDL-cholesterol levels were significantly lowered by 3 months of both CR (p < 0.003) and low dose TTSE2 (p < 0.002). Triglycerides were not affected by both treatments, nor was liver function. FSH, LH and cortisol were not significantly affected after the 3-month treatment, while PRL (p < 0.005) and 17 beta-E2 (p < 0.001) were increased slightly only by low-dose TTSE2. Endometrial thickness was not affected by either CR or low-dose TTSE2.\n CR (40 mg/day) may be a valid alternative to low-dose TTSE2 in the management of climacteric complaints in those women who cannot be treated with or just refuse conventional strategies.", "60 hysterectomized patients under 40 years old, who all had at least one intact ovary and still complained of climacteric symptoms, were treated with estriol, conjugated estrogens, estrogen-gestagen sequential therapy or an extract from cimicifuga racemosa after randomized distribution into 4 equal groups. Therapy was controlled after 4, 8, 12 and 24 weeks with a modified Kupperman-Index that also included trophic disorders of the genitals, and also by serum-FSH and -LH measurement. In all groups, the modified Kupperman-Index became significantly lower, the parallel decrease of gonadotropins could not be confirmed statistically, however. There were no significant differences between groups concerning therapy success.", "The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of menopausal vasomotor symptoms.\n This study was a randomized, four-arm, double-blind clinical trial of standardized black cohosh, red clover, placebo, and 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA; n = 89). Primary outcome measures were reduction in vasomotor symptoms (hot flashes and night sweats) by black cohosh and red clover compared with placebo; secondary outcomes included safety evaluation, reduction of somatic symptoms, relief of sexual dysfunction, and overall improvement in quality of life.\n Reductions in number of vasomotor symptoms after a 12-month intervention were as follows: black cohosh (34%), red clover (57%), placebo (63%), and CEE/MPA (94%), with only CEE/MPA differing significantly from placebo. Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo. Secondary measures indicated that both botanicals were safe as administered. In general, there were no improvements in other menopausal symptoms.\n Compared with placebo, black cohosh and red clover did not reduce the number of vasomotor symptoms. Safety monitoring indicated that chemically and biologically standardized extracts of black cohosh and red clover were safe during daily administration for 12 months.", "Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal.\n A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period.\n Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment.\n This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.", "The aim of this study was to determine the effect of periodized exercise training with and without Cimicifuga racemosa (CR) on bone mineral density (BMD) and 10-year coronary heart disease (CHD) risk in early postmenopausal women.\n A total of 128 women were randomly assigned to three subgroups: exercise (EG, n = 43), exercise and CR supplementation (EGCR, n = 43), and wellness control (control group [CG], n = 42). Both exercise groups performed a periodized exercise program with high-intensity-resistance/high-impact exercise dedicated to bone parameters interspersed by blocks of 10 weeks of training focusing on CHD parameters. In addition to the exercise program, the EGCR was supplemented with 40 mg/day of CR according to the specification of the manufacturer. A low-intensity exercise program of 60 minutes per week for a period of 10 weeks interspersed with 10-week blocks without exercise was performed in the CG. Primary endpoints were BMD and 10-year CHD risk proposed by Wilson. Secondary endpoints were body composition and menopausal symptoms.\n BMD at the lumbar spine was maintained in both exercise groups (EG, -0.1% +/- 2.2%, P = 0.74; EGCR, -0.4% +/- 2.4%, P = 0.40) and significantly decreased (P < 0.001) in the CG (2.0% +/- 2.0%). Both exercise groups significantly differed from the CG (P = 0.001 and 0.005 for the EG and EGCR, respectively); however, no differences between the exercise groups with and without CR was determined. Although slight increases in femoral neck BMD were determined in both exercise groups (EG, 0.5% +/- 3.0%, P = 0.36; EGCR, 0.4% +/- 3.1%, P = 0.52), a reduction was assessed in the CG (-0.6% +/- 2.7%, P = 0.29). No significant differences were determined between the groups. The 10-year CHD risk significantly increased in the EGCR (12.9% +/- 25.1%, P = 0.018) and in the CG (16.5% +/- 27.8%, P = 0.007). The EG did not show corresponding changes (-2.7% +/- 21.9%, P = 0.60). However, no significant between-group differences were observed.\n In conclusion our exercise program favorably affected bone, menopausal symptoms, lean body mass, and, to a smaller extent, 10-year CHD risk in early postmenopausal women. Adjuvant supplementation of CR did not enhance these positive effects.", "Several clinical studies suggest that black cohosh may be effective in climacteric complaints. However, evidence of its efficacy based on current quality standards has been limited.\n This randomized, multicenter, double-blind clinical trial compared the efficacy and tolerability of the isopropanolic black cohosh extract in the treatment of climacteric complaints compared with placebo. A total of 304 patients were randomly allocated to receive tablets corresponding to 40 mg drug or matching placebo daily for 12 weeks. The primary efficacy measure was the change from baseline on the Menopause Rating Scale I; secondary measures included changes in its subscores and safety variables.\n Patient groups did not differ in baseline characteristics. The isopropanolic black cohosh extract was more effective than placebo (P < .001) depending on time from symptom onset (P = .014) and follicle-stimulating hormone level (P = .011). The effect size was 0.03 to 0.05 Menopause Rating Scale units which is similar to recent hormone replacement therapy study results (0.036 Menopause Rating Scale units) and may therefore be considered clinically relevant. Women in the early climacteric phase benefited more than in the late phase. The hot flush subscore was the most effective measure of the isopropanolic black cohosh extract's efficacy. There were no relevant group differences in adverse events, laboratory findings, or tolerability.\n This isopropanolic extract of black cohosh root stock is effective in relieving climacteric symptoms, especially in early climacteric women.", "The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms. A total of 120 healthy women with menopausal symptoms were recruited to this prospective study with a follow-up period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh. After entry into the study, patients were examined at the first, second, third, and sixth months of the treatment period. The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats. In addition, at the beginning and end of the third month, they completed questionnaires consisting of a modified Kupperman Index, Beck's Depression Scale, and a RAND-36 Quality-of-Life Questionnaire. Statistically significant differences were noted in the Kupperman Index and Beck's Depression Scale at the end of the third month in both groups compared with baseline values. In the black cohosh group, the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month. On the other hand, in the fluoxetine group, Beck's Depression Scale decreased significantly compared with that in the black cohosh group. Monthly scores for hot flushes and night sweats decreased significantly in both groups; however, black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine. At the end of the sixth month of treatment, black cohosh reduced the hot flush score by 85%, compared with a 62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued the study--20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh group. Compared with fluoxetine, black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck's Depression Scale.", "Herbal supplements are widely used for vasomotor symptoms.\n To test the efficacy of 3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo.\n 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004.\n Group Health, Washington State.\n 351 women age 45 to 55 years with 2 or more vasomotor symptoms per day; 52% of the women were in menopausal transition and 48% were postmenopausal.\n Rate and intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor Symptom Subscale.\n 1) Black cohosh, 160 mg daily; 2) multibotanical with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo.\n Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale score did not differ between the herbal interventions and placebo at 3, 6, or 12 months or for the average over all the follow-up time points (P > 0.05 for all comparisons) with 1 exception: At 12 months, symptom intensity was significantly worse with the multibotanical plus soy intervention than with placebo (P = 0.016). The difference in vasomotor symptoms per day between placebo and any of the herbal treatments at any time point was less than 1 symptom per day; for the average over all the follow-up time points, the difference was less than 0.55 symptom per day. The difference for hormone therapy versus placebo was -4.06 vasomotor symptoms per day for the average over all the follow-up time points (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001).\n The trial did not simulate the whole-person approach used by naturopathic physicians. Differences between treatment groups smaller than 1.5 Vasomotor symptoms per day cannot be ruled out.\n Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms. Clinical Trials Registration number: NCT00169299.", "In this study, the effects of the Cimicifuga racemosa (CR) preparation CR BNO 1055 on markers of bone metabolism, hormones, sex hormone-binding globulin (SHBG), lipometabolism, vaginal maturity, and routine laboratory parameters were compared with those of conjugated estrogens (CE) and placebo.\n Sixty-two postmenopausal women were included in this double-blind study. Treatment duration with CR (daily dose corresponds to 40 mg of herbal drug), CE (0.6 mg/day), or placebo was 12 weeks. Markers of bone turnover (bone-specific alkaline phosphatase, CrossLaps), estradiol, follicle-stimulating hormone, leuteinizing hormone, SHBG, triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol, and routine clinical chemistry parameters were determined from blood samples. Vaginal \"maturity index\" was determined from vaginal smears.\n The analyses of bone turnover markers indicated beneficial effects for CR and CE on bone metabolism. CR stimulated osteoblast activity, whereas CE inhibited osteoclast activity. Whereas CE showed strong estrogenic effects on vaginal mucosa, CR showed weak estrogen-like activity. No significant effects were seen on coagulation markers and liver enzymes in the blood. CR was well tolerated.\n These results suggest that CR has beneficial bone remodeling and weak estrogen-like effects in the vaginal mucosa.", "To investigate the efficacy-safety balance of the isopropanolic extract of Actaea (=Cimicifuga) racemosa (iCR, Remifemin) in comparison with tibolone in Chinese women with climacteric complaints.\n The randomized, double-blind, controlled 3-month study in 5 centers of 3 cities in China enrolled 244 menopausal patients aged 40-60 years and with a Kupperman Menopause Index (KMI)>or=15. The participants were assigned to either iCR corresponding to 40 mg crude drug/day (N=122) or tibolone 2.5mg/day (N=122) orally. The primary endpoint was the combination of the Mann-Whitney values (MWV) of the KMI and the frequency of adverse events (benefit-risk balance) at end of treatment (MWV>0.5 shows superiority; MWV>0.36 shows non-inferiority).\n KMI decreased from 24.7+/-6.1 to 11.2+/-6.2 and 7.7+/-5.8 (iCR) and to 11.2+/-7.2 and 7.5+/-6.8 (tibolone) at 4 and 12 weeks. This remarkable and clinically relevant improvement was similar in both treatment groups (MWV=0.47; 95% CI=0.39-0.54; p(non-inferiority)=0.002) showing statistical significant non-inferiority of iCR to tibolone. The KMI-responder rate was similar in both groups (84% and 85%). The safety evaluation showed for both groups a good safety and tolerability profile, however, there is a significant lower incidence of adverse events (p<0.0001) in favor of the herbal treatment. None of the postmenopausal iCR patients experienced vaginal bleeding in contrast to tibolone (17 cases). Breast and abdominal pain as well as leukorrhea was mostly observed in the tibolone group (p=0.015, p=0.008, p=0.002). No serious adverse event was observed in the iCR-group, however, two occurred in the tibolone-group. The benefit-risk balance for iCR was significantly (p=0.01) superior to tibolone (MWV=0.56; 95% confidence interval [0.51-0.62]).\n The efficacy of iCR (medicinal product Remifemin) is as good as tibolone for the treatment of climacteric complaints, even for moderate to severe symptoms, whereby iCR is clearly superior regarding the safety profile. This iCR containing medicinal product is an excellent option for treatment of climacteric complaints which has now for the first time been verified in Asian women.", "Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients.\n Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits.\n Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups.\n Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.", "To compare the efficacy and safety of the black cohosh root extract Cr 99 with placebo in women with climacteric complaints.\n A multicenter, randomized, placebo-controlled, double-blind, parallel group study was conducted in 122 menopausal women (intention-to-treat population) with > or =3 hot flashes a day, treated over 12 weeks. Two main efficacy measures - weekly weighted score of hot flashes and Kupperman Index - and secondary efficacy variables, e.g. Menopause Rating Scale, were defined. Routine safety laboratory parameters and adverse events were documented.\n The primary efficacy analysis showed no superiority of the tested black cohosh extract compared to placebo. However, in the subgroup of patients with a Kupperman Index> or =20 a significant superiority regarding this index could be demonstrated (P<0.018). A decrease of 47% and 21% was observed in the black cohosh and placebo group, respectively. The weekly weighted scores of hot flashes (P<0.052) and the Menopause Rating Scale (P<0.009) showed similar results. Prevalence and intensity of the adverse events did not differ in the two treatment groups.\n The results indicate a superiority of the tested Cimicifuga racemosa extract compared to placebo in patients with menopausal disorders of at least moderate intensity according to a Kupperman Index > or =20, but not in the intention-to-treat population as a whole." ]

[ "17382827", "17574448" ]

[ "The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.", "The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures." ]

[ "Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.\n SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.\n For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine.\n Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.", "To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to <17 years) with newly diagnosed partial seizures.\n A multicentre, open-label, randomised, active-control, three-arm, parallel-group, 6-month study. The primary cognitive variable, the Computerized Visual Searching Task (CVST), assessed mental information processing speed and attention. Secondary variables included additional tests assessing psychomotor speed, alertness, memory and learning, and non-verbal intelligence.\n Of 112 patients randomised, 99 completed the study. The dropout rate was 11.6%; 13 patients discontinued due to adverse events (n=5) or unsatisfactory therapeutic effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate.\n Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period." ]

[ "10448545", "11531899", "8536304", "8757005", "16750463", "1330318", "15196302", "8389026", "17157114", "1333181", "1647495", "7954759", "14531480", "7843948", "10943230", "8392150", "1851894", "8393474", "9588435", "7710149", "8879897", "1326404", "1653140", "10210876", "8262783" ]

[ "Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study. The ASASUMAMIG Study Group.", "The efficacy and safety of sc alniditan vs. sc sumatriptan in the acute treatment of migraine: a randomized, double-blind, placebo-controlled trial.", "Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice.", "A comparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the acute treatment of migraine.", "A randomized, double-blind, placebo-controlled trial of the efficacy and tolerability of a 4-mg dose of subcutaneous sumatriptan for the treatment of acute migraine attacks in adults.", "Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study. The Subcutaneous Sumatriptan International Study Group.", "LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.", "Subcutaneous sumatriptan in acute treatment of migraine: a multicentre New Zealand trial.", "Efficacy and tolerability of sumatriptan injection for the treatment of morning migraine: two multicenter, prospective, randomized, double-blind, controlled studies in adults.", "Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.", "Treatment of migraine attacks with sumatriptan. The Subcutaneous Sumatriptan International Study Group.", "A randomized double-blind placebo-controlled crossover study of subcutaneous sumatriptan in general practice.", "Pain-free results with sumatriptan taken at the first sign of migraine pain: 2 randomized, double-blind, placebo-controlled studies.", "Sumatriptan in acute migraine using a novel cartridge system self-injector. United Kingdom Study Group.", "Effectiveness of sumatriptan in reducing productivity loss due to migraine: results of a randomized, double-blind, placebo-controlled clinical trial.", "Efficacy of subcutaneous sumatriptan in repeated episodes of migraine.", "Treatment of acute migraine with subcutaneous sumatriptan.", "Efficacy of subcutaneous sumatriptan in the acute treatment of early-morning migraine: a placebo-controlled trial. Early-Morning Migraine Sumatriptan Study Group.", "Sumatriptan injection reduces productivity loss during a migraine attack: results of a double-blind, placebo-controlled trial.", "Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study.", "Efficacy and tolerability of subcutaneous sumatriptan administered using the IMITREX STATdose System.", "Sumatriptan injection is superior to placebo in the acute treatment of migraine--with regard to both efficacy and general well-being.", "Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device. The Sumatriptan Auto-Injector Study Group.", "Early clinical experience with subcutaneous naratriptan in the acute treatment of migraine: a dose-ranging study.", "Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. French Migraine Network Bordeaux-Lyon-Grenoble." ]

[ "Two-hundred-and-seventy-eight patients with acute migraine attacks with or without aura were treated in 17 centers with 1.8 g lysine acetylsalicylate i.v. (Aspisol; = 1 g acetylsalicylic acid), 6 mg sumatriptan s.c. or placebo using a double-blind, double-dummy, randomized, multicenter parallel group study design. Two-hundred-and-seventy-five of them fulfilled the criteria for efficacy analysis, corresponding to 119 patients treated with lysine acetylsalicylate (L-ASA), 114 with sumatriptan and 42 with placebo injections. Both treatments were highly effective compared to placebo (p < 0.0001) in decreasing headache from severe or moderate to mild or none (verbal rating scale, VRS, placebo = 23.8%). Sumatriptan showed a significantly (p = 0.001) better response (91.2%) compared to L-ASA (response 73.9%). Of the patients in the L-ASA-group, 43.7% were pain-free after 2 h; 76.3% after sumatriptan and 14.3% after placebo. It took patients on average 12.6 (L-ASA), 8.2 (sumatriptan), and 19.4 h (placebo) to be able to work again. There was no significant difference between treatment groups in recurrence of headache in responders within 24 h (18.2% L-ASA, 23.1% sumatriptan, 20% placebo). Accompanying symptoms (nausea, vomiting; photophobia, phonophobia, and visual disturbances) improved with both verum treatments to a similar extent. L-ASA was significantly better tolerated than sumatriptan (adverse events L-ASA 7.6%, sumatriptan 37.8%). In conclusion, subcutaneous sumatriptan and lysine acetylsalicylate i.v. are effective treatments for patients suffering from migraine attacks. Sumatriptan is more effective, but resulted in more adverse events.", "This double-blind, placebo-controlled, parallel-group, multicentre, multinational, phase-III trial was designed to assess the efficacy and safety of a single subcutaneous injection of placebo, 2 doses of alniditan (1.4 mg and 1.8 mg) and 6 mg of sumatriptan in subjects with acute migraine. A total of 114 investigators from 13 different countries screened 2021 subjects. In total 924 patients were treated with placebo (157), alniditan 1.4 mg (309), alniditan 1.8 mg (141) and sumatriptan 6 mg (317). The lower number of subjects in the alniditan 1.8 mg group is due to the termination of this trial arm after the incidence of a serious adverse event and a subsequent protocol amendment. The number of subjects who were pain free at 2 h (primary endpoint) was: 22 (14.1%) with placebo, 174 (56.3%) with alniditan 1.4 mg, 87 (61.7%) with alnditan 1.8 mg and 209 (65.9%) with sumatriptan 6 mg. Alniditan 1.4 mg was significantly better (P < 0.001) than placebo and sumatriptan was significantly better (P = 0.015) than alniditan 1.4 mg. The number of responders (reduction of headache severity from moderate or severe headache before treatment to mild or absent at 2 h), was 59 (37.8%) on placebo, 250 (80.9%) on alniditan 1.4 mg, 120 (85.1%) on alniditan 1.8 mg, and 276 (87.1%) on sumatriptan. Response was significantly higher (P < 0.001) with alniditan 1.4 mg than with placebo, and significantly lower (P = 0.036) with alniditan 1.4 mg than with sumatriptan. Recurrence rates were: 22 (37.3%) with placebo, 87 (34.8%) with alniditan 1.4 mg, 35 (29.2%) with alniditan 1.8 mg and 108 (39.1%) with sumatriptan. Adverse events occurred in 577/924 (62.4%) subjects, i.e. in 62/157 (39.5%) with placebo, 214/309 (69.3%) with alniditan 1.4 mg, 91/141 (64.5%) with alniditan 1.8 mg and 210/317 (66.2%) with sumatriptan 6 mg. Sumatriptan was significantly better than alniditan 1.4 mg for pain free at 2 h. The difference, however, was small and clinically not important. For alniditan, a dose-dependent adverse event relationship was seen. The safety profile of alniditan 1.4 mg was similar to that of sumatriptan.", "A novel self-injector for the administration of subcutaneous sumatriptan in the treatment of migraine attacks was tested in 138 patients recruited by family physicians in Denmark: 108 patients completed the initial double-blind, crossover part of the study. Sumatriptan 6 mg s.c. was significantly better than placebo at 30, 60, 90 and 120 min after injection in relieving moderate or severe headache to mild or none as well as relieving any headache to none. At 60 min after injection, the treatment response rate was 61% for sumatriptan and 6% for placebo. During the following open-phase trial of four attacks treated with sumatriptan, treatment response rates were 68-74%. During the total of 538 attacks treated, 12 attempts at using the self-injector failed. In the double-blind and open phases, 81% and 90% of patients respectively found the device easy or very easy to use. Adverse effects were benign and short-lasting, but led seven patients to discontinue the study. In conclusion, subcutaneous sumatriptan administered with a novel self-injector is an effective treatment for migraine compared to placebo in patients treated by their family physician.", "We compared the efficacy and safety of subcutaneous (SC) sumatriptan (6 mg) with that of dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg) in the acute treatment of migraine. Two hundred sixty-six adult migraineurs (International Headache Society criteria) completed a multicenter, double-blind, double-dummy, cross-over study. Patients took SC sumatriptan for one attack and DHE nasal spray for the other in random order. Data from both treatment periods show that at all time points from 15 minutes, SC sumatriptan was significantly better than DHE nasal spray at providing both headache relief (moderate/severe headache improving to mild/none) and resolution of headache. Similarly, SC sumatriptan was superior to DHE nasal spray for the other efficacy end points assessed in the study. Patients reported that both treatments were well tolerated. Adverse events were reported by 43% of patients taking SC sumatriptan and 22% of patients taking DHE nasal spray. These were usually mild and transient. We conclude that subcutaneous sumatriptan has a faster onset of action than DHE nasal spray and provides greater relief of acute migraine symptoms.", "The aim of this study was to evaluate the efficacy and tolerability of a single 4-mg dose of sumatriptan SC for the acute treatment of adult patients experiencing a migraine attack with moderate to severe pain.\n In this randomized, double-blind, placebo-controlled study, subjects included men and women aged 18 to 60 years who had migraine with or without aura, as defined by the 1988 International Headache Society criteria. Subjects received either sumatriptan 4 mg SC or placebo SC for a migraine attack with headache pain of moderate to severe intensity. The primary efficacy measurement was pain relief at 2 hours. Secondary efficacy measures included the severity of headache pain at 10, 20, 30, 40, 50, 60, and 90 minutes postadministration. Clinical assessments of pain severity and adverse events were made by way of questioning and observation of subjects and were completed at 10, 20, 30, 40, 50, 60, 90, and 120 minutes postadministration.\n Five hundred seventy-seven subjects (87% female and 94% white) participated in this study. Three hundred eighty-four received sumatriptan and 193 received placebo. At 120 minutes postadministration, sumatriptan 4 mg SC was associated with greater proportions of patients who experienced pain relief (70% vs 22%; P<0.001) or were pain free (50% vs 11%; P<0.001). In addition, there were statistically significant differences between sumatriptan 4 mg SC and placebo for multiple secondary end points, including pain relief as early as 10 minutes postadministration (11% vs 6%; P=0.039), pain-free status as early as 30 minutes postadministration (10% vs 3%; P<0.001), nausea as early as 30 minutes postadministration (39% vs 49%; P=0.021), and photophobia as early as 10 minutes postadministration (80% vs 87%; P=0.046). The most common adverse events in the sumatriptan 4-mg SC and placebo groups, respectively, were injection-site reactions (43% and 15%), tingling (12% and 3%), dizziness or vertigo (10% and 5%), and warm or hot sensation (8% and 2%). Treatment groups were not statistically compared for adverse events.\n Sumatriptan 4 mg SC was effective for the acute treatment of migraine attacks and was generally well tolerated in these patients.", "The results of the very first large-scale placebo-controlled dose-response trial with the novel selective 5-hydroxytryptamine1-like (5HT1-like) receptor agonist sumatriptan are presented. We studied the efficacy and tolerability of subcutaneous injections of 1 mg, 2 mg and 3 mg of sumatriptan in alleviating migraine attacks in a double-blind, placebo-controlled, parallel-group, multicentre clinical trial. Six-hundred and ninety patients were randomized and 685 received study medication. At 30 min, reduction of headache severity to mild or none (primary efficacy endpoint) was achieved in 22% (95% CI: 15-28%) of placebo-treated patients and in 39% (CI: 31-46%) of patients treated with 1 mg sumatriptan, 44% (CI: 36-51%) treated with 2 mg sumatriptan and 55% (CI: 48-63%) treated with 3 mg sumatriptan. Differences from placebo were 17% (CI: 8-27%) for 1 mg sumatriptan, 22% (CI: 13-32%) for 2 mg sumatriptan and 34% (CI: 24-44%) for 3 mg sumatriptan (p < 0.001 for all three comparisons). Other migraine symptoms were also more effectively treated by sumatriptan than by placebo. Subsequently, an open-label 3 mg dose subcutaneous sumatriptan was given to partial or non-responders. Thirty minutes after this open dose the response rate to sumatriptan had improved to between 70 and 80%. Adverse events after sumatriptan were minor and short-lived. We conclude that subcutaneous sumatriptan is well tolerated in doses up to 3 + 3 mg and may rapidly abort migraine attacks.", "Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age +/- SD = 40 +/- 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.", "To assess the effectiveness of subcutaneous sumatriptan (4 mg) in the acute treatment of migraine.\n A randomised, double-blind, placebo controlled study was conducted in four New Zealand centres. On developing an acute attack of migraine, patients attended a centre where they were given either sumatriptan 4 mg or placebo by subcutaneous injection. Headache severity and clinical disability were measured over a 2 hour period.\n Fifty-one patients, aged 19-58 years with common or classical migraine were treated. Twenty-eight patients received 4 mg sumatriptan and 23 patients received placebo. Pretreatment headache severity was graded moderate in 76% and severe in 24%. Thirty-two percent of patients were sufficiently disabled to require bed rest and a further 48% had severe impairment of working ability. Sumatriptan was significantly more effective than placebo in relieving or reducing headache severity after 30 minutes. Sixty-four percent improved on sumatriptan compared to 27% on placebo. Functional disability, nausea, vomiting and photophobia were also greatly reduced. Adverse effects occurred in 17% of patients receiving placebo, and 82% receiving sumatriptan, the commonest being injection site reactions.\n Subcutaneous sumatriptan 4 mg is an effective and well-tolerated acute treatment in adult patients with moderate to severe common or classical migraine. The efficacy rate of 64% is lower than that found in recent controlled studies using a higher dose.", "The aim of this study was to assess the efficacy and tolerability of sumatriptan injection in the treatment of morning migraine.\n In 2 multicenter (20 sites for study 1 and 25 sites for study 2), randomized, double-blind, controlled, parallel-group studies, male and female patients aged 18 to 65 years with migraine meeting International Headache Society criteria received SC sumatriptan succinate injection 6 mg or inactive vehicle (control) for the outpatient treatment of a single morning migraine, defined as migraine with moderate or severe pain on awakening. The primary end point was the percentage of patients who achieved pain-free relief (moderate or severe pain reduced to no pain) at 2 hours after treatment. Tolerability was assessed using spontaneous reporting or noted by a clinician during the studies, assessed at the return visit.\n The efficacy analysis included, in the succinate group, 145 patients in study 1, 148 in study 2; control, 152 in study 1, 139 in study 2. The mean (SD) ages in the sumatriptan group were 40.2 (9.7) and 38.8 (10.1) years in studies 1 and 2, respectively; control, 41.4 (10.4) and 39.3 (9.7) years. The majority of patients in the 2 studies were female (sumatriptan, 84% and 93% in studies 1 and 2, respectively; control, 82% and 81%) and white (sumatriptan, 83% and 81%; control, 78% and 89%). Two hours after treatment, 48% and 57% of patients treated with sumatriptan injection compared with 18% and 19% of control patients reported pain-free relief in studies 1 and 2, respectively (both, P < 0.001). Two hours after treatment, 72% and 77% of patients treated with sumatriptan injection reported headache relief (moderate or severe pain reduced to mild or no pain) compared with 32% and 41% of control patients (both, P < 0.001). Onset of efficacy versus control (the first time point with statistical significance of pain relief) was observed beginning 10 minutes postdose (P < 0.05 sumatriptan injection vs placebo across pooled studies). Mean time to efficacy in the sumatriptan group was 10 minutes (P < 0.05 vs controls). The most commonly reported adverse events were nausea (sumatriptan, 6% and 4%; control, 2% and 2%) and injection-site reaction (ie, burning or stinging at the injection site) (sumatriptan, 5 % and 5%; control, 2% and 1%). Injection-site reaction was also the only adverse event considered treatment related and reported in > or =5 % of all patients.\n The results of these 2 randomized, double-blind, controlled studies suggest that sumatriptan injection was effective and well tolerated in the acute treatment of morning migraine in these adults.", "Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.", "The headache in migraine attacks may be caused by dilatation of certain cranial arteries or arteriovenous anastomoses, by neurogenic dural plasma extravasation, or by both of these mechanisms. Sumatriptan, a novel selective agonist of 5-hydroxytryptamine-like receptors, blocks these phenomena. We investigated its efficacy in migraine.\n We studied 639 patients with migraine attacks in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. We assessed the effect of subcutaneous injections of 6 or 8 mg of sumatriptan or placebo on the severity of headache and associated migrane symptoms 30, 60, and 120 minutes after treatment. Patients who were not free of pain after 60 minutes subsequently received placebo if they had initially received placebo or 8 mg of sumatriptan, and 6 mg of sumatriptan or placebo if they had initially received 6 mg of sumatriptan.\n After 60 minutes, the severity of headache was decreased in 72 percent (95 percent confidence interval, 68 to 76 percent) of the 422 patients given 6 mg of sumatriptan, 79 percent (95 percent confidence interval, 71 to 87 percent) of the 109 patients given 8 mg of sumatriptan, and 25 percent (95 percent confidence interval, 17 to 33 percent) of the 105 patients given placebo (data on 3 patients could not be evaluated). As compared with the placebo group, 47 percent (95 percent confidence interval, 38 to 57 percent) more patients who had received 6 mg of sumatriptan and 54 percent (95 percent confidence interval, 43 to 65 percent) more patients who had received 8 mg of sumatriptan had a decrease in the severity of headache (P less than 0.001 for both comparisons). After 120 minutes, 86 to 92 percent of the 511 patients treated with sumatriptan (202 assigned to 6 mg plus placebo, 203 to 6 mg plus 6 mg, and 106 to 8 mg plus placebo) had improvement in the severity of headache, as compared with only 37 percent of the 104 patients who received placebo once or twice (P less than 0.001 for all comparisons). Twenty-one patients were excluded from the analysis because of missing data (19) or protocol violations (2). The response rates did not differ significantly among the sumatriptan regimens. Adverse events were minor and transient in all groups.\n We conclude that a single 6-mg dose of sumatriptan given subcutaneously is a highly effective, rapid-acting, and well-tolerated treatment for migrane attacks. The administration of a second dose 60 minutes later to patients not responding well to an initial dose affords little additional benefit.", "To evaluate the therapeutic response to sumatriptan in the acute migraine attack,\n Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included in the study. The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo for the first attack and the alternative medication, i.e. placebo or sumatriptan, for the second attack (crossover). Following treatment, a neurology resident interviewed and examined the patients.\n When sumatriptan was compared to placebo, significantly more of the 209 evaluable patients reported headache relief at 1 h (56% vs 8%, p < 0.001) and 2 h (62% vs 15%, p < 0.001) after the first injection. Resolution of nausea, photophobia, and phonophobia was significantly more common in patients on sumatriptan than in those on placebo (p < 0.001 for all comparisons). The adverse events were usually transient and of mild or moderate severity; however, three patients withdrew due to adverse events. Ninety-five percent of patients evaluated by a neurology resident met the IHS criteria for migraine.\n In general practice, sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine.", "To evaluate the efficacy and tolerability of sumatriptan, 50-mg and 100-mg tablets, compared with placebo for treatment of migraine at the first sign of pain.\n Two identical multicenter randomized, double-blind, placebo-controlled, single-attack studies were conducted from May through November 2000 in adults (aged 18-65 years). Patients treated migraine at the first sign of pain, while pain was mild, but not more than 2 hours after onset with oral sumatriptan, 50 mg or 100 mg, or matching placebo. The primary end point was pain-free relief at 2 hours after treatment with 50 mg of sumatriptan compared with placebo.\n There were 354 patients in study 1 and 337 patients in study 2. Significantly more patients treated with sumatriptan, 50 mg and 100 mg, were completely free from pain 2 and 4 hours after treatment vs patients treated with placebo (at 2 hours, 50% and 57% vs 29%; at 4 hours, 61% and 68% vs 30%; for both, P < .001). Also, significantly more patients treated with sumatriptan, 50 mg and 100 mg, were migraine-free (no pain or associated symptoms) vs those treated with placebo at 2 and 4 hours after treatment (at 2 hours, 43% and 49% vs 24%; at 4 hours, 54% and 63% vs 28%; for both, P < .001). The incidence of overall adverse events was low with the 50- and 100-mg dose of sumatriptan (placebo, 7%; sumatriptan at 50 mg, 14%; sumatriptan at 100 mg, 16%).\n Treatment of migraine at the first sign of pain with sumatriptan, 50-mg and 100-mg tablets, provides superior pain-free relief at 2 and 4 hours after treatment compared with placebo. Results of these studies suggest that sumatriptan at 100 mg may be more efficacious than at 50 mg when used in the early treatment paradigm. Because these studies were not powered to detect statistical differences between active doses, studies to investigate this finding are warranted.", "This double-blind, randomized, placebo-controlled, parallel-group, multicenter study assessed the efficacy, acceptability, safety, and tolerability of subcutaneous sumatriptan 6 mg administered using a novel cartridge system self-injector for the acute treatment of migraine. Eighty-six patients treated one migraine attack at home with sumatriptan or placebo. A second identical injection was available after 1 hour for inadequate relief or if the headache recurred. Rescue medication was available 1 hour later. The primary end point was headache relief (improvement in headache from moderate or severe to mild or no pain) within 60 minutes of the first injection. Secondary end points included the acceptability of the self-injector, requirement for and efficacy of a second dose, relief of nonheadache symptoms, use of rescue medication, and adverse events. Significantly more patients taking sumatriptan than placebo reported headache relief 1 hour after the first injection (88% vs 11%, P < 0.001). The device was well accepted by patients; about 90% found it easy to use and wanted to take further medication using it. Significantly fewer patients taking sumatriptan than placebo required a second injection (33% vs 92%, P < 0.001) or rescue medication after the second injection (35% vs 67% P < 0.05). Significantly more patients taking sumatriptan than placebo reported headache relief after the second injection (83% vs 32%, P < 0.01), and resolution of nonheadache migraine symptoms (54% vs 23%, P < 0.01). Sumatriptan was generally well tolerated. Subcutaneous sumatriptan 6 mg self-administered using the novel self-injector is an effective, well accepted, and well tolerated acute treatment of migraine.", "To determine the effect of sumatriptan on migraine-related workplace productivity loss.\n In this randomized, double-blind, placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of sumatriptan or matching placebo to treat a moderate or severe migraine within the first 4 hours of a minimum of an 8-hour work shift. Outcome measures included productivity loss and number of patients returning to normal work performance 2 hours after injection and across the work shift, time to return to normal work performance, and time to headache relief.\n A total of 206 patients underwent screening, 140 (safety population) of whom returned for clinic treatment. Of these 140 patients, 119 received migraine treatment in the workplace (intent-to-treat population), 116 of whom comprised the study population. Of these 116 patients, 76 self-administered sumatriptan, and 40 self-administered placebo. Sumatriptan treatment tended to reduce median productivity loss 2 hours after injection compared with placebo (25.2 vs 29.9 minutes, respectively; P = .14). Significant reductions in productivity loss were obtained across the work shift after sumatriptan treatment compared with placebo (36.8 vs 72.6 minutes, respectively; P = .001). Significantly more sumatriptan-treated patients vs placebo-treated patients experienced shorter return to normal work performance at 2 hours (53/76 [70%] vs 12/40 [30%], respectively) and across the work shift (64/76 [84%] vs 23/40 [58%], respectively; P < .001). Significantly more sumatriptan-treated patients experienced headache relief 1 hour after injection compared with placebo-treated patients (48/76 [63%] vs 13/40 [33%], respectively; P = .004).\n Across an 8-hour work shift, sumatriptan was superior to placebo in reducing productivity loss due to migraine.", "This double-blind, placebo-controlled, multicenter, crossover study investigated the efficacy and tolerability of sumatriptan administered for up to three separate migraine attacks. One hundred twenty adults received sumatriptan (SC, 6 mg; three attacks) and placebo (one attack). Patients completed questionnaires assessing the impact of migraine on their lives and the performance of sumatriptan relative to their usual acute therapies. Sumatriptan statistically outperformed placebo on all efficacy measures, including pain severity; presence/absence of nausea, vomiting, phonophobia, and photophobia; rescue medication use; and clinical disability. Efficacy was consistently maintained with repeated administration. For all attacks, pain relief 90 minutes postdose occurred in 86% to 90% of sumatriptan-treated patients, compared with 9% to 38% of placebo-treated patients. Sumatriptan was well tolerated, and the frequency and severity of adverse events did not change with repeated administration. Patients' perceptions of sumatriptan were consistent with clinical data demonstrating the drug's high degree of efficacy and tolerability.", "Sumatriptan succinate, a 5-HT1D receptor agonist, constricts human cranial arteries. Two parallel-group trials for treatment of acute migraines were conducted in the United States. Adult patients were randomized and given either 6 mg of sumatriptan succinate subcutaneously (n = 734) or placebo (n = 370). At 1 hour, sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain (70% vs 22%), in completely relieving headaches (49% vs 9%), and in improving clinical disability (76% vs 34%). Sumatriptan also reduced nausea and photophobia significantly better than placebo. Patients with residual migraines received another injection; those who had originally received sumatriptan received either a second active injection (n = 187) or placebo (n = 178), while those who had received placebo received a second placebo injection (n = 335). Statistical evidence for benefit of second sumatriptan injection is absent. Adverse events associated with sumatriptan were tingling, dizziness, warm-hot sensations, and injection-site reactions. Sumatriptan is effective and well tolerated in patients with acute migraine.", "To evaluate the efficacy of self-administered subcutaneous sumatriptan in the acute treatment of early-morning migraine attacks.\n A double-blind, randomized, placebo-controlled, cross-over study.\n Thirteen neurology centres in France.\n Patients of either sex, 18-65 years old, with two to six attacks of migraine (according to the International Headache Society (IHS) criteria, with or without aura) per month, of which at least two had to be early-morning migraine attacks. One-hundred-and-one patients were included, 96 being evaluable for the first attack and 81 for the cross-over design.\n Two migraine attacks (grade 2/3) were treated with sumatriptan (6 mg) or placebo, with an optional second injection 1-24 h later. Main outcome measures. The primary end-point was headache relief: reduction in headache severity from grade 2/3 (moderate/severe) to grade 1/0 (mild/none) 2 h after treatment.\n Sumatriptan was superior to placebo for headache relief (32 [78%] vs. 11 [28%] at the first attack; 29 [73%] vs. 8 [20%] at the second; P < 0.001). Because of a significant carry-over effect for some of the secondary end-points, a parallel-group analysis of the first attack was performed, which confirmed a significantly higher efficacy of sumatriptan for all end-points: pain-free rate (22 [46%] vs. 7 [15%]; P = 0.001) and use of a second injection (26 [53%] vs. 38 [81%]; P = 0.004). Sumatriptan was preferred by 74% of patients vs. 17% for placebo, and 9% expressed no preference (P < 0.0001). After complete relief, headache reappeared in 8/23 (35%) patients with sumatriptan and 3/7 (43%) with placebo. Adverse events were significantly more frequent with sumatriptan but they were minor and transient.\n Subcutaneous sumatriptan auto-injection is an effective and well-tolerated acute treatment of early-morning migraine attacks allowing earlier return to normal activity.", "To evaluate the impact of sumatriptan succinate injection compared with placebo on productivity loss during a migraine attack in the workplace.\n Randomized, double-blind, placebo-controlled, parallel-group clinical trial.\n Fifteen clinical centers in the United States.\n One hundred thirty-five patients 18 years and older diagnosed as having migraine according to International Headache Society criteria.\n Patients self-administered sumatriptan injection (6 mg) or matching placebo to treat a moderate or severe migraine occurring within the first 4 hours of a minimum 8-hour work shift.\n Mean productivity loss 2 hours after dosing and across the work shift; percentages of patients returning to normal work performance within 2 hours after dosing and across the work shift; percentages of patients experiencing headache relief (reduction of moderate or severe predose pain to mild or no pain) 1 and 2 hours after dosing.\n Mean productivity loss was significantly (P< or =.002) lower in the sumatriptan group compared with the placebo group both during the 2-hour postdose period (sumatriptan, 39 minutes; placebo, 54 minutes) and across the work shift (sumatriptan, 86 minutes; placebo, 168 minutes). Significantly (P<.001) greater percentages of patients in the sumatriptan group compared with the placebo group returned to normal work performance by 2 hours after dosing (sumatriptan, 52%; placebo, 9%) and across the work shift (sumatriptan, 66%; placebo, 18%). Significantly (P< or =.001) greater percentages of patients in the sumatriptan group compared with the placebo group experienced headache relief 1 hour after dosing (sumatriptan, 69%; placebo, 18%) and 2 hours after dosing (sumatriptan, 79%; placebo, 32%).\n Sumatriptan reduced migraine-associated productivity loss during a minimum 8-hour work shift by approximately 50% compared with placebo and alleviated headache in more than three fourths of patients.", "To assess the efficacy of SC sumatriptan injection versus placebo in the treatment of acute migraine in ED patients and that of open-label 100 mg sumatriptan PO tablets for recurrent migraine.\n Randomized, double-blind, placebo-controlled, multi-center trial.\n Twelve EDs in the United States.\n Adult patients presenting to the ED from September 1992 through April 1993 with a diagnosis of migraine as determined by International Headache Society criteria. Patients were randomized to receive 6 mg sumatriptan SC or placebo. Patients were monitored for improvement in headache severity using a four-point scale and for time to meaningful relief using a stopwatch. The time to discharge from the ED was recorded. An open-label 100 mg sumatriptan PO tablet was given to all patients on discharge from the ED for use at home if the headache recurred within 24 hours.\n One hundred thirty-six patients were enrolled. Seventy-five percent of patients treated with sumatriptan achieved meaningful relief compared with 35% treated with placebo (P < .001). The median time to meaningful relief was 34 minutes in the group that received sumatriptan. Seventy percent of patients in the sumatriptan group versus 35% in the placebo group reported mild or no pain at discharge (P < .001). Migraine-associated symptoms such as nausea, photophobia, and phonophobia were significantly reduced in the sumatriptan group (P < .005). The median time to discharge from the ED was shorter for the sumatriptan group than for the placebo group (60 versus 96 minutes, respectively; P = .001). At baseline, 15% of patients in the sumatriptan group and 19% of patients in the placebo group reported mild or no clinical disability. At the time of discharge, patients with mild or no disability increased to 75% in the sumatriptan group compared with 44% in the placebo group (P = .001). Fifty-seven of 92 patients (62%) with mild or no pain at discharge took open-label oral sumatriptan for headache recurrence, and 37 (65%) experienced meaningful relief within 2 hours. Median time to meaningful relief after oral sumatriptan was 65 minutes.\n Sumatriptan (6 mg SC) is effective in treating acute migraine in the ED. Oral sumatriptan (100 mg) is effective in treating headache recurrence within 24 hours.", "The efficacy and tolerability of subcutaneous (SC) sumatriptan administered with the IMITREX (sumatriptan succinate) STATdose System, which circumvents the need for patients or health care professionals to handle a syringe, were evaluated in two randomized, double-masked, parallel-group, placebo-controlled, multicenter studies. In the clinic, 158 adults with migraine diagnosed according to International Headache Society criteria received SC sumatriptan (6 mg) or placebo delivered with the IMITREX STATdose System for treatment of a migraine attack. By 120 minutes after SC dosing, 73% and 79% of sumatriptan-treated patients, compared with 28% and 37% of placebo-treated patients in studies 1 and 2, respectively, experienced headache relief (a statistically significant difference). Clinical disability scores 120 minutes after dosing showed that 75% and 85% of sumatriptan-treated patients, compared with 30% and 42% of placebo-treated patients, were normal or only mildly impaired (a statistically significant difference). Similar efficacy rates were observed for nausea, phonophobia, and photophobia. No serious or unusual adverse events occurred, and no clinically relevant abnormalities in laboratory test values were reported. Based on these results, we concluded that SC sumatriptan (6 mg) administered using the IMITREX STATdose System is effective for the treatment of migraine. The efficacy and tolerability profiles of SC sumatriptan administered with this device are similar to those reported for SC sumatriptan administered with a conventional syringe.", "The efficacy of subcutaneous injection of sumatriptan in the acute treatment of migraine was assessed in a double-blind, randomized, placebo-controlled cross-over study of 27 migraine patients. In addition, the patients were asked to give information about their well-being and subjective symptoms by means of a self-administered standardized questionnaire. A total of 22 migraine sufferers received a subcutaneous (sc) injection of 8 mg of sumatriptan and 24 received placebo. Of these patients, 19 received both treatments and thus completed the study. The primary efficacy end-point was a reduction in headache severity from severe or moderate to mild or no headache at 30, 60, 90 and 120 min. An effective response to treatment was achieved within 30 min in 63% and within 60 min in 84% of patients when treated with 8 mg sumatriptan sc, compared with 11% for placebo (p less than 0.001). Sumatriptan also provided significant relief from nausea and photophobia as compared with placebo. The proportion of patients that needed rescue medication after 120 min was significantly lower (p less than 0.001) with active treatment when compared with placebo. Sumatriptan was well tolerated and the majority of adverse events were mild and transient. The most frequent symptoms were those of malaise/fatigue or numbness. No changes in blood pressure or ECG readings were observed during the treatment. Compared with placebo, subcutaneous 8 mg sumatriptan also caused a substantial improvement in general well-being as revealed by the Minor Symptoms Evaluation Profile-acute (MSEP-acute) questionnaire.(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy and safety of sumatriptan, a selective 5-HT1-like receptor agonist, were studied in a randomized, double-blind, placebo-controlled, parallel-group, multicentre, multinational clinical trial of 235 patients suffering a moderate to severe migraine attack. Patients were randomized to treat a single migraine attack at home with 6 mg sumatriptan or placebo using an auto-injector. If the migraine had not improved at 1 h, patients had the option of taking a second identical injection. The primary measure of treatment efficacy was based on a comparison of the number of patients in the two treatment groups who had a reduction in headache severity from severe or moderate to mild or none at 1 and 2 h. At 1 h, 77% of patients treating with 6 mg sumatriptan compared to 26% treating with placebo (p less than 0.001) had mild headache or none. At 2 h, the response rates for all patients had risen to 83 and 30%, respectively. Of those patients requiring a second dose at 1 h, improvement to mild or no headache at 2 h was achieved in 61% of patients receiving sumatriptan compared to 15% of those receiving placebo. Other migraine symptoms were more effectively treated by sumatriptan and patients were able to return to work or normal activities earlier. Migraine recurrence within 48 h was a feature of 46% of attacks treated by patients with either treatment. Adverse events were more frequent using sumatriptan but were minor and transient.(ABSTRACT TRUNCATED AT 250 WORDS)", "Naratriptan is a novel, potent agonist at the 5HT1B/1D receptor. A total of 335 migraine patients were treated in this randomized, double-blind, placebo-controlled, dose-ranging, in-clinic study, to evaluate the efficacy, safety and tolerability of five doses of subcutaneous (sc) naratriptan (0.5, 1, 2.5, 5 or 10 mg) in comparison with sc sumatriptan (6 mg) and placebo in the acute treatment of a moderate/severe migraine attack. Headache relief [reduction of headache severity from moderate or severe (grade 2/3) to mild or none (grade 1/0)] at 1 and 2 h after each dose, was reported by a statistically significantly higher proportion of patients for all doses of sc naratriptan and sc sumatriptan (6 mg) than for placebo. The percentages of patients with headache relief at 2 h post-dose were: naratriptan (0.5 mg) 65%, (1 mg) 75%, (2.5 mg) 83%, (5 mg) 94% and (10 mg) 91%; sumatriptan (6 mg) 89%; placebo 41%, (P < 0.005). The earliest report of a statistically significant difference compared with placebo for the times assessed was with sc naratriptan (10 mg) at 10 min post-dose (P = 0.023). The percentages of patients reporting adverse events were dose-related; sc naratriptan (0.5 mg) 33%, (1 mg) 29%, (2.5 mg) 43%, (5 mg) 59% and (10 mg) 71%; sc sumatriptan 53%; placebo 22%. There were no clinically significant changes in electrocardiogram (ECG), vital signs or laboratory parameters. Systemic exposure increased proportionally to the dose, the absorption of sc naratriptan was rapid (tmax = 10 min) and the half-life was 5 h. In conclusion, sc naratriptan was an effective and well-tolerated acute treatment for migraine. Copyright 1998 Lippincott Williams & Wilkins", "The efficacy of sumatriptan, a 5-HT1 receptor agonist, in patients with migraine attacks occurring despite prophylactic treatment with oral dihydroergotamine, was assessed in a double-blind placebo-controlled study involving 76 patients. Thirty-seven patients were treated with a subcutaneous injection of 6 mg sumatriptan self-administered with an auto-injector and 39 with placebo given by the same route. Patients having inadequate relief were allowed to use a second injection of test medication 1 hour later and rescue treatment between 2 hours and 24 hours after the first dose. Headache relief was achieved within 2 hours after sumatriptan in 26 patients (70%) compared to 8 patients (21%) in the placebo group (P < 0.0001). Of these patients, 19 (51%) and 3 (8%) were, respectively, pain free at this time. A second injection of sumatriptan was used by 8 (22%) patients compared to 30 (77%) patients in the placebo group (P < 0.0001), whereas rescue medication was used respectively by 13 (35%) and 22 (58%) patients (P < 0.024). The adverse event profile of sumatriptan was not affected by the concomitant use of dihydroergotamine and side-effects were all minor and transient. Patient satisfaction was significantly higher in the sumatriptan group (75%) compared to patient satisfaction with placebo (16%). These results show that the high efficacy rate of subcutaneous sumatriptan and its safety profile remain unchanged in migraine patients receiving oral dihydroergotamine as prophylaxis." ]

[ "3552457", "3552455", "12175719", "6529546", "12468168", "11264625", "6397856" ]

[ "Comparison of two formulations of lignocaine spray with mefenamic acid in the relief of post-episiotomy pain: a placebo-controlled study.", "Evaluation of two local anaesthetic sprays for the relief of post-episiotomy pain.", "Effects of indomethacin suppository and lidocaine pomade for the relief of post-episiotomy pain.", "Clinical evaluation of a topical anaesthetic preparation (pramoxine hydrochloride and hydrocortisone) in post-episiotomy pain relief.", "Randomized trial of lidocaine ointment versus placebo for the treatment of postpartum perineal pain.", "Reducing postnatal pain from perineal tears by using lignocaine gel: a double-blind randomized trial.", "Topical pramoxine and hydrocortisone foam versus placebo in relief of post partum episiotomy symptoms and wound healing." ]

[ "The analgesic effectiveness of aqueous and alcoholic formulations of lignocaine (5%) spray was compared with that of mefenamic acid (500 mg) or placebo in a double-blind study in 103 primiparous patients complaining of moderate or severe perineal pain associated with episiotomy. The results, assessed after a single dose, showed that the aqueous lignocaine formulation provided a level of pain relief superior to that obtained with the alcoholic formulation or placebo, and similar to that obtained with mefenamic acid.", "Aerosol formulations of lignocaine (5%) and cinchocaine (2%) were compared with a water-only placebo spray in a single-dose study in 76 primiparous patients complaining of moderate or severe post-episiotomy pain. In comparison with a water-only placebo, both local anaesthetic formulations gave significant relief when administered to the perineal wound but the lignocaine spray proved to be the more effective. The only side-effect reported was slight stinging occurring immediately after administration of the lignocaine spray in 2 cases. Serum concentrations of local anaesthetic post-administration were negligible. An interesting finding was that breast-feeding patients responded less well to this form of analgesia than patients in whom lactation had been suppressed with frusemide.", "nan", "nan", "To estimate the efficacy of lidocaine ointment in relieving pain after a vaginal delivery with an episiotomy or perineal laceration.\n In a randomized, double-blind, placebo-controlled trial, 200 women received lidocaine ointment (n = 108) or a placebo (n = 92). Pain relief was assessed by the amount of ointment used (weight of jar before use - weight of jar after use), total number of pain pills used, and a pain questionnaire. The sample size was calculated using a beta of.2 and an alpha of.05 with an expected reduction of other pain medications from an average use of six pills to four pills for the population.\n There was no significant difference in the amount of lidocaine versus placebo used for postpartum day 1 (5.1 g versus 4.0 g, respectively [P =.13]) or day 2 (3.7 g versus 2.6 g, respectively [P =.18]). Patients receiving lidocaine instead of the placebo showed no significant difference in the total amount of postpartum pain medications (6.3 versus 6.8 tablets, respectively [P =.53]), subjective pain parameters (P =.36), or satisfaction from ointment (P =.99). Patients with an episiotomy used more pain medications than those with a laceration (7.9 versus 5.6 tablets, respectively [P =.003]). Those with minor versus major lacerations required fewer pain pills (6.1 versus 10.8 tablets, respectively [P <.001]) and used less ointment (4.3 g versus 7.9 g, respectively [P =.02]) on the first postpartum day.\n Topical application of 5% lidocaine ointment was not effective in relieving episiotomy or perineal laceration pain.", "Perineal pain is one of the most common causes of maternal morbidity in the early puerperium. Several randomized trials have shown that topical application of local anesthetics is effective in reducing postepisiotomy pain, but no randomized study has assessed the efficacy of local anesthetics for other perineal trauma. This study investigated if topically applied 2 percent lignocaine gel was an effective treatment for this group of women.\n A double-blind placebo controlled trial was conducted in a regional teaching hospital in the northwest of England. One hundred and forty-nine women who had sustained a first- or second-degree tear were allocated by sealed envelopes to the lignocaine gel or placebo group. The primary outcome was self-reported pain at 24 hours postdelivery as measured on a numerical rating scale (pain score). Secondary outcomes included pain scores at 48 hours, the need for oral analgesia, and maternal satisfaction. Based on a pilot study, we calculated that 128 women were required to detect a 25 percent difference in pain scores between the two groups with 80 percent power (alpha = 0.05). The pain scores of women in each trial arm were compared using the unpaired t test and 95 percent confidence intervals.\n Women using lignocaine gel had lower average pain scores, although this only reached statistical significance at 48 hours after delivery (p = 0.023). In general, women liked using the study gel. No difference was found in consumption of oral analgesia.\n This study suggested that lignocaine gel may be effective on the second postnatal day. Further research is required to assess the optimum timing of this intervention and the population that would most benefit from its use.", "A double-blind randomised controlled trial, comparing pramoxine hydrochloride 1 per cent and hydrocortisone acetate 1 per cent in a mucoadhesive foam base, with simple aqueous foam (B.P.), in relieving episiotomy discomfort and episiotomy healing in 40 patients was carried out. Simple aqueous foam was more effective with regard to wound healing and episiotomy discomfort as measured by analgesic consumption. Pramoxine and hydrocortisone foam offers no advantage over simple aqueous foam in the treatment of post partum episiotomy discomfort." ]

[ "3276865", "9299856", "11111812", "4717585", "15801959", "3153025", "3183852", "12966125", "2062330", "9543364", "11309826", "6372729" ]

[ "Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial.", "Antiplatelet agents in thrombotic thrombocytopenic purpura (TTP). Results of a randomized multicenter trial by the Italian Cooperative Group for TTP.", "Design of the prospective randomized study for the treatment of patients with thrombotic microangiopathy. PRODROMI Study Group.", "Heparin therapy in the hemolytic-uremic syndrome.", "Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet.", "Treatment of the childhood haemolytic uraemic syndrome with plasma. A multicentre randomized controlled trial. The French Society of Paediatric Nephrology.", "Heparin plus dipyridamole in childhood hemolytic-uremic syndrome: a prospective, randomized study.", "Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial.", "Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group.", "Steroids in the hemolytic uremic syndrome.", "Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP).", "[Treatment of childhood hemolytic-uremic syndrome with urokinase. Cooperative controlled trial]." ]

[ "The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome (HUS) are reported. Criteria for admission were (1) observation within 8 days from first symptoms, (2) dialysis treatment required, and (3) no special treatments and no more than 25 ml blood/kg previously received. Children were subdivided according to age (less than or more than 3 years) and then randomly assigned to treatment with plasma or symptomatic therapy. Thirty-two children ranging in age from 4 months to 6 years entered this study; 17 received plasma (P+ group) and 15 only symptomatic therapy (P- group). The mean follow-up period was 16 months in both groups. Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children, and 33 histologic findings were semiquantitatively evaluated. No death occurred in either group. No differences were found in blood pressure, proteinuria, or hematuria at the end of the follow-up period; in no case were severe arteriolar lesions found. There were no significant differences for the scores of the individual histologic measurements; on electron microscopy, no vascular changes were observed in seven children of the P+ group, whereas in five of seven of the P- group, thickening of the lamina rara interna and arteriolar damage were present. The ability of plasma to stimulate prostacyclin (PGI2) production, measured as its stable derivative 6-keto-PGF1 alpha, was within the normal range for all patients. In our patients with predominant glomerular involvement who were treated in a very early phase of HUS, infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease. A longer follow-up is needed to ascertain whether the presence of endothelial damage, demonstrated by electron microscopy in children who were not given plasma, is of clinical relevance.", "Antiplatelet agents are often included in plasma exchange-based regimens for thrombotic thrombocytopenic purpura (TTP) patients; however, the opportuneness of their use in TTP is still controversial. The italian Cooperative Group for TTP carried out a randomized trial to investigate their actual effectiveness, both in acute TTP and as maintenance treatment.\n Seventy-two TTP patients were randomized to receive plasma exchange and steroids with (group B) or without (group A) aspirin and dipyridamole. Treatment efficacy was evaluated after 15 days and salvage treatments were also considered for non-responders. Upon disease remission, the patients already treated with antiplatelet agents received ticlopidine for one year.\n Regarding the treatment of acute phase TTP, similar overall response rates were observed in the two groups (91.4% in group B vs. 75.6% in group A), but lower mortality rates were observed at 15 days in the patients treated with antiplatelet agents; as a matter of fact, 5 patients from arm A died in the first 15 days (13.5%) versus only one in arm B (2.8%). These figures, while not statistically significant, seem to suggest that antiplatelet agents might be useful in preventing deaths in acute TTP; moreover, bleeding did not worsen in antiplatelet agent-treated patients. As for the role of maintenance treatment, our results support the efficacy and safety of one-year ticlopidine therapy since the current relapse rate is significantly higher in non-treated patients; as a matter of fact, 6 patients (21.4%) in the non-ticlopidine group and only 2 (6.25%) in the ticlopidine group relapsed (P = .0182 in favor of maintenance treatment).\n Our results suggest the usefulness of antiplatelet agents in the treatment of acute phase TTP patients. Moreover, one-year ticlopidine maintenance therapy appears to be beneficial in preventing TTP relapses; however, only the completion of an adequate follow-up for all patients will definitively confirm this observation.", "In thrombotic microangiopathies hemolytic uremic syndrome and thrombocytopenic purpura, plasma exchange (PE) therapy using fresh frozen plasma is standard. In almost 20% of the patients, however, this approach is ineffective. This prospective, randomized study for the treatment of patients with thrombotic microangiopathies (PRODROMI) compares PE with fresh frozen plasma (A) and cryosupernatant (B). The participating centers were the University Clinics of Freiburg, Hamburg, Düsseldorf, Essen, Göttingen, Mannheim, Ulm, Jena, Tübingen, Würzburg, Kreiskrankenhaus Offenburg, Städt Klinikum Karlsruhe, and Horst-Schmidt Kliniken in Wiesbaden, Germany. Patients (18 to 80 years) were diagnosed by the individual centers based on clinical and laboratory findings (thrombocyte/fragmentocyte count, hemoglobin, serum creatinine, haptoglobin and lactate dehydrogenase levels; negative Coombs-test is obligatory). HIV infection, bone marrow, or solid organ transplantation were exclusion criteria. After written consent, patients were randomized in the A or B group. All patients received 1.5 mg/kg methylprednisolone as a basic therapy. The first PE always was performed with fresh frozen plasma (50 ml/kg). A minimum of 5 and a maximum of 10 PEs were required. Thrombocyte count above 150,000/microl was considered to be a successful therapy. Treatment failure was defined as not responding to 10 PE with a thrombocyte count above 150,000/microl or a fall below this value within 30 days after stopping PE. Patients with clinical and laboratory signs of thrombotic microangiopathy occurring later than 30 days after having stopped PE were considered to have a relapse. Primary endpoints were survival, intensity of required PE sessions (duration, volume, and number), and relapse rate. Follow-up of clinical outcome was 2 years; von Willebrand Factor (vWF), vWF-cleaving-protease activity, and Factor H were determined.", "nan", "A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1.1-3.95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.", "Seventy-nine children with haemolytic uraemic syndrome (mean age 28 months) were randomly assigned either to a group receiving plasma infusions (plasma group, n = 39) or to a group treated conservatively (control group, n = 40). The duration of haemolysis, thrombocytopenia and anuria was similar in the two groups. Serum creatinine levels were similar in the two groups at the 1-month follow-up but were higher in the control group at 3 months (plasma group 49 +/- 14, control group 66 +/- 28 mumol/l; P less than 0.02) and at 6 months (plasma group 48 +/- 13, control group 63 +/- 21 mumol/l; P less than 0.005). The prevalence of proteinuria was also higher in the control group at the 6-month follow-up (plasma group 17%, control group 46%; P less than 0.02). However, differences were no longer significant after 1 year. Renal tissue was examined in 54 cases (plasma group, n = 27; control group, n = 27). Diffuse cortical necrosis was present in 7 cases in the control group but was absent in the plasma group (P less than 0.02). Taking into consideration the higher serum creatinine levels, the higher prevalence of proteinuria during the first 6 months of follow-up in the control group and the presence of diffuse cortical necrosis in this group compared with the plasma group, we conclude that plasma infusions should be regarded as beneficial. Further study is needed to determine which plasma fraction is involved.", "From 1976 to 1985, a total of 58 infants and children with the hemolytic-uremic syndrome were randomly assigned to treatment either with heparin and dipyridamole or with supportive management only. In the treatment group, two patients died in the early weeks of the disease. Analysis of clinical and laboratory data showed no significant difference between either group of patients as to the evolution of their illness except for a significantly higher incidence of anuria and a significantly faster recovery from hypertension in the treated group. Renal biopsy studies showed no differences between the two groups in terms of incidence and severity of the histologic lesions. The long-term data on blood pressure and creatinine clearance values in the survivors were similar in both groups. This study indicates that treatment with heparin and dipyridamole has no benefit over symptomatic therapy alone in the typical form of childhood hemolytic-uremic syndrome.", "Diarrhea-associated hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. Most cases are caused by an intestinal infection with Shiga toxin-producing strains of Escherichia coli.\n To determine if administration of an oral agent that binds Shiga toxin could diminish the severity of diarrhea-associated HUS in pediatric patients.\n Multicenter, randomized, double-blind, placebo-controlled clinical trial of 145 children (96 experimental and 49 placebo) aged 6 months to 18 years with diarrhea-associated HUS conducted between July 27, 1997, and April 14, 2001, at 26 tertiary care pediatric nephrology centers in the United States and Canada. Trial included 2 phases, the hospital course for treatment of the acute illness and a 60-day outpatient follow-up period after discharge from the hospital.\n Patients were assigned to receive the binding agent, 500 mg/kg daily, or cornmeal placebo orally for 7 days in a 2:1 randomization scheme.\n Combined frequency of death or serious extrarenal events and need for dialysis in the experimental vs placebo group.\n A total of 62 patients (43%) were male and 123 (85%) were white. The median age of the patients was 4.2 years. Most patients (59%) were transferred from other hospitals to participating sites. The severity of disease at the time of randomization was comparable in the 2 groups. The prevalence of death or serious extrarenal events was 18% and 20% in the experimental and placebo groups, respectively (P =.82). Dialysis was required in 42% of experimental and 39% of placebo groups (P =.86).\n Oral therapy with a Shiga toxin-binding agent failed to diminish the severity of disease in pediatric patients with diarrhea-associated HUS.", "Thrombotic thrombocytopenic purpura is an uncommon disease with a high mortality rate even with current treatment. The cause of the syndrome and its optimal treatment are unknown. Although both plasma exchange and plasma infusion have been useful treatments, it is not clear which is superior. In this report we describe a prospective randomized trial comparing plasma exchange with plasma infusion for the treatment of thrombotic thrombocytopenic purpura.\n One hundred two patients with thrombotic thrombocytopenic purpura were randomly assigned to receive either plasma exchange or plasma infusion with fresh-frozen plasma on seven of the first nine days after entry into the trial. The total volume of plasma received by patients undergoing plasma exchange was three times that received by patients undergoing plasma infusion. All the patients also received aspirin and dipyridamole. The outcomes in the two groups were compared at the end of the first treatment cycle (day 9) and after six months.\n At the end of the first treatment cycle patients receiving plasma exchange had a higher rate of response as defined by an increase in the platelet count (24 of 51 patients) than those who received plasma infusion (13 of 51, P = 0.025). Of the 51 patients treated with plasma exchange, 2 died, whereas 8 of the 51 patients who received plasma infusion died (P = 0.035). After six months the outcome in the plasma-exchange group was still superior, with a response observed in 40 of 51 patients, whereas 25 of 51 patients in the plasma-infusion group responded (P = 0.002). Eleven patients in the plasma-exchange group died, as did 19 patients in the plasma-infusion group (P = 0.036). The overall mortality was 29 percent.\n Plasma exchange is more effective than plasma infusion in the treatment of thrombotic thrombocytopenic purpura.", "To determine whether steroids could be of clinical benefit in the treatment of the hemolytic uremic syndrome (HUS), we conducted a randomized, double-blinded, placebo-controlled trial of methylprednisone (5 mg/kg per day in four oral doses over 7 days), in children with HUS during the acute phase. Ninety-two patients with typical HUS (47 receiving placebo and 45 receiving steroids) were investigated for neurological, hematological, and nephrological variables. There were no differences between groups in the number of convulsive episodes or transfusion requirements during the hospital stay. Serum creatinine levels were slightly increased on day 10 in the placebo group compared with the steroid group (P = 0.06) and declined significantly between days 1 and 10 only in the steroid group (P = 0.001). In the 51 patients with anuria (24 placebo, 27 steroids), median serum creatinine levels were reduced in the steroid group compared with the placebo group on the 10th day (P = 0.01). Differences in median days of oliguria [11.5 versus 8 (P = 0.28)], anuria [5 versus 7 (P = 0.20)], and dialysis [12 versus 10 (P = 0.26)] for the placebo and the steroid group respectively were not significant. Our data suggest that oral steroids are not able to modify hematological, neurological, or nephrological clinical parameters during the acute phase of childhood HUS, even though they do seem to be associated with a more rapid decline in serum creatinine levels.", "Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease that is treated with plasma exchange and typically with replacement with fresh frozen plasma (FFP). This approach results in an approximate 50% response rate following 1 week of therapy and 80% survival. Cryoprecipitate poor plasma (CPP) is plasma from which the cryoprecipitate fraction is removed. CPP has been reported to be successful as salvage therapy in refractory TTP and has been suggested to be superior to FFP in retrospective studies. The present report compares initial therapy of TTP with exchange using replacement with either FFP or CPP in a multi-institutional prospective randomized study performed by the North American TTP Group (NATG Group) from 1993 to 1995. Initial therapy also included corticosteroids. Antiplatelet drugs or vinca alkaloids were not employed. A severity score index, response score, and individual clinical parameters (platelet count, LDH x upper limit of normal, hemoglobin level, and creatinine) were compared at their nadir or peak values, baseline, and days +6 and +13 of therapy. Thirteen patients were randomized to FFP exchange and 14 to CPP exchange. Results were equivalent for all parameters. Survival was equal with three deaths in each group. These data indicate that the efficacy of FFP and CPP are the same in the initial treatment of TTP in adults.", "The results of a controlled therapeutic trial comparing 2 groups of patients presenting with hemolytic-uremic syndrome (HUS) are reported. Group A (15 children) was given urokinase (UK) and heparin; group B (18 children) received no treatment. Ages of patients, the delay before admission, the severity of anemia, thrombocytopenia and initial renal failure were similar in both groups. UK was responsible for bleedings in 12 children, minimal in 8, severe in 4. No child died in group A, 3 children died in group B (n.s.). Durations of hemolysis, thrombocytopenia and anuria were similar in both groups. Long-term evolutions of renal function and arterial pressure were comparable in both groups. Needle kidney biopsy (26 cases) showed cortical necrosis in 3 children of group A and in 2 of group B, and glomerular thrombotic microangiopathy in 10 children of group A and in 11 of group B. The average ratio of injured glomeruli was 40 (19 to 80) in group A, and 38 (21 to 75) in group B. Two children in group A and 3 children in group B presented with 50 to 80% of glomerular lesions. This trial suggests that UK is of no significant value in the treatment of HUS." ]

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[ "Health services utilization with reference drug pricing of histamine(2) receptor antagonists in British Columbia elderly.", "The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs.", "Cardiovascular outcomes after a change in prescription policy for clopidogrel.", "Cost analysis of a provincial drug program to guide the treatment of upper gastrointestinal disorders.", "Effects of an evidence report and policies lifting reimbursement restrictions for acid suppressants: analysis of the Belgian national database.", "Effects of a prior-authorization policy for celecoxib on medical service and prescription drug use in a managed care Medicaid population.", "An evaluation of Oregon's evidence-based Practitioner-Managed Prescription Drug Plan.", "Plan-sponsor savings and member experience with point-of-service prescription step therapy.", "Retrospective assessment of Medicaid step-therapy prior authorization policy for atypical antipsychotic medications.", "Medicaid prior-authorization programs and the use of cyclooxygenase-2 inhibitors.", "Impact of Medicaid prior authorization on angiotensin-receptor blockers: can policy promote rational prescribing?", "The effects of mandatory prescribing of thiazides for newly treated, uncomplicated hypertension: interrupted time-series analysis.", "Impact of a criteria-based reimbursement policy on the use of respiratory drugs delivered by nebulizer and health care services utilization in Nova Scotia, Canada.", "Effect of a prior-authorization requirement on the use of nonsteroidal antiinflammatory drugs by Medicaid patients.", "Clinical and financial outcomes associated with a proton pump inhibitor prior-authorization program in a Medicaid population.", "Guidelines accompanied by changes in reimbursement rules. Effects on lipid-lowering drug prescribing.", "Impact of a limited fluoroquinolone reimbursement policy on antimicrobial prescription claims.", "Impact of administrative restrictions on antibiotic use and expenditure in Ontario: time series analysis.", "The effects of coxib formulary restrictions on analgesic use and cost: regional evidence from Canada.", "Antiulcer prescribing program in a state correctional system.", "Evaluation of an automated system for prior authorization: a COX-2 inhibitor example.", "Differential effect of early or late implementation of prior authorization policies on the use of Cox II inhibitors.", "Use of atypical antipsychotic drugs for schizophrenia in Maine Medicaid following a policy change.", "Switching statins in Norway after new reimbursement policy: a nationwide prescription study.", "A therapeutic substitution policy for proton pump inhibitors: clinical and economic consequences.", "Medicaid prior authorization and controlled-release oxycodone.", "Effect of prior authorization of second-generation antipsychotic agents on pharmacy utilization and reimbursements." ]

[ "In October 1995, British Columbia introduced a reference pricing policy for five therapeutic classes of drugs, including histamine(2) receptor antagonists (H(2)RAs), for beneficiaries of its prescription drug program, Pharmacare.\n To evaluate utilization trends in consumption of health services in a cohort of Pharmacare beneficiaries to determine if a worsening of health outcomes could be detected after implementation of the reference pricing policy.\n Two cohorts, \"control\" (21 months before the reference pricing policy) and \"exposed\" (at risk for policy effects), were followed for 21 months. Using a longitudinal generalized linear model (Poisson), and controlling for age, sex, and prescriptions in unique drug classes, trend lines in each of these time series were compared for 3 periods: 9 months before policy implementation (or corresponding index date in the control cohort), 6 months after policy implementation, and a subsequent 6-month period.\n Two cohorts, each of size 10,000, were constructed by randomly sampling the population of Pharmacare beneficiaries exposed to H(2)RAs and other antisecretory drugs for 1993 through 1996.\n Prescriptions, physician office visits and associated transactions (ie, laboratory tests), emergency room visits, hospitalizations, hospital length of stay, and vital statistics.\n Differences between periods and between cohorts for health services utilization were not significant or decreased after imposition of the reference pricing policy.\n For these measures, there has been no worsening of health outcomes associated with implementing the reference pricing policy.", "To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs.\n Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001.\n RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes.\n After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP.\n Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated.", "Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction.\n We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding.\n The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change.\n The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.\n 2008 Massachusetts Medical Society", "Concerned with the rising costs of its drug programs for seniors and social-assistance recipients, the government of Newfoundland and Labrador requested physicians and pharmacists at the Memorial University of Newfoundland, and members of the Newfoundland and Labrador Medical Association and the Newfoundland Pharmaceutical Association to provide guidance to the health care community for the use of drugs to treat upper gastrointestinal disorders.\n Algorithms for the management of dyspepsia and gastrointestinal reflux disease were created and distributed to all physicians and pharmacists in the province in June 1996. On July 1, 1996, the provincial government implemented a program to restrict payment for proton-pump inhibitors through its drug programs to situations defined by the algorithms. Restrictions were not applied to the prescribing of cimetidine, ranitidine and prokinetic agents. The status of famotidine and nizatidine was changed from \"open benefit\" to \"special consideration,\" which requires prescribers to request authorization of their use on a case-by-case basis.\n Between July 1 and Dec. 31, 1996, 973 of 1078 requests for a proton-pump inhibitor were approved (679 for gastroesophageal reflux, 186 for Helicobacter pylori eradication, 55 for ulcer treatment and 53 for other reasons). The program resulted in a sustained reduction in drug expenditures. Total drug expenditures, which had risen from $39.0 million in 1992/93 to $50.8 million in 1995/96, fell after implementation of the program to $46.4 million in 1996/97 because of a decrease of more than 80% in the use of proton-pump inhibitors. Expenditures on proton-pump inhibitors, which had increased from $0.7 million for the 6 months ending March 1993 to $1.6 million for the 6 months ending March 1996, decreased to $0.3 million for the 6 months ending March 1997. The use of H2-antagonists, but not prokinetic agents, increased concomitantly with the decline in proton-pump inhibitor use. Compared with the year preceding implementation of the program, annual combined expenditures in the subsequent 3 years for H2-antagonists, prokinetic drugs and proton-pump inhibitors were reduced by $1.6 million, $1.7 million and $1.0 million, respectively. Feedback from physicians and pharmacists was supportive for the clinical information and prescribing guidelines. Concerns were mostly limited to process issues.\n The program, designed by health care professionals, approved by health care associations and implemented by the province of Newfoundland and Labrador to guide the treatment of upper gastrointestinal disorders, has achieved a substantial reduction in drug expenditures.", "To explore the effect on prescribing of policies that lift reimbursement restrictions on selected H2-antihistamines and proton pump inhibitors (PPI) and of practice recommendations.\n Monthly claims based data for proton pump inhibitors (PPIs) and H2-antihistamines were obtained from the national health insurance database (Farmanet 1997-2005). Two policies were issued. In March 2001 two H2-antihistamines and in March 2003 two PPIs became available without restrictions. An evidence report was distributed in September 2004. Periods before and after implementation of the interventions were compared. Interrupted time series with segmented regression analysis was used to assess and compare time trends.\n The first policy resulted in an increase of volume (1.6 million DDDs; 95% CI 1.4-1.8 million; p < .001) and expenditure (euro 637,744; 95% CI 177 052-1 098 437; p = .026) for H2-antihistamines, but consumption of PPIs continued to grow. After the second policy use of selected PPIs also increased (4.7 million DDDs increase; 95% CI 3.9-5.5 million; p < .001), but more than the desired shift toward selected PPIs. Although total expenditure stabilized at a lower level, there was no significant change of trend. Publication of the evidence report did not have any impact on prescribing.\n Policies that lift reimbursement restrictions did not result in meaningful changes in utilization or cost saving. They may even have unintended effects. Collaboration between policymakers and guideline developers and linking policies to evidence-based guidelines could be a more effective way to pursue cost-containment and better quality of care.\n Copyright (c) 2008 John Wiley & Sons, Ltd.", "Prior authorization (PA) is a poorly studied but commonly employed policy used by health care payers to manage the rising costs of pharmacy benefits.\n The aim of this study was to evaluate the intended and unintended effects of a PA policy for celecoxib on pharmacy and medical-service utilization in a Medicaid managed-care organization.\n This was a retrospective, interrupted time-series analysis of 22 monthly health-related utilization rates from January 1, 1999, to October 31, 2000. All Medicaid claims for CareOregon (a managed-care organization) and a fee-for-service program were reviewed. A model was constructed to evaluate changes in utilization of therapeutically related drug classes (eg, conventional nonsteroidal anti-inflammatory drugs [NSAIDs], gastrointestinal agents), office and emergency-department encounters, and hospitalizations before and after the PA policy was implemented on November 16, 1999. A secondary analysis evaluated these changes among a sample of prior NSAID users.\n After the PA policy was implemented, use of celecoxib was immediately reduced from 1.07 to 0.53 days' supply per person-year (58.9%; 95% CI, 50.0%-67.9%). The monthly rate of increase was also reduced (P < 0.001). Utilization changes were not observed in other drug classes. Similar changes were observed in the secondary analysis. An 18% (95% CI, 2.2%-33.9%) nonsignificant increase in emergency-department visits was observed in the entire sample after the PA policy was implemented. However, a similar change was not observed in the secondary analysis of prior NSAID users. No other changes in medical service encounters were noted after the PA policy was activated.\n This observational study found that celecoxib use was substantially reduced after the implementation of a PA policy. No important changes in use of other drug classes were detected. The overall increase in emergency-department visits--although not observed among previous NSAID users--should be explored on the individual level.", "This paper describes Oregon's implementation of its publicly developed, evidence-based, Practitioner-Managed Prescription Drug Plan (PMPDP). Oregon's PMPDP was initially self-enforced with a dispense as written (DAW) exception process, followed by an educational prior authorization (soft PA) method, and finally no active enforcement. Market-share trends indicate that the educational prior authorization process was most effective at increasing the use of preferred agents. Pharmacy costs decreased 9.1 percent and 17.7 percent after implementation of the DAW and soft PA policies, respectively. Data from nonenforced PMPDP classes showed no change; this suggests the need for effective methods to encourage PMPDP compliance.", "To examine the effect of prescription step-therapy programs in terms of plan-sponsor savings and member experience at the point of service.\n Plan-sponsor savings were measured using a quasi-experimental, case-control design. Member experience with step therapy was measured using a self-administered mailed survey.\n A 20,000-member plan implemented 3 step therapy programs in September 2002: proton pump inhibitors, selective serotonin reuptake inhibitors, and nonsteroidal anti-inflammatory drugs. Pharmacy claims from September 1, 2001, through June 30, 2003, were examined to compare changes in per-member-per-month (PMPM) net cost between the intervention group and a random sample of members from commercial plans without the step therapy programs. A mailed, self-administered survey was sent to members with a step edit from September 1, 2002 to December 31, 2002.\n The employer experienced a decrease of 0.83 dollars in net cost after implementing step therapy, while the comparison group had an upward trend of 0.10 dollars PMPM for these therapy classes. Member-reported outcomes indicated that approximately 30% of patients received a generic, 23% were granted a medical exception for the brand, 17% received no medication, and 16% paid the full retail price for the brand. If the pharmacist vs the patient contacted the physician, members were 8 times more likely to receive a medication covered by the health plan (OR, 8.10; 95% CI, 2.94-22.33 vs OR, 8.23; 95% CI, 3.11-21.93). Compared with those who received first-line therapy, those who paid out of pocket for the brand medication vs those who did not receive any medication were less likely to be satisfied with their pharmacy benefit (OR, 0.25; 95% CI, 0.08-0.80 vs OR, 0.12; 95% CI, 0.04-0.41).\n Step therapy produces significant drug savings. However, there appear to be opportunities to further members' and providers' understanding of these programs.", "Antipsychotic medications account for more prescription expenditures in Medicaid than any other therapeutic category. This has made them an attractive target for states hoping to curtail rising expenditures.\n The objective of this study was to document the effects of a step-therapy prior authorization (PA) policy for atypical antipsychotic medications on: (1) Medicaid prescription expenditures among all Medicaid beneficiaries and (2) prescription and health service expenditures among patients with schizophrenia.\n Prescription, inpatient, outpatient, and long-term care State Medicaid Research Files from Georgia and Mississippi from January 1, 1996, to December 31, 1997, were used to model an interrupted time-series analysis. We compared a step-therapy PA policy implemented in Georgia to a nonequivalent/no-treatment control group (Mississippi) over 10-month prepolicy, 11-month policy, and 3-month postpolicy periods. Segmented regression was used to estimate antipsychotic prescription expenditures among all eligible Medicaid beneficiaries. We used generalized estimating equations to model prescription and other health service expenditures with difference-indifference regressions among a cohort of patients with schizophrenia.\n Compared with Mississippi, Georgia saved approximately USD 7 million in atypical antipsychotic expenditures over the 11-month policy period. Among patients with schizophrenia, the PA policy was associated with a USD 19.62 per member per month (PMPM) decrease in atypical antipsychotic expenditures and a USD 2.20 PMPM increase in typical antipsychotic expenditures (both, P < 0.001). Among the same patients with schizophrenia however, the reduction in atypical antipsychotic expenditures was accompanied by a USD 31.59 PMPM increase in expenditures for outpatient services (P < 0.001).\n Although PA of atypical antipsychotics was associated with significant prescription savings to the Georgia Medicaid program, among a vulnerable cohort of patients with schizophrenia, an increase in outpatient expenditures was associated with overall savings.", "Over the past five years, selective cyclooxygenase-2 inhibitors (coxibs) have accounted for a growing proportion of prescriptions for nonsteroidal antiinflammatory drugs (NSAIDs). To control these expenses, many state Medicaid programs have implemented prior-authorization requirements before coxibs can be prescribed. We evaluated the effect of such programs on the use of coxibs by Medicaid beneficiaries.\n We surveyed state Medicaid agencies to determine whether prescription of coxibs required prior authorization and, if so, the criteria for authorization. For each program, we compared these criteria with evidence-based recommendations for prescribing of coxibs. Using data for all filled prescriptions in 50 state Medicaid programs from 1999 through the end of 2003, we calculated the proportion of defined daily doses of NSAIDs accounted for by coxibs. Time-series analyses were used to measure the changes in prescription patterns after the implementation of each prior-authorization program.\n By 2001, coxibs accounted for half of all NSAID doses covered by Medicaid. This proportion varied widely according to the state in 2003, from a low of 11 percent to a high of 70 percent of all NSAID doses. Twenty-two states implemented prior-authorization programs for coxibs during the study period. Overall, the implementation of such programs reduced the proportion of NSAID doses made up by coxibs by 15.0 percent (95 percent confidence interval, 10.9 to 19.2 percent), corresponding to a decrease of 10.28 dollars (95 percent confidence interval, 7.56 dollars to 13.00 dollars) in spending per NSAID prescription. The effect of such programs was not influenced by the degree to which a prior-authorization program incorporated evidence-based prescribing recommendations.\n The use of coxibs and spending on NSAIDs varies widely by state and declined substantially after the implementation of prior-authorization programs. Determining whether these reductions are clinically appropriate will have important implications for the development of rational drug-reimbursement policies.\n Copyright 2004 Massachusetts Medical Society.", "Prescription drug cost containment is a key health policy priority. State Medicaid programs have implemented policies requiring prior authorization before paying for angiotensin-receptor blockers (ARBs), a costly class of blood pressure medications. We examined the impact of these policies on drug use. We found that policies using a stepped-therapy approach reduced ARB use by 1.6 percent when first implemented and decreased the subsequent trend in ARB use by 1.3 percent per quarter; alternative approaches were unsuccessful. These findings have important implications for the development of rational drug reimbursement policy under Medicare Part D and other health insurance plans.", "The purpose of our study was to evaluate the effects of a new reimbursement rule for antihypertensive medication that made thiazides mandatory first-line drugs for newly treated, uncomplicated hypertension. The objective of the new regulation was to reduce drug expenditures.\n We conducted an interrupted time-series analysis on prescribing data before and after the new reimbursement rule for antihypertensive medication was put into effect. All patients started on antihypertensive medication in 61 general practices in Norway were included in the analysis. The new rule was put forward by the Ministry of Health and was approved by parliament. Adherence to the rule was monitored only minimally, and there were no penalties for non-adherence. Our primary outcome was the proportion of thiazide prescriptions among all prescriptions made for persons started on antihypertensive medication. Secondary outcomes included the proportion of patients who, within 4 mo, reached recommended blood-pressure goals and the proportion of patients who, within 4 mo, were not started on a second antihypertensive drug. We also compared drug costs before and after the intervention. During the baseline period, 10% of patients started on antihypertensive medication were given a thiazide prescription. This proportion rose steadily during the transition period, after which it remained stable at 25%. For other outcomes, no statistically significant differences were demonstrated. Achievement of treatment goals was slightly higher (56.6% versus 58.4%) after the new rule was introduced, and the prescribing of a second drug was slightly lower (24.0% versus 21.8%). Drug costs were reduced by an estimated Norwegian kroner 4.8 million (0.58 million Euros, US$0.72 million) in the first year, which is equivalent to Norwegian kroner 1.06 per inhabitant (0.13 Euros, US$0.16).\n Prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a reimbursement rule requiring the use of thiazides as the first-choice therapy was put into effect. However, the resulting savings on drug expenditures were modest. There were no significant changes in the achievement of treatment goals or in the prescribing of a second antihypertensive drug.", "In February 2000, the Nova Scotia Seniors' Pharmacare Program announced a change in the reimbursement of respiratory drugs that added specific reimbursement criteria for wet nebulization therapy. Policy implementation coincided with multifaceted interventions to assist patients and providers with the change.\n To assess the impact of the new policy and associated interventions on the use of wet nebulization and portable inhaler delivery systems of respiratory drugs and on the utilization of health services.\n The administrative claims database identified all beneficiaries (age > or = 65 yrs) who received at least one respiratory drug prescription in the 12 months before the study. These patients were then grouped into the wet nebulization cohort or the control cohort receiving a metered-dose or a dry-powder inhaler. The study period was from April 1998-February 2002. Use of respiratory drugs, physician visits, and hospitalizations were compared between study cohorts using an interrupted time-series design.\n A sharp decrease was noted in use of wet nebulization after the policy announcement, along with an increase in use of short-acting beta2-agonists and anticholinergic agents delivered by metered-dose or drypowder inhaler. From December 1999 to December 2001, in the heavy wet nebulization cohort (a subset of the wet nebulization cohort), wet nebulization use dropped from 100% to 35%; in the wet nebulization cohort, wet nebulization use decreased from 67% to 20%. Rates of spacer device use were 42%, 31%, and 17% in the heavy wet nebulization, wet nebulization, and control cohorts, respectively, in December 2001. Rates of general practitioner visits and hospitalizations for respiratory conditions did not increase in the intervention cohorts after the policy announcement. In fact, relative to the control cohort, health services use in response to the policy and interventions in the wet nebulization cohort decreased.\n The reimbursement policy resulted in decreased use of respiratory drugs delivered by wet nebulization without a negative impact on general practitioner visits and hospitalizations for respiratory conditions.", "Prior authorization--mandatory advance approval for the use of expensive medications--is now the primary method by which Medicaid programs control expenditures for drugs. However, whether this policy reduces expenditures for specific drugs without causing the unwanted substitution of other drugs or medical services has been largely unstudied. We evaluated the effects of a prior-authorization policy involving nongeneric nonsteroidal antiinflammatory drugs (NSAIDs) in the Medicaid program in Tennessee.\n We compared monthly Medicaid expenditures that were potentially affected by the policy change during the year before and the two years after its implementation. We studied prescriptions for NSAIDs, other analgesic or antiinflammatory drugs, and psychotropic drugs, as well as outpatient services and inpatient admissions for the management of pain or inflammation.\n At the midpoint of the base-line year, 495,821 people were enrolled in Medicaid. During that year, mean annualized Medicaid expenditures for NSAID prescriptions amounted to $22.41. Expenditures decreased by 53 percent (95 percent confidence interval, 48 to 57 percent) during the next two years, for an estimated savings of $12.8 million. The reduction in expenditures resulted from the increased use of generic NSAIDs, as well as from a 19 percent decrease in overall NSAID use (95 percent confidence interval, 13 to 25 percent). There was no concomitant increase in Medicaid expenditures for other medical care. Regular users of nongeneric NSAIDs, those most affected by the policy change, had similar reductions in NSAID expenditures and use, with no increase in expenditures for other medical care.\n Prior-authorization requirements may be highly cost effective with regard to expenditures for NSAIDs, drugs that have very similar efficacy and safety but substantial variation in cost.", "To examine the clinical and financial outcomes associated with a proton pump inhibitor (PPI) prior-authorization policy.\n Interrupted time-series analyses of antisecretory prescription drug claims. Separate 6-month retrospective cohort analyses were conducted to estimate the clinical and financial effects of the policy.\n More than 1.2 million Medicaid enrollees, with subgroup analyses of 5965 continuously eligible, potential antisecretory medication users. Measures included antisecretory drug expenditures, proportions of patients with at least 1 gastrointestinal diagnosis and gastrointestinal-related ambulatory and inpatient medical service visit, and subsequent gastrointestinal-related and total medical service expenditures.\n There was a 90.9% decrease in PPI per-member-per-month expenditures and a 223.2% increase in histamine2-receptor antagonist (H2A) per-member-per-month expenditures in the month immediately following the implementation of the policy (P < .001 for both). A greater proportion (80.7%) of prior-authorization eligible enrollees who received a PPI had at least 1 diagnosis for a gastrointestinal condition than enrollees who received an H2A (64.1%) or no antisecretory drugs (48.4%) (P < .001 for both). Two-part, finite mixture regression analyses indicated that the enrollees who received an H2A or no antisecretory drugs were no more likely to have incurred greater total medical care expenditures than enrollees who received a PPI.\n Prior authorization for PPIs had the effect of reducing use of high-cost PPIs, while encouraging use of lower costing H2As without evidence of adverse medical consequences.", "To analyse the effect of guidelines accompanied by changes in reimbursement rules for the prescription of lipid-lowering drugs (LLDs).\n Observational study focusing on LLD use before (1994-98) and after an intervention (1999).\n Guidelines were developed by the Danish College of General Practitioners and focused on prevention of cardiovascular heart disease (CHD). Guidelines were sent out and changes in reimbursement took place in December 1998. Prescriptions for LLDs were extracted from a population-based prescription database (Odense University Pharmacoepidemiological Database, OPED) covering 10% of the Danish population (470,000 inhabitants).\n Incidence rate and 1 year prevalence rate (annual prevalence) of LLD use.\n The incidence of LLD use increased significantly in the year following the intervention. Incidence rate ratio (after/before) was 1.43 (CI 1.35-1.52). The annual prevalence of LLD use in the population increased by 0.4% after the intervention (0.2% before). The corresponding figure for patients with diabetes mellitus (treated with insulin or oral anti-diabetics) was 2.3% after the intervention (1.2% before), and for patients with CHD (treated with vasodilators) 8.1% after the intervention (5.0% before).\n Guidelines accompanied by a change in reimbursement rules had a significant influence on the prescribing of lipid-lowering drugs.", "To examine the influence on administrative pharmacy claims of a policy that limited the reimbursement of the fluoroquinolones and other antimicrobials in the senior population within Nova Scotia, Canada.\n The administrative claims database of the Nova Scotia Seniors' Pharmacare Program was used to identify all prescription claims for orally administered antibiotics and urinary antiinfectives. The number of beneficiaries receiving antimicrobials and the number, duration, and cost of prescriptions for antimicrobials were measured monthly. Descriptive time-series plots were used to compare antimicrobial use for two 12-month periods before the institution of the policy (December 1, 1994-November 30, 1995, and December 1, 1995-November 30, 1996) and the 12 months after the policy took effect (January 1, 1997-December 31, 1997).\n Following the implementation of the fluoroquinolone reimbursement policy, the number of patients using antimicrobials decreased by 2.2% and the number of prescriptions for antimicrobials decreased by 3.4%. Fluoroquinolone prescriptions decreased by 80.2%; prescriptions for sulfonamides and trimethoprim increased by 34.9%, cephalosporins by 17.0%, and macrolides and lincosamides by 16.5%. The only prescription duration to change was the fluoroquinolones, which increased by 25%. The average cost per antimicrobial user/year decreased from $35.24 during prepolicy period 2 to $27.51 during the postpolicy period.\n Prescription claims for fluoroquinolones in seniors decreased following the introduction of the policy. Total antimicrobial use also decreased, although this may be related to other factors. The effect of this policy change on patient outcomes requires further study.", "In a potential attempt to guide antibiotic prescribing based on current clinical evidence and mitigate the spread of antibiotic resistance, in March 2001 the Ontario Drug Benefit programme restricted reimbursement of two fluoroquinolone antibiotics--ciprofloxacin and ofloxacin--to its beneficiaries. Our objective was to determine the impact of this policy on the volume and cost of antibiotic prescribing.\n Weekly administrative data on antibiotic prescribing volumes and expenditures were analysed between January 1999 and September 2002 to estimate the effect of the policy changes using time series analysis.\n The policy changes were associated with a statistically significant shift downwards for the fluoroquinolones as a category (1905 fewer prescriptions each week, representing a saving of Can$105,707 a week), driven by a decrease in prescriptions for ciprofloxacin (2084 fewer prescriptions a week, saving Can$129,421 a week). Nitrofurantoin (200 more prescriptions a week, costing an extra Can$2082 a week) and trimethoprim-sulphamethoxazole (532 more prescriptions a week, costing an extra Can$1473 a week) demonstrated a statistically significant shift upwards. The latter also showed a decrease in trend and nitrofurantoin an increase in trend during the time period. There was no statistically significant change in either the total number of antibiotic prescriptions or expenditures associated with the policy of limiting their use.\n Although no direct cause and effect can be shown with these observational data, the results suggest that the change in reimbursement policy to restrict prescribing of fluoroquinolones decreased their use and associated expenditures. These decreases were offset by increases in the use of other antibiotics. The balance of consequent benefit and harm of these shifts in prescribing patterns needs to be examined carefully. Alternative solutions to encourage appropriate use of antibiotics deserve exploration.", "Public insurance plans for pharmaceuticals in Canada differ substantially across provinces in the conditions under which pharmaceuticals are reimbursed. Coxibs provide a good example. Québec had no restrictions on reimbursement for these drugs. Ontario required physicians to submit the clinical indications for their use on the prescription. British Columbia required physicians to seek and receive prior authorisation from the drug plan.\n This study compares the effects of different reimbursement policies on coxib, non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs), and gastro-protective agent (GPA) use and cost.\n Analysis of retrospective time series analysis of all NSAID and GPA administrative claims data from April 1997 through December 2002.\n Administrative claims data from April 1997 through December 2002 for each of the publicly funded drug plans in Québec, Ontario, and British Columbia. In addition, we obtained data from BC PharmaNet, which records all dispensed prescriptions in British Columbia.\n Senior beneficiaries (>or= 65 years).\n We compared the projected total NSAID utilisation in the absence of coxib reimbursement restriction with actual utilisation by province and drug category. Projected utilisation was based on ARIMA modelling and reported as the number of defined daily doses (DDDs) per 100 senior (>or=65 years) beneficiaries/month.\n In Ontario, under its \"limited use\" policy, uptake and steady-state use of coxibs was similar to that in Québec, where there were no restrictions. In British Columbia, publicly funded use of coxibs was 6% of that in Ontario and Québec. Despite a shift to private reimbursement, total coxib use in BC was only 50% of use in Ontario and Québec. The use of all NSAIDS (nsNSAIDS plus coxibs) increased for all provincial drug plans except for BC. The increase and overall rate of total NSAID use was greatest in Ontario. Neither Ontario's nor BC's policies had an impact on use of nsNSAIDs or GPAs.\n Only BC's policy effectively limited publicly funded coxib use. However, there was substantial cost-shifting to out-of-pocket and third party insurance plans in BC.", "To describe a formulary antiulcer agent prescribing program developed as the result of a drug use evaluation (DUE). Program implementation, methods, cost impact, and results of a follow-up DUE are provided.\n The institution is a 51,000-bed correctional system consisting of 40 separate units each containing an ambulatory care clinic. Medication orders are transmitted via mainframe computer system to one of four pharmacies, which collectively dispense an average of 4000 medication orders (30 days' supply) per day.\n Results from the antiulcer agent (cimetidine, ranitidine, sucralfate) DUE revealed that the agents studied were prescribed in dosages and durations exceeding criteria developed by the Pharmacy and Therapeutics Committee. A program designed to reduce dosages to maintenance therapy after eight weeks at treatment dosage was developed by the Pharmacy and Therapeutics Committee with staff physician input. Antiulcer agent use and expenditures were followed and a follow-up DUE was completed seven months after program implementation. Antacid use and frequency of upper gastrointestinal studies that were ordered were followed.\n The follow-up DUE showed the mean daily dosage for prescribed histamine2-receptor antagonists decreased (cimetidine from 694 to 454 mg, ranitidine from 280 to 183 mg) and the mean duration of therapy decreased from 14 to 10 months. The percentage of patients with potentially significant drug interactions decreased from 14.2 to 6.5 percent. The mean number of antiulcer agents dosage units dispensed per month decreased by 24,461 units, resulting in a projected annual savings of $327,273. There were no identifiable clinically important changes in the use of antacid products or prescribing of upper gastrointestinal studies.\n A cost-savings program sponsored by the pharmacy and therapeutics committee decreased costs, corrected prescribing to more closely meet preset criteria, and produced no discernable unfavorable effect on patient care.", "To evaluate the effectiveness of an automated prior authorization (PA) system (SmartPA) in reducing use of and expenditures for cyclooxygenase-2 (COX-2) inhibitors.\n Before and after with control group.\n After implementation of SmartPA in Missouri, changes in use of and expenditures for COX-2 inhibitors, COX-2 substitutes (traditional nonsteroidal anti-inflammatory drugs [NSAIDs] and other products for pain), and gastrointestinal (GI) protective agents were compared between the Medicaid program of Missouri and that of a state with no PA program for COX-2 inhibitors. Subjects were continuously enrolled for the 24-month study period and had a claim for a COX-2 inhibitor in the 12-month baseline period. Analyses included comparison of means and linear regression. Regressions controlled for age, sex, risk for GI complications, severity of illness, and the interaction between state and risk.\n Changes in expenditures for COX-2 inhibitors, NSAIDs, other pain drugs, and GI-protective drugs were $256 higher, $56 lower, $21 higher, and $198 higher, respectively, in the control state among low-risk patients. Changes in expenditures were $102 higher, $12 lower, $21 lower, and $185 higher, respectively, in the control state among high-risk patients. Results were similar for drug utilization.\n Implementation of SmartPA resulted in reduced use of and expenditures for COX-2 inhibitors and reduced net expenditures for all pain and GI-protective medications. These effects were greatest for patients at low risk for GI complications.", "State Medicaid programs introduce many types of prescribing restrictions to manage pharmaceutical use and expenditure. Little is known about the differential effect of implementing prior authorization (PA) policies at market entry versus waiting until several years later when prescribing behavior may already be established.\n We sought to examine the impact on overall use of Cox II inhibitors of PA policies implemented at market entry versus at least 2 years after market entry.\n We quantified Cox II inhibitor and nonselective nonsteroidal anti-inflammatory drug (NSAID) utilization for state Medicaid programs from January 1996 to September 2003. We used generalized estimating equations, Tukey's studentized range test and segmented linear regression on state Medicaid programs to determine the significance of changes in medication use.\n The primary end point was the number of defined daily doses (DDD) per 1000 population per day.\n Six states implementing prescribing restrictions for Cox II inhibitors at market entry had the lowest rates of uptake, averaging 10.9 DDD/1000/d. Twelve states adopting restrictions more than 2 years after market entry experienced declines in use from 23.0 DDD/1000/d before to 13.9 DDD/1000/d after the restrictions (P < 0.01). The 17 states that had never restricted access had the highest utilization, averaging 29.0 DDD/1000/d.\n Implementing prescribing restrictions at market entry of Cox II inhibitors was effective in restricting uptake. Despite the difficulty in changing well-established prescribing patterns, utilization in states implementing policies 2 years after market entry approached that of the early adopting states within 1 year. Clinical outcomes of such policies remain unknown.", "More than one-third of Medicaid programs and Medicare Part D plans use prior authorization (PA) policies to control the use of atypical antipsychotics (AAs). We used Medicaid and Medicare claims data to investigate how Maine's PA policy affected AA use, treatment discontinuities, and spending among schizophrenia patients initiating AA therapy. Patients initiating AAs during Maine's policy experienced a 29 percent greater risk of treatment discontinuity than patients initiating AAs before the policy took effect; no change occurred in a comparison state. AA spending was slightly lower in both states. Observed increases in treatment discontinuities without cost savings suggest that AAs should be exempt from PA for patients with severe mental illnesses.", "To assess the changes in prescribing of statins in Norway after implementation of the new reimbursement regulations for statins in June 2005.\n Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were the proportion of atorvastatin users switching to simvastatin and changes in the proportion of new statin users receiving simvastatin. Based on retail costs for all statin prescriptions dispensed in Norway, expenditure was measured in Norwegian currency.\n One-year prevalences of statin use increased from 6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the year after the new statin regulations. Of atorvastatin users (N = 131,222), 39% switched to simvastatin during the 13-month period after the implementation. The proportion of switching was higher in women (41%) than in men (36%). In May 2005, 48% of the new statin users received simvastatin. The proportion of new users receiving simvastatin increased rapidly after implementation of the new regulations to 68% in June 2005 and reached 92% in June 2006. Expenditure was reduced from 120 million to 95 million Euro when comparing the year before with the year after the new statin regulations.\n The new reimbursement policy for statins has had a great impact on physicians' prescribing of statins in Norway. Physicians in Norway acknowledge the importance of contributing to cost containment.", "With the growing need to provide prescription drug benefits to older patients and to contain costs, it will be necessary to direct that coverage so as to make expenditures as efficient as possible. We evaluated the clinical and economic consequences of coverage restriction for 3 leading proton pump inhibitors (PPIs) in a large-scale natural experiment.\n The study design was a time-trend analysis in the setting of a provincial drug benefits program in British Columbia, Canada. We studied all British Columbia residents aged 66 or older (N = 501,104) using linked data on all prescription drug dispensings, physician services, and hospitalizations between January 2002 and June 2004. The new policy restricted coverage to rabeprazole and required treatment failure with a histamine H2 blocker. More widely used PPIs (omeprazole, pantoprazole, and lansoprazole) had to be paid for out of pocket, unless the physician requested an exemption. The main outcome measures were utilization of PPIs, drug discontinuation rates, gastrointestinal hemorrhage rates, and drug expenditures.\n Utilization of the restricted PPIs declined sharply after the policy change (-14,850 daily doses per month per 10,000 residents, P < .0001), whereas use of the covered PPI increased sharply (+19,300, P < .0001), with 45% of all PPI users switching to the covered agent within 6 months. We found no increased use of H2 blockers or stopping of gastroprotective drugs. There was no increase in the monthly rate of hospitalization for gastrointestinal hemorrhage after the PPI restriction (P = .35) even though the study had the power to detect increases of 24 events per 10,000 residents with 95% confidence. There was a slight increase in physician visits 3 months after the policy change (P = .01) for a 2-month period when 9% of new rabeprazole users were switched back to a restricted PPI. In the first 6 months of the policy change, the provincial health plan saved at least 2.9 million Canadian dollars as a result of the policy change.\n Coverage restriction of 3 leading PPIs led to substantial utilization changes and savings, without increased noncompliance or clinical complication.", "Since its introduction in 1996, controlled-release (CR) oxycodone use has increased steadily despite its high cost. To control use and expenditures, many Medicaid programs have implemented CR oxycodone prior authorization (PA) policies. Few studies evaluate Medicaid policies or compare lenient and strict policies in multiple states.\n To estimate the impact of PA on CR oxycodone use by Medicaid beneficiaries.\n Secondary data analysis of 50 states' aggregate Medicaid prescription dispensing records,1996-2005. PA details were systematically collected. Regression and random effects meta-analyses estimated impact of strict and lenient PA policies on CR oxycodone use and expenditures.\n Change in rate of CR oxycodone use, proportion of long-acting opiates accounted for by CR oxycodone and average long-acting opiate dose expenditure.\n In 2004, CR oxycodone accounted for 12.4% of all opiates and 32.2% of long-acting opiates dispensed to Medicaid beneficiaries. Over the study period its use increased, on average, 109% annually, and 21 states implemented PA. PA was associated with state-specific use changes ranging from -76% to 9%. In aggregate, PA was associated with a nonsignificant decrease in CR oxycodone use, a significant 8% decrease in CR oxycodone as a proportion of long-acting opiate doses, and a small but significant change of -$0.31 in average cost per long-acting opiate dose. Strict policies were associated with greater changes.\n PA impact varied by state and was less dramatic than previously described Medicaid PA effects, suggesting CR oxycodone is relatively refractory to PA. A refined measure of such policies is needed to identify effective prescription management strategies.", "Medicaid expenditures for antipsychotic medications have risen rapidly, from under $1.0 billion in 1995 to over $5.5 billion in 2005. In response, at least ten states have implemented prior-authorization programs that restrict access to particular second-generation antipsychotic agents (aripiprazole and olanzapine). Twenty-two states restrict particular dosing forms (injections). This study examined the impact of such restrictions.\n The authors used interrupted time-series analysis of quarterly state-level drug utilization data to examine the impact of prior authorization for particular agents in West Virginia and Texas. Changes in market share of nonpreferred medications and total pharmacy costs were compared with changes in states without similar prior-authorization requirements.\n The West Virginia policy led to an immediate 3.5% reduction in market share level (p<.01) and a 1.3% decrease in trend per quarter in market share (p<.001) for nonpreferred antipsychotics, leading to a 13.9% reduction after two years. In Texas, prior authorization reduced the market share level of nonpreferred agents by 2.6% (p=.055). However, prior authorization did not lead to a significant decrease in pharmacy reimbursements in either state.\n Current prior-authorization policies for second-generation antipsychotics do not appear to reduce pharmacy reimbursement, probably because alternative medications are costly. These findings suggest that any cost savings from prior-authorization policies would accrue largely through supplemental rebate agreements with manufacturers, which are likely reduced by the transfer of dually eligible Medicaid enrollees to Medicare Part D plans. Further evaluation of the clinical consequences resulting from such policies is urgently needed to determine whether the minimal cost savings outweigh the potential clinical risks." ]

[ "9288368", "2675496", "8935744", "8623866", "2349410" ]

[ "Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea--a double-blind study.", "[Magnesium--a new therapeutic alternative in primary dysmenorrhea].", "Curative treatment of primary (spasmodic) dysmenorrhoea.", "Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents.", "[Therapeutic effects of magnesium in dysmenorrhea]." ]

[ "We evaluated the analgesic effect of Toki-shakuyaku-san (TSS) in women who had a combination of \"deficiency,\" of \"Yin,\" \"cold,\" and \"stagnated blood\" syndromes, and were suffering from dysmenorrhea. A diagnostic scoring system was used for determination of these conditions. We treated patients with either TSS or placebo during 2 menstrual cycles with a double-blind technique, and we followed them for 2 additional cycles. A significant alleviation of dysmenorrhea was observed in patients treated with TSS as compared to those treated with placebo. Our results suggest that TSS is effective for treatment of dysmenorrhea in patients with the above-mentioned conditions.", "50 patients suffering from primary dysmenorrhoea were treated with Magnesium (Mg 5-longoral, Artesan GmbH) in a double-blind study. After a six-month period 21 out of 25 women showed a decline of symptoms, only 4 ones reported no therapeutical effect. For monitoring treatment results prostaglandin F2 alpha (PGF2 alpha) was measured every second month. On Mg-therapy conditions we achieved a reduction of PGF2 alpha in menstrual blood to 45% of value before treatment started. As against that 90% of basic concentration were estimated from women who received a placebo. Probably, the specific therapeutical effect of Mg based on inhibition of biosynthesis of PGF2 alpha but also on its direct muscle relaxant and vasodilatory effect. Beside the PG-synthesis and ovulation inhibitors the use of Magnesium is a potential, natural opportunity to treat primary dysmenorrhoea, which is widely free of side effects.", "To prove the efficacy of oral vitamin B1 administration for the treatment of primary dysmenorrhoea, a randomised, double-blind, placebo-controlled study was carried out on 556 girls aged 12-21 yr, having moderate to very severe spasmodic dysmenorrhoea. Thiamine hydrochloride (vitamin B1) was given in a dose of 100 mg orally, daily for 90 days. The combined final results of both the 'active treatment first' group and the 'placebo first' group, after 90 days of vitamin B1 administration, were 87 per cent completely cured, 8 per cent relieved (pain almost nil to reduced) and 5 per cent showed no effect whatsoever. The results remained the same two months later as well when no drug was administered. Unlike all the current treatments which are suppression-oriented, this curative treatment directly treats the cause, is free from side effects, is inexpensive and easy to administer.", "The purpose of the study was to examine whether dietary supplementation with omega-3 fatty acids can relieve symptoms of dysmenorrhea in adolescents.\n Forty-two adolescents with dysmenorrhea were randomly allocated to two groups. In the first group 21 girls received fish oil (1080 mg icosapentaenoic acid, 720 mg docosahexaenoic acid, and 1.5 mg vitamin E) daily for 2 months followed by a placebo for an additional 2 months. In the second group 21 girls received placebo for the first 2 months, followed by fish oil for 2 more months. The Cox Menstrual Symptom Scale was used to assess response to treatment.\n There were no significant differences in the Cox Menstrual Symptom Scale between the two groups at baseline after 2 months of placebo administration. After 2 months of treatment with fish oil there was a marked reduction in the Cox Menstrual Symptom Scale from a baseline mean value of 69.9 to 44.0 (p < 0.0004).\n This study suggests that dietary supplementation with omega-3 fatty acids has a beneficial effect on symptoms of dysmenorrhea in adolescents.", "Primary dysmenorrhea is a common gynaecological symptom complex characterized by a painful syndrome occurring predominantly on the first and the second day of the cycle and associated with concomitant autonomic phenomena. In a randomized double-blind study, the therapeutic effect of magnesium has been investigated in 32 women (16 to 42 years old) who have been treated in the gynaecological outpatient-department at our clinic because of primary dysmenorrhea. The dosage of Magnesiocard comprised 3 X 5 mmol granulate orally on the day preceding menstruation and on the first and the second day of the cycle. At the end of the study, which covered six cycles, we were able to analyze the results in 21 patients, 11 having been treated with magnesium and 10 with placebo. While in the magnesium group only a slight effect was noted on the first day of the cycle under therapy when compared to both the placebo group and the dysmenorrhea disturbances persisting before therapy was started, magnesium had a therapeutic effect on both back pain and lower abdominal pain on the second and the third day of the cycle. Parallel to this therapeutic influence on the symptomatology of dysmenorrhea, a marked reduction in absences from work due to the dysmenorrhea was also noted. The possibilities of magnesium therapy in dysmenorrhea should be investigated further in multicentre studies." ]

[ "1549149", "10943876" ]

[ "Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group.", "Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis." ]

[ "The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials.\n Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed.\n The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity.\n Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.", "Juvenile idiopathic arthritis (JIA) can persist through adolescence and adulthood, resulting in significant disability. The use of low-dose oral methotrexate (MTX) for persistent polyarthritis has been shown to be effective by the USA/USSR collaborative study group. However, 2 of the most disabling subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in that study. The present study was therefore conducted to investigate the efficacy of MTX in these 2 subgroups.\n Patients under the age of 16 years who fulfilled the International League of Associations for Rheumatology criteria for systemic or extended oligoarticular arthritis were eligible for this multicenter, double-blind, placebo-controlled crossover trial. Forty-five patients with systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2 months. Core outcome variables were considered as primary measures, giving a final score of \"improved\" or \"not improved.\" Secondary measures included scores of systemic features and biochemical laboratory measures. Assessment of function was not included since there were no validated functional measures at the start of this trial in 1991.\n In the extended oligoarticular arthritis group, MTX treatment produced significant improvement in 3 of 5 core variables (erythrocyte sedimentation rate, physician's global assessment of disease activity, and parent's global assessment of disease activity). By the primary improvement criteria, there was significant overall improvement during MTX treatment. In the systemic arthritis group, only 2 of 5 core variables were significantly improved (physician's and parent's global assessment of disease activity). Systemic features were not part of the core variables, but the systemic feature score was not significantly different between MTX and placebo treatment. There was no significant overall improvement in this group during MTX treatment. However, no significant interaction between disease subgroup and treatment effect was demonstrated. When the data from both disease subgroups were combined, there was significant clinical improvement during MTX treatment (P = 0.006).\n MTX 15-20 mg/m2 given orally once a week was found to be an effective treatment for both extended oligoarticular and systemic JIA in this shortterm trial. Long-term efficacy needs to be addressed in future studies." ]

[ "17028377" ]

[ "Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women." ]

[ "Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc might play an important role in appetite regulation and its administration stimulates leptin production. However, there are few reports in the literature on its role on leptin levels in the obese population. The present work assesses the effect of zinc supplementation on serum leptin levels in insulin resistance (IR). A prospective double-blind, randomized, clinical, placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were similar for age, BMI, caloric intake, insulin concentration, insulin resistance, and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and 24- h urine were performed by using atomic absorption spectrophotometry. After 4 wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did not change in either group, although zinc concentration in the urine increased from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc supplementation (p < 0.05). Insulin did not change in the placebo group, whereas there was a significant decrease of this hormone in the supplemented group. HOMA also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc-supplemented group but did not change in the placebo group. Leptin did not change in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and did not change. More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation (with higher doses or longer intervals) or different measures." ]

[ "8116741", "3631181", "1497518", "8238220", "9052620", "11124286", "8008342" ]

[ "5-Fluorouracil after primary combined filtration surgery.", "A randomized study of 5-fluorouracil and filtration surgery.", "A randomized study of trabeculectomy and subconjunctival administration of fluorouracil in primary glaucomas.", "Trabeculectomy, phacoemulsification, and posterior chamber lens implantation with and without 5-fluorouracil.", "5-fluorouracil in combined trabeculectomy and clear-cornea phacoemulsification with posterior chamber intraocular lens implantation. A one-year randomized, controlled clinical trial.", "Randomized, controlled study of low-dose 5-fluorouracil in primary trabeculectomy.", "5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter study." ]

[ "We examined the safety and efficacy of 5-fluorouracil in eyes with open-angle glaucoma undergoing combined cataract removal and filtration surgery. We randomly assigned one eye each of 24 patients to receive 5-fluorouracil (five injections of 5 mg during two weeks after surgery) and one eye each of 20 patients to comprise the control group. Preoperatively, the two groups had similar mean intraocular pressure (P = .8) and number of medications (P = .2). The mean intraocular pressure of the 5-fluorouracil group was 18.6 +/- 1.1 mm Hg, with 2.5 +/- 0.3 medications; that of the control group was 18.2 +/- 1.2 mm Hg, with 2.2 +/- 0.2 medications. One year postoperatively, intraocular pressure and the number of medications were significantly reduced by a similar amount in both groups of patients (5-fluorouracil, 14.2 +/- 0.7 mm Hg, 0.8 +/- 0.2 medications; controls, 14.3 +/- 0.6 mm Hg, 1.0 +/- 0.2 medications). Transient superficial punctate keratopathy occurred more frequently (P = .04) in the 5-fluorouracil group (16 of 24 eyes, 67%) than in the control group (seven of 20 eyes, 35%). In our randomized and prospective study, the adjunctive use of 5-fluorouracil did not result in improved control of intraocular pressure one year after combined surgery in eyes with open-angle glaucoma.", "We conducted a randomized study of 26 patients with a poor prognosis undergoing filtration surgery with and without a low dose of 5-fluorouracil. Mean preoperative intraocular pressure (+/- S.E.M.) in the 5-fluorouracil group (n = 14) was 38.4 +/- 3.08 mm Hg; in the control group (n = 12) it was 41.2 +/- 5.0 mm Hg. Mean postoperative intraocular pressure (+/- S.E.M.) at six to 18 months was 14.4 +/- 1.4 mm Hg in the 5-fluorouracil group and 30.7 +/- 3.9 mm Hg in the control group (P less than .01). Of 14 patients in the 5-fluorouracil group, 12 had a successful outcome at 12 months. Of 12 patients in the control group, three had a successful outcome during this same interval.", "Forty-one adult patients with primary open angle glaucoma and nine adult patients with chronic angle closure glaucoma underwent trabeculectomy in one eye each. Twenty-one eyes with primary open angle glaucoma and four with chronic angle closure glaucoma were randomly assigned to receive four to six subconjunctival injections of fluorouracil for 10 days after surgery. Twenty-five control eyes did not receive fluorouracil. Intraocular pressure was 20 mm Hg or lower in 24 eyes (96%) in the treatment group after mean follow-up of 17.8 months and in 19 control eyes (76%) after mean follow-up of 17.5 months (P less than .05). Encapsulated bleb developed in three (12%) of the fluorouracil-treated eyes vs two (8%) of the control eyes. A few injections of fluorouracil adequately inhibited scarring. This might be explained by its toxic effect on existing fibroblasts. Overall, trabeculectomy with injection of fluorouracil was found to be efficacious and relatively safe. Further studies regarding late complications are required.", "Subconjunctival 5-fluorouracil has been an effective adjunct in glaucoma filtering surgery. We investigated the effectiveness of 5-fluorouracil in primary trabeculectomy combined with phacoemulsification and posterior chamber intraocular lens implantation (glaucoma triple procedure). Seventy-four patients were enrolled and randomly assigned into two groups to receive either no 5-fluorouracil (control patients) or low-dose 5-fluorouracil (mean total dose, 24.8 mg; mean number of injections, 5.0 +/- 1.3). The mean preoperative intraocular pressure was 20.1 +/- 5.4 mm Hg for the 5-fluorouracil group and 21.0 +/- 5.2 mm Hg for the control group (P = .48, Student's unpaired t-test). The mean number of medications was 2.2 +/- 1.0 and 2.0 +/- 1.0 (P = .49, Mann Whitney U test), respectively. At all postoperative visits, there were no statistically significant differences in mean intraocular pressures between the two groups. Mean follow-up was 13.2 months for 5-fluorouracil-treated patients and 15.0 months for control patients. At the last postoperative visit, mean intraocular pressures were 15.4 +/- 3.7 mm Hg and 15.0 +/- 5.0 mm Hg, respectively (P = .45, Student's unpaired t-test). Both groups showed comparable visual outcome (20/40 or better in 31 of 38 5-fluorouracil-treated patients [82%] vs 32 of 36 control patients [89%]) and a decrease in number of medications needed, 0.7 +/- 1.0 and 0.7 +/- 0.9, respectively (P = .96, Mann Whitney U test). Thus, 5-fluorouracil administered as in our study did not seem to have any effect in primary trabeculectomy combined with phacoemulsification and posterior chamber intraocular lens implantation.", "To test the effect of postoperative subconjunctival 5-fluorouracil (5-FU) on the pressure outcome in combined procedure (limbus-based trabeculectomy + clear-cornea phacoemulsification).\n Prospective randomized, controlled clinical trial; n = 24 eyes (24 patients) with concurrent open-angle glaucoma and cataract; 12 eyes per treatment group; sample size adjusted for a minimal expected difference in the event rate between the 2 treatment groups = 50%, control rate = 20%; type I error = 0.05; power = 95%. Uncomplicated limbus-based trabeculectomy + uncomplicated clear-cornea phacoemulsification + posterior chamber intraocular lens. The 5-FU group = five subconjunctival injections of 5 mg 5-FU, starting from day 8 after surgery, one injection per week. Control group = no injections. The groups were matched for age, preoperative intraocular pressure (IOP), duration of preoperative antiglaucoma treatment, preoperative pilocarpine and adrenergics, preoperative laser trabeculoplasty, and beta-blockers in the fellow eye. The IOP less than or equal to 15 mmHg without treatment 1 year after surgery (IOP = average of the two highest values measured in the diurnal curve, 8 AM to 6 PM, one reading every 2 hours).\n Each patient completed a 1-year follow-up. Ten of 12 eyes of the 5-FU group showed an IOP less than or equal to 15 mmHg at the end of follow-up versus 1 of 12 eyes in the control group (Fisher's exact test, P = 0.00064). The IOP range was 10 to 17 mmHg in the 5-FU group and 14 to 22 mmHg in the control group.\n Postoperative 5-FU may improve the 1-year success rate of trabeculectomy combined with clear-cornea phacoemulsification.", "To report a randomized clinical trial of postoperative subconjunctival injections of low-dose 5-fluorouracil in patients undergoing primary trabeculectomy.\n In a prospective, randomized clinical trial, 40 eyes of 40 patients were randomized to the low-dose 5-fluorouracil group and received three subconjunctival injections of 5 mg each over 11 postoperative days, and 40 eyes of 40 patients were randomized to trabeculectomy without 5-fluorouracil.\n Mean (+/-SD) preoperative and 1-year postoperative intraocular pressures in the 5-fluorouracil group were 26.9 (+/-9.5) and 15.3 (+/-5.8) mm Hg, respectively. In the control group these were 25.9 (+/-8.1) mm Hg, and 15.8 (+/-5.1) mm Hg, respectively. The patients who received 5-fluorouracil had a mean reduction in intraocular pressure of 11.5 (+/-9.1) mm Hg at a median follow-up of 52.3 weeks. The control group had a mean reduction in intraocular pressure of 10.2 (+/-8.7) mm Hg at a median follow-up of 52.6 weeks. These differences were not statistically significant.\n Three postoperative subconjunctival 5-fluorouracil injections of 5 mg each after trabeculectomy in eyes at low risk for failure had no statistically or clinically significant effect on reduction of intraocular pressure with 1-year follow-up. Enhancement of success in this group of patients may require a larger total dose of 5-fluorouracil.", "Postoperative subconjunctival 5-fluorouracil (5-FU) injections increase the success of filtration surgery in eyes with prior filtration failure or cataract removal and in eyes with secondary glaucoma. The authors evaluate the safety and benefit of adjunctive 5-FU in eyes undergoing initial trabeculectomy.\n Patients with phakic, uncontrolled, open-angle glaucoma who were undergoing initial trabeculectomy were prospectively assigned to the 5-FU group on the first postoperative day. Patients in this group received five 5-mg injections during 2 weeks after surgery. Patients in the control group received no injections.\n Preoperative intraocular pressure (IOP) and number of antiglaucoma medications were similar in the 5-FU (n = 32) and control (n = 30) groups. Transient superficial punctate keratopathy was the only postoperative complication that occurred more frequently (P < 0.05) in the 5-FU (14 eyes) than in the control eyes (3 eyes). Patients were followed for a minimum of 1 year or until a study endpoint was reached: IOP of 21 mmHg or greater with maximum medical therapy (2 5-FU eyes and 8 control eyes; P < 0.03) or cataract removal after filtration (5 treated and 3 control eyes). At last follow-up (mean, > 20 months), IOP and the number of antiglaucoma medications were significantly lower (P < 0.02) in the 5-FU eyes (IOP, 12.0 +/- 1.3 mmHg; medications, 0.2 +/- 0.1) than in the control eyes (IOP, 16.8 +/- 1.3 mmHg; medications, 0.8 +/- 0.2). Intraocular pressure was 20 mmHg or lower in 94% of 5-FU eyes and in 73% of control eyes (P < 0.03) and 16 mmHg or lower in 84% of 5-FU eyes and in 57% of control eyes (P < 0.02).\n Adjunctive 5-fluorouracil increases the rate of success, decreases the level of postoperative IOP, and reduces the need for postoperative antiglaucoma medication in eyes with open-angle glaucoma undergoing initial trabeculectomy." ]

[ "12555294", "8675164", "9409569", "15194628", "16703653" ]

[ "Effects of the intermittent Pringle manoeuvre on hepatic gene expression and ultrastructure in a randomized clinical study.", "Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers.", "Prospective evaluation of Pringle maneuver in hepatectomy for liver tumors by a randomized study.", "Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial.", "Randomized clinical trial of liver resection with and without hepatic pedicle clamping." ]

[ "The intermittent Pringle manoeuvre during hepatectomy results in a better clinical outcome when the accumulated ischaemia time is less than 120 min. The aim of this study was to investigate hepatic gene expression related to microcirculatory modulation and ultrastructural changes in patients having the intermittent Pringle manoeuvre.\n Forty patients who underwent hepatectomy for liver tumours were randomly assigned to liver transection with intermittent Pringle manoeuvre (Pringle group, n = 20) or without the manoeuvre (control group, n = 20). The clinical data and hepatic expression of endothelin (ET) 1 and endothelial nitric oxide synthase (eNOS) combined with liver ultrastructure were compared.\n The Pringle manoeuvre resulted in less blood loss (8.9 versus 12.4 ml/cm(2); P = 0.034), a shorter transection time (2.7 versus 4.1 min/cm(2); P = 0.015) and a lower serum bilirubin level on postoperative day 2 (26 versus 35 microm/l; P = 0.04). The hepatic messenger RNA content of ET-1 decreased by 38 per cent of the basal level in the Pringle group, whereas it increased by 28 per cent in the control group (P = 0.026). More patients in the control group showed swelling of mitochondria in hepatocytes and disruption of sinusoidal lining cells (12 of 20 patients versus three of 20 in the Pringle group; P = 0.008).\n The intermittent Pringle manoeuvre results in less disturbance of the hepatic microcirculation and better preservation of liver sinusoids after hepatectomy.", "Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes (PMN) may play a critical role in ischemia-reperfusion injury. To evaluate whether similar mechanisms are operative in human liver, six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were randomized for utilization of hepatic vascular exclusion (HVE) as a model of ischemia-reperfusion injury. Portal and systemic levels of acute reactant cytokines (interleukin 6 [IL-6], interleukin 1 [IL-1], tumor necrosis factor alpha [TNF-alpha]) and neutrophil adhesion in serial liver biopsy specimens were studied. Correlations among mediators, leukocyte adhesion, and markers of liver injury were also evaluated. Hepatic vascular exclusion resulted in substantial and reproducible changes in portal and arterial IL-6 levels in both cirrhotic and noncirrhotic patients. Portal and systemic cytokine levels were comparable in most instances, whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients. Negative correlations were found between IL-6 levels at the time of reperfusion and later TNF-alpha levels. IL-6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications. Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients. In cirrhotic patients, the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury. This study in humans shows that acute reactant cytokines are released during liver ischemia and, interestingly, that IL-6 levels strongly correlate with clinical and laboratory measures of injury. Further studies to evaluate possible causal relationship with hepatic injury are warranted, with emphasis on the role of IL-6 and PMN adhesion.", "To evaluate whether vascular inflow occlusion by the Pringle maneuver during hepatectomy can be safe and effective in reducing blood loss.\n Hepatectomy can be performed with a low mortality rate, but massive hemorrhage during surgery remains a potentially lethal problem. The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss, but there is a potential harmful effect on the metabolic function of hepatocytes. There has been no prospective randomized study to determine whether the Pringle maneuver can decrease blood loss during hepatectomy, improve outcome, or affect the metabolism of hepatocytes.\n From July 1995 to February 1997, we studied 100 consecutive patients who underwent hepatectomy for liver tumors. The patients were randomly assigned to liver transection under intermittent Pringle maneuver of 20 minutes and a 5-minute clamp-free interval (n = 50), or liver transection without the Pringle maneuver (n = 50). The surface area of liver transection was measured and blood loss during transection per square centimeter of transection area was calculated. Routine liver biochemistry, arterial ketone body ratio (AKBR), and the indocyanine green (ICG) clearance test were done.\n The two groups were comparable in terms of preoperative liver function and in the proportion of patients having major hepatectomy. The Pringle maneuver resulted in less blood loss per square centimeter of transection area (12 mL/cm2 vs. 22 mL/cm2, p = 0.0001), a shorter transection time per square centimeter of transection area (2 min/cm2 vs. 2.8 min/cm2, p = 0.016), a significantly higher AKBR in the first 2 hours after hepatectomy, lower serum bilirubin levels in the early postoperative period, and, in cirrhotic patients, higher serum transferrin levels on postoperative days 1 and 8. The complication rate, the hospital mortality rate, and the ICG retention at 15 minutes on postoperative day 8 were equal for the two groups.\n Performing the Pringle maneuver during liver transection resulted in less blood loss and better preservation of liver function in the early postoperative period. This is probably because there was less hemodynamic disturbance induced by the bleeding.", "The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury, respectively, during liver surgery. In this prospective clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning.\n Patients (n=68) were assigned randomly to three groups: (i) resection with the Pringle manoeuvre; (ii) with ischaemic preconditioning before the Pringle manoeuvre for resection; (iii) without pedicle clamping.\n Following the Pringle manoeuvre the mean arterial pressure increased transiently, but significantly decreased after unclamping as a result of peripheral vasodilation. Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre. In addition, ischaemic preconditioning protected against reperfusion-induced tissue injury.\n Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre.", "The purpose of this study was to compare the perioperative outcome of liver resection with and without intermittent hepatic pedicle clamping.\n Between June 2002 and June 2004, 126 consecutive patients with resectable liver tumours were randomized to undergo resection with (63 patients) or without (63 patients) intermittent hepatic pedicle clamping.\n The transection time was significantly higher in the group without hepatic pedicle clamping. The blood loss per cm(2) was similar in the two groups: 2.7 ml/cm(2) in the group with versus 3.2 ml/cm(2) in group without hepatic pedicle clamping (P = 0.425). In the subset of patients with an abnormal liver, there were no differences in blood loss per transection surface: 3.1 ml/cm(2) in the group with versus 2.9 ml/cm(2) in the group without clamping (P = 0.829). The rate of blood transfusions was not higher in the non-clamping group. No differences were observed in the postoperative liver enzyme serum levels, the in-hospital mortality (one patient in each group) or the number of complications.\n This study showed clearly that liver resection without hepatic pedicle clamping is safe, even in patients with a diseased liver.\n Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd." ]

[ "3538590", "7287798", "9665535", "9282188", "12585582", "6391415", "2071201", "2929297", "2929298", "3300142", "9282183", "7809641", "8550163", "11697692", "9529179", "3316238", "3584203", "7143496", "8745803", "7768655", "6737334", "6389558", "7136568", "3334235", "7211311" ]

[ "[Bandaging of Colles' fracture with plaster of Paris. Low dorsal bracing versus high circular plaster of Paris].", "Colles' fracture. How should its displacement be measured and how should it be immobilized?", "A comparison of 3 and 5 weeks immobilization for older type 1 and 2 Colles' fractures.", "Distal radius fractures: a prospective randomized comparison of fibreglass tape with QuickCast.", "Aberdeen Colles' fracture brace as a treatment for Colles' fracture. A multicentre, prospective, randomised, controlled trial.", "Early results after Colles' fracture: functional bracing in supination vs dorsal plaster immobilization.", "On immediate functional bracing of Colles' fracture.", "Fixation not needed for undisplaced Colles' fracture.", "Brace treatment of Colles' fracture.", "Functional treatment of Colles fracture.", "Is manipulation of moderately displaced Colles' fracture worthwhile? A prospective randomized trial.", "[A comparison of 2 methods of plastic cast fixation in treatment of loco classico radius fracture. A prospective, randomized study].", "A new functional brace for the treatment of Colles' fractures.", "Focused rigidity casting: a prospective randomised study.", "Minimally displaced distal radius fractures: do they need plaster treatment?", "Early mobilisation of Colles' fractures. A prospective trial.", "The value of early mobilisation in the treatment of Colles' fractures.", "Colles' fractures treated by plaster and polyurethane braces: a controlled clinical study.", "Early mobilization in the treatment of Colles' fracture: a 3 year prospective study.", "Length of immobilisation after fractures of the distal radius.", "Colles' fracture. Immobilisation in pronation or supination?", "Functional cast-bracing for Colles' fractures. A comparison between cast-bracing and conventional plaster casts.", "Treatment of Colles' fracture. A prospective comparison of three different positions of immobilization.", "A controlled prospective study of early mobilization of minimally displaced fractures of the distal radial metaphysis.", "A new thermoplastic casting material. A comparison between plaster of Paris and Hexelite." ]

[ "nan", "In a study of 250 consecutive cases of Colles' fracture, analysis of various radiographic criteria for displacement showed that only the measurements for dorsal displacement and radial displacement were independent of each other. These measurements suffice for the comparison of series. The fractures randomly were divided into five equal groups, immobilized according to five different techniques. The technique of immobilization was found to be of subordinate importance for the final results, which are determined by the original displacement and the success of reduction.", "In a prospective study of Colles' fractures, 100 patients with Older type 1 and 2 fractures were randomized in two groups. One group was immobilized for 3 weeks and the other one for 5 weeks. Both groups were immobilized with a below-elbow plaster splint. At 1 year follow-up, there were 73 patients with 74 fractures. Dorsal angulation, radial length, wrist motion, grip strength and pain were measured. There was no significant difference in the measured parameters in the two groups. We found that 3 weeks of immobilization is a satisfactory treatment for Older type 1 and 2 Colles' fractures.", "Cast immobilization remains the most commonly employed method in the treatment of distal radius fractures. In an effort to test a new shrinkable polymer-coated casting material (QuickCast), a prospective randomized study was performed on 30 consecutive distal radius fractures. Fractures were divided into three groups based on the severity of fracture and treated with either a conventional short-arm fibreglass tape cast or a QuickCast. Results showed no significant differences in minor cast complications or maintenance of fracture reduction between conventional fibreglass tape and the QuickCast material. The shrinkable QuickCast, however, resulted in an average of one less cast change in all groups. This reduction in time and labour must be weighed against the slightly increased cost of the QuickCast immobilizer.", "We carried out a randomised, prospective, multicentre clinical trial of the treatment of Colles' fractures. A total of 339 patients was placed into two groups, those with minimally displaced fractures not requiring manipulation (151 patients) and those with displaced fractures which needed manipulation (188 patients). Treatment was by either a conventional Colles' plaster cast (a control group) or with a prefabricated functional brace (the Aberdeen Colles' fracture brace). Similar results were obtained in both groups with regard to the reduction and to pain scores but the brace provided better grip strength in the early stages of treatment. This was statistically significant after five weeks for both manipulated and non-manipulated fractures. At the tenth day the results were statistically significant only in manipulated fractures. There was no significant difference in the functional outcome between the two treatment groups. However, younger patients and those with less initial displacement had better functional results.", "A randomized clinical study of functional bracing in supination (FUSU) versus dorsal plaster immobilization (DPI) was conducted in 145 patients with Colles' fracture. A dynamic wrist unit was developed and used in 68 patients allocated for FUSU. The anatomical end result after FUSU was excellent or good in 80% of the patients versus 64% after DPI (P less than 0.05), in particular due to less dorsal angulation (P less than 0.001) and less radial shortening. The functional recovery was equal after 7 weeks and 3 months. At 6 months, 92% satisfactory results were achieved after FUSU versus 86% after DPI (P less than 0.05). Both anatomical and functional benefits were recorded in Frykman type V, VI, and VIII fractures and in the group of displaced intra-articular fractures. The functional benefit from FUSU is suggested primarily to be secondary to decreased fracture redislocation.", "A prospective randomized trial was carried out in 60 consecutive patients with Colles' fractures requiring manipulation. They were treated by either a standard Colles' plaster (control group) or in a functional plaster brace applied immediately after reduction of the fracture. The brace extended from the proximal radius and ulna to the level of the radial styloid and allowed a full range of movement at the radiocarpal joint. Both groups comprised 30 patients and were matched for age, sex and dominance of hand. There was no significant difference in initial severity of fracture or the quality of reduction. Radiological results on cast removal (35-42 days) were significantly better in the brace group compared with those treated with a below-elbow cast (P less than 0.05). Wrist function was also significantly better in the brace treated group at 12 weeks after fracture (P less than 0.05). This brace has a number of advantages over standard plaster treatment, but requires a degree of skill and experience in its application. A prefabricated brace has now been developed with a similar 'built in' three-point loading which will be easier for inexperienced staff to apply.", "A series of 68 undisplaced or minimally displaced Colles' fractures was randomized into two groups undergoing treatment with either a plaster cast or an elastic bandage. Pain, function, grip strength, and range of motion were evaluated 1 year later. There was a difference in the functional outcome in favor of the patients treated with an elastic bandage, who did not have more fracture redislocations than those treated with a plaster cast.", "Twenty patients with Colles' fractures were treated with a functional brace that allows wrist motion. The result was compared with a similar group of patients treated with a plaster cast. Dorsal displacement of the fracture was less and wrist function was better in the brace group. Swelling of the hand during the early stages was observed in the brace group; and because this may necessitate brace adjustment, increased medical supervision is necessary for this period.", "nan", "Thirty elderly patients with moderately displaced Colles' fractures were randomly assigned to manipulation under Bier's block or plaster immobilization alone. Moderately displaced was defined as 10 degrees to 30 degrees of dorsal angulation and less than 5 mm of radial shortening compared with the uninjured side. The groups were well matched for age, sex, fracture type and displacement; immobilization time and rehabilitation were standardized. The outcome measures were: radiological position at union, the functional score of Gartland and Werley, grip strength, cosmesis and algodystrophy assessment. There was no detectable difference between the groups in any of the outcome measures. Two-thirds of the correction of dorsal angulation achieved by manipulation was lost by 5 weeks. We conclude that up to 30 degrees of dorsal angulation and 5 mm of radial shortening may be accepted in selected elderly patients.", "The purpose of this study was to compare the functional and radiological result of two different positions of the wrist in a plaster cast following Colles' fracture. For this prospective study, each of 50 patients with type A 2.2, A 3.3, C 1.2 or C 2.2 (AO classification) fractures of the radius was randomly assigned to one of two groups. Both groups were treated in the same way as far as anaesthesia and reduction were concerned. The only difference in treatment lay in the position of fixation in plaster. In group 1 the wrist was immobilized in neutral flexion-extension. In group 2 the wrist was dorsiflexed 20 degrees, while the carpus was pushed in a volar direction by an impression in the plaster cast. At review 2-7 years after the accidents, the two groups were compared with reference to symptoms, range of motion at the wrist, power of first closure and radiographic appearance. In group 1 there were 5 patients with significant disability, compared with only 1 in group 2. A significant difference was found in the range of movement between the two groups for flexion and ulnar abduction (p < 0.01). The loss of power of first clenching (difference between injured and healthy hand) was 6.2 mmHg for group 1 and 3.8 mmHg for group 2 (not significant). The radiographic examination showed significant differences both in sagittal inclination (p < 0.001) and in radial shortening (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "A new prefabricated brace for the functional treatment of Colles' fractures has been developed. It is applied at fracture reduction and maintains fracture position by the application of three-point loading. In a prospective randomized clinical trial treating 85 displaced Colles' fractures, with blind independent follow-up, the brace gave better functional results than conventional plaster treatment. The improved function was apparent up to 6 months after injury. Finger function and pinch strength were also better in the brace-treated patients. Anatomical results were similar in the two groups.", "Focused rigidity casting was compared with standard casting in a randomised prospective study. Two hundred consecutive patients attending a fracture clinic were assigned to have either a standard cast consisting of synthetic or plaster of paris, or a focused rigidity cast of synthetic material. Patients were assessed using a specially developed scoring system termed the Bradford Plaster Index. In patients with fractures of the base of fifth metatarsal, focused rigidity casting proved superior to traditional techniques for ability score (p=0.0001), satisfaction score (p=0.0023), overall impairment of function (p=0.019), limitation of movement following cast removal (p=0.024) and in limitation of muscle strength following cast removal (p=0.001). In fractures of the distal radius, focused rigidity casting was superior for ability score (p=0.0002) and satisfaction score (p=0.00009). Patients with scaphoid fractures were better for satisfaction score (p=0.0483). Compared with the standard technique, focused rigidity casting has been shown to be superior to traditional methods with regard to satisfaction and functional scores without any detriment to clinical results.", "In a prospective, randomized trial, minimally displaced distal radius fractures were divided into two groups: those treated with plaster immobilization for 1 week compared with 3 weeks. Functional Cooney scores were determined at 6 weeks, 3 months, 6 months, and 1 year. No statistical differences could be found in functional outcome between the groups at any time during the evaluation. Although patients did not allow immediate functional treatment in the presence of a fracture, we could not find any differences between 1 week or 3 weeks of plaster treatment. No further dislocation occurred, and all patients experienced eventful healing with good and excellent results in 92% of the cases. We believe, therefore, that only minimal immobilization is required in these fractures and that they should be mobilized as soon as comfort allows.", "The results of a prospective controlled trial of early mobilisation of Colles' fractures in the elderly are presented. Early mobilisation produced less pain and a stronger grip. It did not lead to any greater loss of reduction of the fracture. However, there was no significant improvement in the final range of movement of the wrist. Immobilisation of the wrist for six weeks in plaster is extremely inconvenient for the elderly living alone and the patients greatly appreciated the reduction of this period of time to a minimum.", "Unilateral Colles' fractures in 187 patients over the age of 55 years were studied in a randomised prospective trial: 97 fractures were minimally displaced and were treated either conventionally or in a crêpe bandage; 90 displaced Colles' fractures were reduced and of these 47 were treated conventionally while 43 were encouraged to mobilise the wrist in a cast which restricted extension. Early wrist movement hastened functional recovery and led to earlier resolution of wrist swelling. Discomfort was no greater than in patients who were treated conventionally. The bony deformity, which recurred irrespective of the method of treatment, was not adversely affected by early mobilisation.", "In a prospective randomized controlled trial polyurethane casts and traditional plaster-of-Paris braces were compared in 46 cases of Colles' fractures of the forearm. Secondary fracture dislocation, subjective inconveniences, and the need for secondary adjustment of the cast were recorded. No significant difference was observed in the two groups. In comparison with plaster the synthetic bandage is lighter, water repellent, and hardens faster, and as far as circular bandages are concerned, they have zippers. It is concluded that polyurethane braces are a good supplement to plaster-of-Paris bandage in such fractures and recommended in selected cases.", "Ninety consecutive women with unilateral Colles' fractures were randomized into two different treatment groups. The control group was treated for 5 weeks in conventional short-arm, below the elbow plaster of Paris casts. The other group (N = 45) was treated similarly in plaster casts for 3 weeks and then had flexible casting applied for the remaining 2 weeks which allowed for early joint mobilization. Functional recovery was assessed by measuring grip strength and joint mobility at intervals over the 3 years. Radiographic and overall assessments were also made during 3 year course of study. Virtually all patients reported greater comfort after switching to the flexible casting. Mean grip scores and joint mobilities were higher at all time points with early mobilization, reaching levels of statistical significance at 6 months for grip score and at 3 months for joint mobility. By 3 years most differences between treatment groups had resolved. We found no evidence that early mobilization was detrimental to recovery. We conclude that early mobilization is a satisfactory treatment option for Colles' fracture, and may, in fact, hasten functional recovery.", "Thirty-three patients with undisplaced fractures of the distal radius were included in a clinical controlled trial with the purpose of evaluating whether it was safe to reduce the time of immobilisation in a plaster splint from 5 to 3 weeks. We did not find any difference in radiological healing at 3 months or in the functional scores after 3 and 9 months.", "nan", "The use of Orthoplast cast-bracing to allow early hand function in the treatment of displaced Colles' fractures was investigated in 243 patients. They were randomly allocated into three groups: in the first a conventional Colles' type plaster was used; in the second an above-elbow cast-brace with the forearm in supination; and in the third a below-elbow cast-brace. Radiographic measurements were made at each stage of treatment, and the final anatomical result was scored using Sarmiento's (1975) criteria. Function was assessed at three months and at six months. The anatomical result was not influenced by the method of immobilisation but was related to the efficacy of reduction. Loss of position in the braces was no greater than in plaster. The functional result at three months also was uninfluenced by the method of immobilisation; it was, however, related to the severity of the initial displacement, and (to a lesser degree) to the anatomical result, an effect which was lost at six months. Early hand function and the supinated position advocated by Sarmiento were found to confer no anatomical or functional advantage; we could see no reason to change from the use of conventional plaster casts in the treatment of uncomplicated Colles' fractures.", "The usual treatment of Colles' fracture, i.e. fracture of the distal radius with dorsal angulation of the distal fragment, is closed reduction and immobilization in a plaster cast. The position of the forearm in the cast varies, according to the reports of various authors. Forty-two extra-articular-fractures of the distal radius have been randomly divided into three groups. All were reduced, and the forearms were then immobilized in three different positions of rotation according to the grouping. The study indicates that the position of the forearm during immobilization is of importance as regards redislocation. After application of a plaster cast with the forearm in pronation there seems to be less likelihood of redislocation occurring than when the forearm is immobilized in supination (P less than 0.05).", "A controlled prospective trial of early exercise of slightly displaced fractures of the distal radial metaphysis has been performed. Twenty-eight fractures were enclosed in a tubigrip support 7-13 days after injury and 28 fractures were splinted in below-elbow plaster for 4 weeks. It was found that early movement of the wrist produced a superior functional result at 5 and 7 weeks (P less than 0.05) and allowed an earlier recovery of domestic skills (P less than 0.05). Early exercise did not improve recovery of strength of grip and did not produce a higher incidence of malunion. Patients treated in tubigrip experienced no more pain in weeks 4 and 6 and apart from one failure, no patient actively disliked this form of treatment and 22 were totally satisfied.", "Plaster of Paris and Hexelite, a new thermoplastic bandage, were compared in the treatment of 183 patients with malleolar fractures, Colles' fractures or distortions of the finger joints. There were no statistically significant differences between the two types of bandages taking into account the strength of the bandage, the amount of skin damage and the patient's opinion of the bandage. Hexelite is seven times more expensive than plaster of Paris, and, in addition, is more difficult to handle. Hence its use has been discontinued." ]

[ "9695300" ]

[ "Salbutamol or mist in acute bronchiolitis." ]

[ "The role of bronchodilators in the treatment of bronchiolitis remains controversial.\n A double-blind, placebo controlled trial was performed to evaluate the clinical response to nebulized salbutamol. One hundred and fifty-six infants aged between 7 weeks and 24 months who had had an episode of wheezing and other signs and symptoms of bronchiolitis were randomized to three groups as follows: (i) nebulized salbutamol was administered to 52 patients in group I at a dose of 0.15 mg/kg in 2 mL saline; (ii) saline was nebulized to 52 patients in group II and (iii) in group III 52 patients received mist in a tent. All three groups were administered oxygen during the procedures. Treatment was repeated with the same agent after 30 min if the respiratory score was 5 or more. Respiratory rate, heart rate, oxygen saturation and presence of cyanosis, wheezing, retractions were recorded before and after each treatment.\n The decrease in the respiratory score was 5.2 +/- 1.8, 0.82 +/- 2.4 and 1.7 +/- 1.3 in group I, II and III, respectively. The decrease in group I was significantly higher than in the other groups. Heart rate was similar between groups. Oxygen saturation decreased in group I without reaching statistical significance.\n Salbutamol was shown to be effective and safe in the treatment of acute bronchiolitis." ]

[ "12902914", "8078010", "9607475" ]

[ "Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter.", "A prospective randomized double-blind trial of bolus urokinase in the treatment of established Hickman catheter sepsis in children.", "A prospective randomized trial of urokinase as an adjuvant in the treatment of proven Hickman catheter sepsis." ]

[ "To assess the ethanol-lock technique as a means of treating central venous line infections. Bloodstream infections in patients with tunneled central venous catheters can lead to removal of the lines.\n Twenty-eight children and adolescents aged 2 to 18 years, with different types of cancer, had Broviac catheters and presented with positive blood culture and clinical signs of infection between January 2000 and December 2001. The ethanol-lock technique was performed 24 times in 18 patients in addition to empiric (initially) and specific (after antibiogram) intravenous antibiotic treatment. In another 15 cases, 13 children were treated with systemic antibiotics alone.\n Sixty-seven percent of the patients treated with ethanol locks had no infectious relapse of any kind within 4 weeks of treatment or during subsequent aplasia, compared with 47% treated with systemic antibiotics alone. In one boy the catheter infection could not be cleared with systemic antibiotics alone, but after one course of ethanol locks no more blood culture-positive infectious episodes were observed. No severe clinical side effects of ethanol flush were observed. Mild symptoms that occurred were tiredness, headaches, dizziness, nausea, and light-headedness.\n The ethanol-lock technique appears to be a safe, well tolerated, and effective way to treat central venous line infections, even in small children. A prospective randomized study should be designed to compare antibiotic-lock, ethanol-lock technique, and systemic antibiotics alone in the treatment of device-associated bloodstream infection.", "The incidence of Hickman catheter sepsis is 10% to 40%, with resultant catheter loss in one third of infections. Urokinase causes dissolution of colonized intracatheter fibrin thrombi and may improve salvage.\n To evaluate the efficacy of 12-hour-interval slow-push urokinase infusion in addition to standard antibiotic therapy in the treatment of catheter sepsis in a pediatric oncology population.\n A two-arm randomized double-blind trial was undertaken, with catheter salvage rate as the end point. Patients with Hickman catheter sepsis were randomized after culture data confirmed the diagnosis. The study drug was administered by a slow intravenous push and given at 12-hour intervals for a total of four doses. The catheters were aspirated after 1 hour.\n The trial was stopped after 41 patients were entered into the study; 18 patients received a placebo, and 23 received the urokinase. In the placebo group, six catheters were lost; in the urokinase group, eight were lost. The rate of bacterial clearance was equivalent for both. After administration of the study drug, each group had three episodes of fever and chills; two of these resulted in hypotension (one in each group). The authors conclude that slow-push urokinase infusion during established Hickman catheter sepsis does not result in improved catheter salvage or bacterial clearance. Slow intravenous push infusions in this setting may provoke hemodynamic instability even after initiation of antibiotics.", "Chronic vascular access catheters have become an important adjunct to the treatment of children with complex medical diseases, particularly malignancy. One of the major complications of chronic venous access devices is bacterial infection of the catheter site and bloodstream. Infusion of systemic antibiotics directly into the catheter has been the standard initial therapy with failure leading to catheter removal and replacement. It has been suggested by a number of investigators that the addition of urokinase as a thrombolytic agent to lyse any accumulated thrombus or fibrin would increase the successful catheter clearance by antibiotics. This study was designed as a prospective, randomized trial to compare treatment of children with positive catheter blood cultures with either antibiotics alone or in combination with urokinase 5,000 U boluses 12 and 24 hours after study entry.\n A total of 63 patients were entered in the study. Thirty-three received antibiotics and urokinase, and 30 received antibiotics alone.\n A total of 45 catheters (71%) were cleared of infection and salvaged. Treatment failures leading to catheter removal occurred in 9 of 33 in the experimental group and 9 of 30 in the control population (no significant difference).\n Urokinase could not be shown to act as an adjuvant in the clearance of infection from chronic central venous access catheters that had no evidence of clot or thrombus. This study required the performance of a dye study and excluded any patient with a known thrombus. This conclusion must therefore be limited to patients with no evidence of a clot or fibrin sheath." ]

[ "9430812", "17980550", "9973149", "18047869", "9820261", "17335465", "11014390", "3412591", "8912507", "11973011", "8129762", "7575714", "9781549", "1738571", "16275598", "10150323", "3535811", "2465530", "1560801", "3521612" ]

[ "A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics.", "Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms.", "A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder.", "Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury.", "Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS.", "Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy.", "Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.", "Amitriptyline, but not lorazepam, relieves postherpetic neuralgia.", "A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia.", "Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial.", "Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial.", "Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia.", "Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial.", "Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial.", "Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial.", "A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.", "A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia.", "Central post-stroke pain--a controlled trial of amitriptyline and carbamazepine.", "Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy.", "Evaluation of amitriptyline in primary fibrositis. A double-blind, placebo-controlled study." ]

[ "To compare amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics.\n A double-blind, crossover trial of treatment with amitriptyline, maprotiline, and placebo. Treatment was given in randomized order for periods of 4 weeks. Each period was separated by a 1-week washout. The final dose was 75 mg/day for both amitriptyline and maprotiline.\n Thirty-seven patients with diabetic and nondiabetic painful polyneuropathy.\n The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale (0 = no pain and 10 = worst thinkable pain) and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale (pain relief scale). For the assessment of depression, the Comprehensive Psychopathological Rating Scale (CPRS) was used.\n Using the global assessment of pain relief at the end of each treatment period, 22 of 33 patients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo treatment (p < .0001 and p < .05 for amitriptyline and maprotiline, respectively, against placebo). Amitriptyline was slightly better than maprotiline (p < .05) [tested by repeated measures analysis of variance (ANOVA)]. The order in which treatments occurred and the diagnosis of diabetes or nondiabetes did not have any significant effect on the global rating of pain relief. The mean values of the daily ratings of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetics at baseline. The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than placebo in relieving the pain (p < .0001 and p < .01, respectively, post hoc test according to Scheffé). However, there was no significant difference between the pain reduction of amitriptyline compared with maprotiline when assessing pain reduction with the 10-step verbal scale during the 4th treatment week. Nor was there a significant difference between diabetics and nondiabetics with regard to the effect of the drugs. The clinical effect was not significantly correlated to plasma concentration of either amitriptyline and its active metabolite nortriptyline or maprotiline in the global or daily assessments. The effect of treatment was not correlated to any particular pain quality nor to the intensity of pain. Depression was noted in three patients who completed the medication trial, but the effect of treatment of pain and depression did not clearly correlate. The adverse side effects of amitriptyline and maprotiline were common, and in 5 patients the medication had to be discontinued because of severe side effects.\n From the present results and the literature, it is concluded that tricyclic antidepressants with a pharmacologic profile similar to amitriptyline are the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients.", "Neuropathy is common in patients receiving vinca alkaloids, platinum derivatives, or taxanes. This double-blind, randomized, placebo-controlled study assessed the efficacy of low-dose amitriptyline to relieve chemotherapy-induced symptoms in 44 patients (age 20-65 years) who had neuropathic symptoms (numbness, tingling, pain) with a severity of > or =3/10. They were treated with amitriptyline for eight weeks (10mg/day to start, then dose elevation of 10mg/week up to 50mg/day if tolerated, followed by a stable dose > or =4 weeks). The patients completed a diary twice weekly, noting the intensity of pain, numbness and tingling, global improvement, and adverse effects. Neurological examination was performed at each visit (baseline, four, and eight weeks). The patients assessed both intensity and relief of pain, and overall discomfort. They also completed the Neuropathic Pain Scale and validated measures of anxiety and depression, and quality of life (QoL). The results demonstrated that amitriptyline did not improve sensory neuropathic symptoms, although there was a trend toward global improvement and improved QoL in favor of the amitriptyline group. No statistical significance was reached, probably due to the small number of patients and too low dose of amitriptyline. Amitriptyline was well tolerated.", "To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder.\n In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo.\n Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable.\n The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems.", "To test the hypotheses that both amitriptyline and gabapentin are more effective in relieving neuropathic pain than an active placebo, diphenhydramine.\n Randomized, controlled, double blind, triple crossover 8-week trial.\n Veterans Affairs medical center.\n Community dwelling adults with spinal cord injury (N=38) were recruited by telephone, letters, and flyers.\n Eight-week trial each of amitriptyline, gabapentin, and diphenhydramine.\n Pain intensity measured with a 10-cm visual analog scale (VAS) and an 11-point (0-10) numeric rating scale (NRS) and depressive symptomatology measured with the Center for Epidemiologic Studies Depression Scale-Short Form (CESD-SF).\n Baseline VAS scores for participants with low (< 10) CESD-SF scores was 4.61 and for those with high scores (> or = 10) it was 7.41. At week 8, in participants with high baseline CESD-SF scores, amitriptyline (mean, 4.21) was more effective than diphenhydramine (mean, 6.67; P=.035), and there was a nonsignificant trend suggesting that amitriptyline may be more effective than gabapentin (mean, 6.68; P=.061). Gabapentin was no more effective than diphenhydramine (P=.97). There was no significant difference among the medications for those with lower CESD-SF scores. Results could not be attributed to dropout rates, order or dose of medications, amount of medication taken for breakthrough pain, or side effects.\n Amitriptyline is more efficacious in relieving neuropathic pain than diphenhydramine at or below the level of spinal cord injury in people who have considerable depressive symptomatology.", "Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available.\n To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients.\n Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo.\n Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities.\n Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option).\n Standardized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks.\n Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily.\n Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the \"active\" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P=.88) and for patients in the amitriptyline group vs those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P=.99).\n In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.", "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.", "Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case.\n In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale.\n A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline.\n These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine.", "In a double-blind, randomized, crossover study, 58 patients with postherpetic neuralgia received 6-week courses of amitriptyline, 12.5 to 150 mg/d; lorazepam, 0.5 to 6 mg/d; or lactose placebo. Doses were titrated to the maximum level tolerated. Patients rated pain in a diary, using lists of verbal descriptors. Forty-seven percent of patients reported moderate or greater relief with amitriptyline, 16% with placebo, and 15% with lorazepam. Mean amitriptyline dose was 65 mg/d. Greater relief was associated with higher amitriptyline doses, up to the maximum dose of 150 mg/d, and with higher serum tricyclic levels. Lorazepam did not relieve pain and was associated with severe depressive reactions in four patients.", "To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM).\n Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales (VAS) for global well-being (1 completed by the physician and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening.\n Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS for pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score.\n Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone.", "Chronic pain in persons with spinal cord injury (SCI) is a difficult problem for which there is no simple method of treatment. Few randomized controlled trials of medications for pain in persons with SCI have been conducted. This study was designed to determine whether amitriptyline, a tricyclic antidepressant, is efficacious in relieving chronic pain and improving pain-related physical and psychosocial dysfunction in persons with SCI. Eighty-four participants with SCI and chronic pain were randomized to a 6-week trial of amitriptyline or an active placebo, benztropine mesylate. All pre- and post-treatment assessments were conducted by evaluators blind to the allocation. Regression analyses were conducted to examine whether there was a medication group effect on the primary (average pain intensity) and secondary outcome measures. No significant differences were found between the groups in pain intensity or pain-related disability post-treatment, in either intent-to-treat analyses or analyses of study completers. These findings do not support the use of amitriptyline in the treatment of chronic pain in this population, but we cannot rule out the possibility that certain subgroups may benefit.", "To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine.\n Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo.\n After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response.\n Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.", "To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non-rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline.\n Twenty-two patients with fibromyalgia were studied in a 2-month, double-blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2-month treatment period.\n Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance.\n The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.", "OBJECTIVE (BACKGROUND): Amitriptyline (AT) is a standard therapy for postherpetic neuralgia (PHN). Our hypothesis was that nortriptyline (NT), a noradrenergic metabolite of AT, may be more effective.\n A randomized, double-blind, crossover trial of AT versus NT was conducted in 33 patients.\n Thirty-one patients completed the trial. Twenty-one of 31 (67.7%) had at least a good response to AT or NT, or both. We found no difference with regard to relief of steady, brief, or skin pain by visual analog scales for pain and pain relief; mood; disability; satisfaction; or preference between the two drugs. Intolerable side effects were more common with AT. Most patients (26/33) were not depressed, and most responding showed no change in rating scales for depression despite the occurrence of pain relief.\n We concluded that this study provides a scientific basis for an analgesic action of NT in PHN because pain relief occurred without an antidepressant effect, and that although there were fewer side effects with NT, AT and NT appear to have a similar analgesic action for most individuals.", "Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails.", "In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate trial of any antidepressant, we performed a randomized, double-blind, parallel design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60 mg/day for fluoxetine over a 3-week period and then treated for an additional 3 weeks before tapering off study medication. A total of 38 subjects (81%) completed the entire trial. The modified intent-to-treat analysis of percent change in daily diary pain intensity scores showed no significant differences among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%). Clinically meaningful pain relief (moderate or better) was significantly more likely with desipramine (12/15 patients) than with amitriptyline (9/17) or fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry had smaller reductions in pain than those not using concomitant opioids. The fluoxetine group had the highest noncompletion rate (33%), with 1 subject hospitalized for hyponatremia. Although the magnitude of pain reduction and the category pain relief rating was not significantly different among the 3 drugs, the tricyclics desipramine and amitriptyline were well tolerated and provided clinically meaningful pain relief in 53% to 80% of subjects.\n Few clinical trials focus on patients who are naïve to an entire class of medication. In this randomized blinded trial, the tricyclic antidepressants desipramine and amitriptyline were compared to the serotonin-selective antidepressant fluoxetine. All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in 80% of those treated.", "An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.", "Sixty-two patients with fibromyalgia were randomly assigned to receive 25 mg of amitriptyline at night, 500 mg of naproxen twice daily, both amitriptyline and naproxen, or placebo in a 6-week, double-blind trial. Amitriptyline was associated with significant improvement in all outcome parameters, including patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score. Patients taking the combined naproxen-amitriptyline regimen experienced minor, but not significant, improvement in pain when compared with patients who took amitriptyline alone. Amitriptyline, or amitriptyline and naproxen, is an effective therapeutic regimen for patients with fibromyalgia.", "A double-blind, 3-phase, cross-over, placebo-controlled trial of the pain-relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post-stroke pain (CPSP) but without signs of depression. Treatment was given, in randomized order, for periods of 4 weeks, separated by 1 week wash-out. The final doses were 75 and 800 mg/day, respectively, for amitriptyline and carbamazepine. The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale. For the assessment of depression the Comprehensive Psychopathological Rating Scale (CPRS) was used. Amitriptyline produced a statistically significant reduction of pain when compared to placebo. According to the global rating, 10 of the 15 patients were responders to this drug. The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration, since the median total ami- and nortriptyline concentrations were 497 and 247 nmol/l, respectively, for responders and non-responders. The early onset, together with the fact that the patients were not depressed, nor did they obtain reduced scores on ratings of depressive symptoms and signs, provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect. Five of the 14 patients treated with carbamazepine reported some pain relief, but the effect did not reach statistical significance when compared to placebo. No correlation was found between effect and plasma concentration. In general, the patients tolerated the planned final dose of amitriptyline well. No final dose reduction was necessary. Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients. However, only 1 patient had to be taken off medication, on day 25, due to drug interaction.", "Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions. Selective agents might be safer and more effective.\n We carried out two randomized, double-blind, crossover studies in patients with painful diabetic neuropathy, comparing amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients, and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients. Fifty-seven patients were randomly assigned to a study as well as to the order of treatment, permitting comparison among all three drugs and placebo as the first treatment. The patients rated the degree of pain present each day using verbal descriptors, and they also assessed the extent of pain relief globally at the end of each treatment period.\n After individual dose titration, the mean daily doses of the drugs were as follows: amitriptyline, 105 mg; desipramine, 111 mg; and fluoxetine, 40 mg. There was moderate or greater relief of pain in 28 of the 38 patients (74 percent) who received amitriptyline, 23 of the 38 patients (61 percent) who received desipramine, 22 of the 46 patients (48 percent) who received fluoxetine, and 19 of the 46 patients (41 percent) who received placebo. The differences in responses between amitriptyline and desipramine and between fluoxetine and placebo were not statistically significant, but both amitriptyline and desipramine were superior to placebo. Amitriptyline and desipramine were as effective in patients who were not depressed as in depressed patients, but fluoxetine was effective only in depressed patients.\n Desipramine relieves pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the latter. Blockade of norepinephrine reuptake is likely to mediate the analgesic effect of these antidepressant drugs in diabetic neuropathy. Fluoxetine, which blocks serotonin uptake, is no more effective than placebo for the relief of pain.", "Seventy patients with primary fibrositis satisfying Smythe's criteria were studied in a 9-week double-blind trial comparing 50 mg amitriptyline with placebo. Fifty-nine patients completed the trial: 27 were treated with amitriptyline, and 32 took a placebo. The patients who received amitriptyline improved significantly in their morning stiffness and pain analog scores at 5 and 9 weeks, compared with baseline scores, whereas no changes were noted in these parameters in the placebo group. Fibrocytic point tenderness did not improve significantly in either of the treatment groups. When compared with the placebo group, the amitriptyline group improved significantly with respect to sleep pattern and patient and physician global assessments. Our data indicate that amitriptyline has some therapeutic benefit in patients with primary fibrositis." ]

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[ "Treatment of adult asthma: controlled double-blind clinical trial of oxitropium bromide.", "Inhaled bronchodilator's in asthma: low or high dose?", "Synergism between ipratropium and theophylline in asthma.", "Home nebulizers: can optimal therapy be predicted by laboratory studies?", "Reduction of nocturnal asthma by an inhaled anticholinergic drug.", "Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A 4-year prospective study.", "Inhaled beclomethasone improves the course of asthma and COPD.", "A comparative study of the bronchodilatating effects of ipratropium and terbutalin inhaled with Monaghan IPPB-M 515 by 19 patients with chronic obstructive airways disease.", "Efficacy and compliance to prolonged Duovent treatment of bronchospasm. Comparison with salbutamol.", "Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis.", "A long-term prospective assessment of home nebulizer treatment.", "Effect of four-week treatment with oxitropium bromide on lung mucociliary clearance in patients with chronic bronchitis or asthma.", "Continuous and on demand use of bronchodilators in patients with non-steroid dependent asthma and chronic bronchitis: four-year follow-up randomized controlled study.", "Comparison of Berodual and salbutamol in asthma: a multicenter evaluation.", "The development of subsensitivity to atropine methylnitrate. A double-blind, placebo-controlled crossover study.", "Terbutaline controlled-release tablets and ipratropium aerosol in nocturnal asthma.", "Density dependence of expiratory flow and bronchodilator response in asthma.", "Comparison of a combination of fenoterol with ipratropium bromide (Duovent) and salbutamol in young adults with nocturnal asthma.", "Comparison of the effect of oxitropium bromide and of slow-release theophylline on nocturnal asthma.", "Oral atropine in the treatment of chronic asthma.", "Comparison of ipratropium bromide and salbutamol in a long-term trial in asthmatic and bronchitic patients in a cold climate.", "Anticholinergic and sympathomimetic combination therapy of asthma.", "Use of ipratropium bromide in asthma. Results of a multi-clinic study.", "Effect of four weeks' high dose ipratropium bromide treatment on lung mucociliary clearance.", "Effects of allergy and age on responses to salbutamol and ipratropium bromide in moderate asthma and chronic bronchitis." ]

[ "Sixteen young adult sufferers from extrinsic paroxysmal asthma with pollen hypersensitivity took part in a therapeutic trial of the synthetic anticholinergic agent oxitropium bromide administered by a metered dose inhaler. The study comprised three 3-week periods. The first, run-in period was carried out to confirm the ability of the patients to maintain a daily record of symptoms. During the second and third periods, the patient received 3 X 2 inhalations of drug or placebo in a cross-over design. The medical staff was blind to the nature of the aerosol (drug or placebo), which was given in random order. The run-in clinical score was high. Asymptomatic days were relatively infrequent and daily drug consumption was high. Functional studies between the cross-over periods showed flow-rate values close to normal, with an increase in residual volume and functional residual capacity. During treatment either with placebo or oxitropium, there was a statistically significant decrease in clinical scores. Results for oxitropium bromide treatment were significantly better than the run-in values (p less than 0.005) and the placebo period (p less than 0.02). There was no significant change in non-trial drug consumption. Functional values showed no difference in terms of flow rate, although oxitropium did cause a significant improvement in the RV/TLC ratio (p less than 0.05). No adverse reactions were reported.", "We studied the effect of regular inhalations of low-dose and high-dose fenoterol and low-dose and high-dose combinations of fenoterol and ipratropium bromide in maintenance treatment of 120 adults with moderately severe asthma. We used a double-blind, randomized, parallel group design comparing 12 weeks of treatment with four regimens: fenoterol, 100 micrograms/dose; fenoterol, 200 micrograms/dose; fenoterol, 50 micrograms; and ipratropium, 20 micrograms/dose in a single inhaler (Berodual) and fenoterol, 100 micrograms and ipratropium, 40 micrograms/dose in a single inhaler (Duovent). During the baseline and active treatment period the patients recorded PEFR in the morning and evening, symptoms and use of a rescue inhaler. Changes in twice daily peak expiratory flow rates or asthma symptoms did not show any significant differences among the four treatment regimens during the 12 weeks compared with the baseline period. Use of the rescue inhaler did not differ among the four groups during the active treatment. The patients' assessment of the efficacy of the active treatment favored the low-dose fenoterol and low-dose combination. More side effects were recorded in the high-dose combination group during the first 4 weeks compared with the other groups. We conclude that in maintenance therapy of chronic asthma high doses of fenoterol alone or in combination with ipratropium bromide offer no clinical advantage over low doses. On the contrary, the low-dose fenoterol and the low-dose combination are better accepted and tolerated by the patients.", "Ipratropium bromide is a bronchodilator whose effect has been compared with beta agonists but not with theophylline. Twelve asthmatics were given four two-week courses of the different combinations of ipratropium (40 micrograms in two puffs), theophylline capsules, and their corresponding placebos in a random, double-blind fashion. There was a significant increase in FEV1 and MMFR 60 minutes after theophylline was administered (p less than 0.05) when measured after one and two weeks of therapy. FEV1 and MMFR were significantly increased (p less than 0.05) 30 and 60 minutes after ipratropium inhalation and this increase was significantly greater when the patient had also been taking theophylline compared with placebo capsules (p less than 0.05). There was no toxicity associated with this combination. The synergism demonstrated may be related to the time sequence of drug administration, mechanical or cellular factors.", "Twenty patients (six severe asthma, 14 chronic obstructive pulmonary disease, COPD) were referred for consideration of domiciliary nebulized treatment. A double blind laboratory assessment demonstrated similar subjective and objective responses to nebulized salbutamol (5 mg), ipratropium bromide (IB) (0.5 mg) or a mixture of these medications in both groups of patients. The patients subsequently self-administered each treatment four times daily for one month. Fourteen patients requested long-term home nebulizer treatment (three salbutamol, four ipratropium bromide, seven mixture), and nine of these had their highest domiciliary peak flow recordings during home nebulizer treatment. However, subjective and objective laboratory assessments did not clearly predict the patients long-term choice of therapy in any case. There was little overall correlation between the laboratory response and the domiciliary response to treatment (Spearman correlation coefficient; subjective score, laboratory vs. home, r = 0.27, P = 0.03; peak flow response 30 min after treatment, laboratory vs. home, r = 0.31, P less than 0.02). The hospital study was also unreliable in predicting side effects during domiciliary nebulizer use. We conclude that prospective laboratory studies are of little value in the assessment of patients for home nebulizer therapy; these assessments must be made by carefully supervised domiciliary trials of nebulized treatment.", "Although the mechanisms of nocturnal asthma are still uncertain, increased vagal cholinergic tone may be contributory factor. To examine this hypothesis, we have studied the effect of an anticholinergic drug, oxitropium bromide, on the early morning fall in peak expiratory flow (PEF) in patients with nocturnal asthma. Eighteen patients (aged 18 to 76 years; seven men) with documented nocturnal asthma were studied in a double-blind randomized cross-over study in which they received either oxitropium bromide (200 micrograms or 400 micrograms) or placebo in a single dose at night for two-week periods. With placebo the mean (+/- SE) fall in PEF (expressed as percentage of evening PEF) was 17.3 +/- 2.0 percent, which was significantly reduced to 10.3 +/- 3.3 percent after oxitropium (400 micrograms) (p less than 0.05; ANOVA). Closer analysis revealed that nine of the 18 patients had responded in a dose-dependent manner, with the mean percentage decreases with placebo, 200 micrograms, and 400 micrograms of oxitropium being 19.1 +/- 3.2, 11.5 +/- 4.4, and 5.0 +/- 4.5 percent, respectively (p less than 0.01 between each treatment). The remaining patients were unaffected by therapy. There were no differences between \"responders\" and \"non-responders\" in terms of age, atopic status, duration of asthma, severity of asthma, or bronchodilator response to albuterol (salbutamol). There were no differences in nocturnal symptoms between periods of treatment, and no side effects were recorded. We conclude that anticholinergic drugs may protect against nocturnal asthma in some patients, indicating the involvement of vagal cholinergic mechanisms.", "To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid.\n A 4-year prospective study.\n Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands.\n The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study.\n During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 micrograms, or ipratropium bromide, 40 micrograms). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 micrograms two times daily.\n Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyperresponsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups.\n Adding beclomethasone, 800 micrograms daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients.", "The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of ipratropium (Atrovent) 0.125 mg x 4 daily was compared to terbutalin (Bricanyl) 5 mg x 4 daily, given to 19 patients with chronic obstructive airways disease (15 with chronic bronchitis, 10 bronchial asthma, 7 pulmonary emphysema) as inhalation therapy with Monaghan IPPB-M 515, during 2 treatment periods of 3 days. The investigation was carried out as a controlled, double-blind, cross-over comparison. The effect of treatment was evaluated by measurement of PEFR, symptom scores, including the side-effects and the use of rimiterol MDI for the treatment of acute attacks. The PEFR values were all higher than the initial values (P less than 0.001) during the period of treatment (08.00-20,30 hrs). The highest values were recorded at 16.30 hrs, these were PEFR + 31.7% for the Atrovent period and PEFR + 28.0% for the Bricanyl period. No statistically significant difference was observed in the PEFR, symptom scores, side-effects and the use of rimiterol during the Atrovent and Bricanyl treatment periods. The authors suggest that Atrovent is a wellsuited alternative bronchodilatator, particularly for patients with tremor, muscle cramp, and \"inner restlessness\" following treatment with a beta 2-stimulator.", "Duovent and salbutamol were compared in 15 patients with stabilized, but partially reversible chronic bronchospasm to verify the persistence of therapeutic effect, bronchodilator efficacy and patient compliance to prolonged treatment with these drugs. Results showed: Clinical efficacy; good protection from bronchospasm. Cough, day-time and nocturnal dyspnoea and the number of additional sprays required were better controlled with Duovent. Activity and bronchodilator efficacy: FVC and even more so FEV1 were sufficiently stable in baseline conditions with negligible variations at the various control times with both drugs, although Duovent was slightly more favourable. Bronchodilator efficacy was maintained more significantly with Duovent compared to salbutamol even after 5 h. Patient compliance: this was better with Duovent, both from the patient's personal opinion and because of the fewer number of daily administrations which the patient received (3 instead of 4).", "Eleven patients with bronchial asthma and 10 with chronic bronchitis were treated over four consecutive 3-day periods, firstly with aerosols either of ipratropium bromide (40 microgram four times a day) or of salbutamol (200 microgram four times daily) by random allocation, then the alternate drug, next by both drugs together, and finally with prednisolone (10 mg three times daily) in addition to both drugs. The effects of these four treatment periods were assessed both clinically and by measuring ventilatory capacity, nitrogen slope and progressive exercise testing. Ipratropium bromide and salbutamol produced approximately equal improvements in both diseases, with salbutamol showing a marginal advantage in patients with asthma. The combination of both drugs together more than doubled the FEV1 change in both groups of patients. The addition of prednisolone to both drugs produced a marginal advantage only in those with asthma.", "Forty-nine patients (15 asthma, mean FEV1/FVC 1.3/2.1; 34 COPD, mean FEV1/FVC 0.7/1.8) were referred for consideration of home nebulizer treatment. All were monitored for 2 weeks while using their usual inhaled treatment followed by 2 weeks using a 'Nebuhaler' spacer to deliver 1 mg of terbutaline and 80 micrograms of ipratoropium bromide (IB) four times daily. They then borrowed a System 22 nebulizer to self-administer salbutamol nebulizer solution (5 mg), IB unit dose vials (0.5 mg) or a mixture of these drugs four times daily for 1 month each. Both asthmatic and bronchitic patients had a significant rise in their mean daily peak flow rate (PFR) during home nebulizer treatment (P < 0.03) and the COPD patients also had a significant PFR rise during Nebuhaler treatment (P = 0.0004). The mean daily peak flow rates (PFR 1 min-1 were: baseline 179, Nebuhaler 195, salbutamol nebulizer 200, IB nebulizer 198, mixed nebulizer 216). Four patients failed to respond subjectively or objectively to either Nebuhaler or nebulizer treatment. Five patients responded well to Nebuhaler treatment and did not proceed to a home nebulizer trial. Eight further patients preferred Nebuhaler to nebulizer treatment or could not tolerate nebulizer treatment (two cases). Thirty-two patients requested home nebulizer treatment for long-term use (nine salbutamol, five IB, 18 mixture). Twenty-seven of these patients had an increased mean daily PFR (compared to their usual therapy) while using their chosen nebulized treatment. The mean increase in PFR for all 32 patients was 191 min-1 (11%).(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of oxitropium bromide on lung mucociliary clearance, pulmonary function and viscoelastic properties of sputum was investigated in 10 asthmatics and 10 chronic bronchitics. A controlled, double-blind, crossover study was performed. Following a baseline (B) measurement the patients were, in a random order, allocated placebo (P) or oxitropium bromide (O; 0.1 mg/puff), administered from metered dose inhalers, which they used for 4 weeks at a dose of 2 puffs t.d.s. This test medication was used in conjunction with their normal medication. At the end of the treatment period the patients were assessed, the treatments were then crossed over and a final assessment made 4 weeks later. The administration of oxitropium bromide resulted in (1) small but statistically significant increases in pulmonary function (less than 10% vs. placebo); (2) increased penetrance of radioaerosol into the lungs (mean +/- SEM alveolar deposition: 35 +/- 3, 26 +/- 3 and 24 +/- 3% for the O, P and B runs respectively; p less than 0.025); (3) no significant change in particle clearance rate from the lungs despite their deeper penetration (mean +/- SEM area under the tracheobronchial clearance curves between 0 and 6 h: 317 +/- 26, 324 +/- 25 and 287 +/- 25%.h for the O, P and B runs respectively; p greater than 0.1); (4) no alteration in sputum production, and (5) no significant changes in apparent viscosity (mean +/- SEM: 640 +/- 162, 446 +/- 79 and 557 +/- 115 mPa.s for the O, P and B runs, respectively; p greater than 0.1) and elasticity (mean +/- SEM: 3,682 +/- 1,383, 1,779 +/- 353 and 2,061 +/- 366 mPa for the O, P and B runs, respectively; p greater than 0.1) of sputum. When the two groups, i.e. the chronic bronchitics and asthmatics, were studied separately, no significant differences in any parameter measured (other than radioaerosol penetrance which was significantly enhanced on oxitropium bromide in chronic bronchitics) were noted between the three assessments.", "A previous two-year study of continuous and on demand bronchodilator therapy in patients with moderate asthma and chronic bronchitis showed a deterioration in lung function in those on continuous therapy.\n A two-year follow-up study was undertaken of patients who had been shown in the previous study to have non-steroid dependent (mild) asthma and chronic bronchitis, in order to investigate the effect of continuous and on-demand treatment with bronchodilator therapy.\n Patients for the study were drawn from 29 general practices in the catchment area of the University of Nijmegen, the Netherlands. A total of 83 patients (27 with asthma and 56 with chronic bronchitis) were selected from a group of 160 patients who had completed the previous two-year bronchodilator trial. During these first two years the selected subjects had been shown to be non-steroid dependent (no rapid decline in lung function and a low number of exacerbations of their condition per year), and they were followed up for another two years of treatment with bronchodilator therapy. At the start of the four-year study, patients were randomly assigned to one of two parallel treatment groups: continuous treatment (dry powder inhalations of either salbutamol 1600 micrograms or ipratropium bromide 160 micrograms daily) or treatment on demand (only during exacerbations or periods of dyspnoea). Outcome parameters were the annual decline in lung function, changes in peak flow rate, bronchial hyper-responsiveness, exacerbation rate, respiratory symptoms and reported health.\n After correction for possibly confounding variables and for regression to the mean, the decline in lung function was 49 ml year in patients taking bronchodilators continuously and 51 ml year in patients using bronchodilators on demand, irrespective of the drug use. Continuously treated patients, whether suffering from asthma or chronic bronchitis, did not differ from patients treated on demand with respect to mean morning peak flow rate, diurnal (and week to week) variation of the peak flow rate, bronchial hyper-responsiveness, exacerbation rate and reported health. There was no difference between the long-term effects of salbutamol and ipratropium.\n Continuous use of bronchodilators over four years in patients with non-steroid dependent asthma or chronic bronchitis does not increase the decline in lung function which had been observed previously in patients with moderate asthma or chronic bronchitis during two years of continuous treatment with bronchodilators.", "A 2-month study was carried out to compare the efficacy and safety of Berodual (B) (Boehringer Ingelheim) and salbutamol (S) in asthma. B is a combined agent with 20 micrograms of ipratropium bromide and 50 micrograms of fenoterol in each metered aerosol puff. Each puff of S contained 100 micrograms of drug. 196 patients were included in the study and received 4 x 2 puffs a day of either B or S. FEV1 and FVC were measured every month, and peak expiratory flow rate (PEFR) 4 times a day, i.e. morning and evening before and after administration of drug. Improvement of PEFR was the same in the two groups. No tachyphylaxis occurred. No difference was observed between the two drugs with regard to heart and respiratory rate, dyspnea and blood pressure. Tremor seemed less frequent with B but this difference was not statistically significant. B achieved the same effects as S though containing less beta-2-agonist agent.", "This is a double-blind, placebo-controlled crossover study designed to assess the effectiveness of nebulized atropine methylnitrate (AMN) with chronic use. We studied 22 patients with asthma, 10 receiving theophylline and inhaled beta-agonists and 12 who were receiving corticosteroids as well. All had demonstrated at least a 15% change in FEV1 either spontaneously or after bronchodilator. Bronchodilator effect was measured serially for 4 h after inhalation of the initial dose and again after 2 wk of four-times-daily use. Significant bronchodilator effect was seen initially with AMN when compared to placebo (p less than 0.01). After 2 wk of use, the bronchodilator effect of AMN was significantly diminished as compared to the initial effect (p less than 0.01) but was still better than placebo (p less than 0.05). Subsensitivity did develop to varying degrees in the patients, but we were unable to identify any clinical parameters that would allow prediction of subsequent subsensitivity. We conclude that the development of subsensitivity to AMN occurs in certain patients with chronic administration but does not reflect a total loss of bronchodilator effect.", "The effect of oral terbutaline (controlled-release [CR] tablets) was compared with that of inhaled ipratropium bromide (aerosol) in 21 patients with nocturnal asthma. In a randomized, double-blind, crossover study, the patients were treated with terbutaline CR 10 mg twice daily, ipratropium 40 micrograms four times daily, and the two drugs in combination. Each treatment was given for 3 weeks. Before the start of the study, the patients participated in a 1-week run-in period. The mean nocturnal decline in peak expiratory flow rate (PEFR) was 29% in the run-in period and was reduced to 22% in the terbutaline CR period, 27% in the ipratropium period, and 23% in the period with the combination of the two drugs. The mean night PEFR was significantly (P < 0.05) higher in the period with terbutaline CR, as compared with the period with ipratropium. The mean morning PEFR was also highest in the terbutaline CR period. The mean evening PEFR was significantly (P < 0.05) higher during treatment with terbutaline CR alone and with the combination, as compared with treatment with ipratropium alone. Treatment with terbutaline CR alone or the combination was preferred by as many patients as was treatment with ipratropium alone. When present, adverse reactions were judged to be mild or moderate. Treatment with terbutaline CR alone and the combination significantly improved the evening and night PEFR, as compared with treatment with ipratropium alone.", "Change in the magnitude of density dependence of the maximal expiratory flow (D/MEF) following inhalation of isoproterenol was used as a test for predicting the long term response to isoproterenol vs atropine in 24 adult patients with longstanding asthma. Eleven subjects showed a decrease in D/MEF manifested by increase in volume of isoflow (VisoV) and/or decrease in Vmax50 Helox/air following isoproterenol inhalation (group 1). Thirteen subjects manifested an opposite response (group 2). Atropine sulphate (0.08 mg/kg) and isoproterenol hydrochloride (2.5 mg) were then administered by inhalation, each four times a day for seven days in a randomized double-blind cross over fashion to all subjects. One of group 1 but ten of group 2 subjects had a greater subjective and objective improvement with atropine than with isoproterenol (P less than .005). An increase in D/MEF following isoproterenol can be used as a test to predict a better response to atropine than to isoproterenol over a one week period. Such a response occurs in almost half of the adult chronic asthmatic patients. The results are consistent with a preferential dilatation of the large airways by atropine.", "In a randomized, double-blind, double-dummy, crossover study consisting of two 1-month periods with a 2-week 'run-in' we compared the effects of a combination of fenoterol with ipratropium bromide (Duovent, Boehringer Ingelheim) and salbutamol administered by standard metered dose inhalers in conventional dosage in young adults with nocturnal asthma. Seventeen patients were studied, all were aged between 19 and 35 years and showed 'morning dip' associated with nocturnal symptoms of cough, wheeze and breathlessness. They recorded morning and evening peak flows and symptoms of nocturnal asthma on diary cards. Over the 10 weeks of the study there was no difference between Duovent and salbutamol in any of the parameters measured.", "The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow-release theophylline preparation upon nocturnal asthma were compared in a placebo-controlled double-blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t.i.d. (6 subjects) whereas 11 received theophylline at 300 mg b.i.d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage.", "Six adult patients with chronic asthma were treated with oral atropine sulfate 0.5 mg or placebo four times a day in a double-blind, crossover trial lasting eight weeks. Subjects returned at weekly intervals for spirometry and clinical evaluation. The baseline pulmonary functions did not differ significantly between the atropine and placebo periods. The only side effects noted were slight dryness of the mouth in three patients. The three patients who complained of mouth dryness felt that they were better while they were taking oral atropine in that they had fewer acute episodes of asthma. The administration of 0.5 mg oral atropine four times a day is ineffective in improving baseline pulmonary functions in chronic asthmatics, although it may decrease the incidence and severity of acute asthmatic episodes.", "nan", "The role of the anticholinergic drug, ipratropium bromide, in maintenance antiasthmatic therapy was evaluated in a double-blind crossover trial of three bronchodilator regimens: (1) inhaled ipratropium, placebo, and oral oxtriphylline; (2) inhaled fenoterol, placebo, and oral oxtriphylline; and (3) both inhaled ipratropium and fenoterol plus oral oxtriphylline. Twenty-two asthmatics were treated with all three regimens, each for 1 mo, allocated in random sequence. On the first and last treatment days of each month, spirometric measurements were performed before and 0.5, 1, 2, 3, 4, and 6 hr after administration of the test drugs. On the first treatment day of each month, all regimens produced significant bronchodilatation at 30 min after dose, an improvement that declined between 3 and 6 hr after dose. After continuous administration for 1 mo the two combinations employing fenoterol showed a decline in bronchodilator responsiveness from the initial treatment day, measured as the level of response (V50) or duration of response (FEV1, VC). Ipratropium plus oxtriphylline showed no such decline, suggesting the development of tolerance to long-term administration of fenoterol. Overall benefit at the end of 1 mo, measured as the area under the curves of FEV1, VC, or V50 vs time after dose, was greatest for the triple drug regimen. There were no differences in heart rate, blood pressure response, or side effects among the three treatments. It is concluded that when the anticholinergic drug ipratropium is administered concurrently with an inhaled beta 2 agonist and an oral theophylline derivative, increased bronchodilatation occurs with no detectable additional side effects.", "A multi-center, double-blind, 90-day study compared an ipratropium bromide metered-dose inhaler (40 microgram four times a day) with a metaproterenol metered-dose inhaler (1,500 micrograms four times a day) in 164 patients with asthma; of the 144 patients who completed the study, 71 received ipratropium and 73 received metaproterenol. Our results suggest that both drugs were equally effective bronchodilators. Although the shape of the pulmonary function response curves suggested that ipratropium has different bronchodilator kinetics than metaproterenol (in that it has a slower onset of action and a more prolonged duration), comparison of the areas under the curves for the two drugs showed that there was no statistical difference between ipratropium or metaproterenol. The only significant side effects noted with ipratropium were cough and exacerbation of symptoms; no anticholinergic side effects were noted.", "In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 micrograms three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity.", "The bronchodilating responses to 400 micrograms salbutamol and 80 micrograms ipratropium bromide were studied in 188 patients with chronic bronchitis (n = 113) or asthma (n = 75) and mild to moderate airflow obstruction (forced expiratory volume in one second (FEV1) above 50% but below 2 SD of predicted value) in a crossover study on two days a week apart. Both the patients with asthma and the patients with chronic bronchitis varied considerably in their responses to the salbutamol and the ipratropium bromide. The mean increase in FEV1 in the subjects with asthma was higher after salbutamol (0.371 or 18% of the prebronchodilator value) than after ipratropium bromide (0.26 1 or 13%). In chronic bronchitis there was no difference between the increase in FEV1 after salbutamol (0.161 or 7%) and after ipratropium bromide (0.191 or 8%). When patients were categorised into those with a better response to salbutamol 400 micrograms and those with a better response to ipratropium bromide 80 micrograms, patients with chronic bronchitis responded better in general to ipratropium bromide whereas asthmatic patients responded better to salbutamol. The response pattern was also related to allergy and age, allergic patients and patients under 60 being more likely to respond better to salbutamol 400 micrograms than non-allergic patients and older patients, who benefited more from ipratropium bromide 80 micrograms. The response pattern was not related to sex, smoking habits, lung function, bronchial reactivity, respiratory symptoms, or number of exacerbations during the preceding year." ]

[ "15502112", "15383189", "18186995", "17166990", "22015542", "21942354" ]

[ "Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma.", "Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma.", "Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?", "Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma.", "Budesonide/formoterol maintenance and reliever therapy in primary care asthma management: effects on bronchial hyperresponsiveness and asthma control.", "A comparison of budesonide/formoterol maintenance and reliever therapy versus conventional best practice in asthma management in Spain." ]

[ "Asthma control is improved by combining inhaled corticosteroids with long-acting beta2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting beta2-agonist (SABA) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy, thereby reducing exacerbations. In this double-blind, randomized, parallel-group study, 2,760 patients with asthma aged 4-80 years (FEV1 60-100% predicted) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 microg twice a day (bud/form + SABA) or bud 320 microg twice a day (bud + SABA) or bud/form 80/4.5 microg twice a day with 80/4.5 microg as-needed (bud/form maintenance + relief). Children used a once-nocte maintenance dose. Bud/form maintenance + relief prolonged time to first severe exacerbation (p < 0.001; primary endpoint), resulting in a 45-47% lower exacerbation risk versus bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form maintenance + relief also prolonged the time to the first, second, and third exacerbation requiring medical intervention (p < 0.001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.", "This study evaluated the efficacy and safety of a novel asthma management strategy--budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy)--compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma.\n This was a 12-month, randomised, double-blind, parallel-group study. Symptomatic patients with asthma (n = 1890; mean age 43 years [range 11 years-80 years], mean baseline forced expiratory volume in 1 s [FEV(1)] 70% of predicted, mean inhaled corticosteroid [ICS] dose 746 microg/day) received either budesonide (160 microg, 2 inhalations twice daily) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol (160/4.5 microg, 2 inhalations once daily) with additional inhalations of budesonide/formoterol 160/4.5 microg as needed. Time to first severe exacerbation (hospitalisation/emergency room [ER] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [PEF] to < or = 70% of baseline on 2 consecutive days) was the primary outcome variable.\n A total of 1890 patients were randomised, of whom 1563 (83%) had severe asthma. The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy (p < 0.001) compared with a higher dose of budesonide. The risk of having a severe exacerbation was 39% lower with budesonide/formoterol single inhaler therapy compared with budesonide (p < 0.001). The number needed to treat to prevent one severe exacerbation per year with budesonide/formoterol compared with budesonide was 5. The budesonide/formoterol group had 45% fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group (p < 0.001). Budesonide/formoterol patients had fewer hospitalisations/ER treatments (15 vs 25 events, respectively [descriptive statistics]) and fewer treatment days with systemic steroids (1776 days vs 3177 days, respectively [descriptive statistics]) compared with budesonide patients. Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients (0.90 vs 1.42 inhalations/day; p < 0.001). The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group (466 microg/day vs 640 microg/day). Over the 12-month study period, the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60% of days. Overall, budesonide/formoterol single inhaler therapy gave 31 more asthma control days (a night and day with no asthma symptoms and no as-needed medication use) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide. Both treatments were well tolerated.\n Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler, demonstrating a high level of efficacy in patients with moderate to severe asthma.", "Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success.\n To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids.\n Randomised, parallel group, open-label trial.\n Forty-four general practices in Nottinghamshire.\n Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose.\n Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified.\n Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.", "A fixed combination of long-acting beta(2)-agonists (LABA) plus inhaled corticosteroids (ICS) has never been proven to reduce asthma exacerbations vs ICS alone in children. This 12-month, double-blind, randomized study in 341 children (age range, 4 to 11 years) with asthma uncontrolled on ICS investigated whether a novel regimen using budesonide/formoterol for maintenance and reliever therapy (Symbicort maintenance and relief therapy [SMART]) [Symbicort; AstraZeneca R&D, Lund, Sweden] could reduce exacerbations.\n Patients received SMART (budesonide/formoterol 80/4.5 microg qd maintenance plus additional inhalations for symptom relief), budesonide/formoterol 80/4.5 microg qd for maintenance (fixed combination), or higher-dose budesonide 320 microg qd (fixed-dose budesonide). Blinded as-needed medication (terbutaline 0.4 microg) was provided in both fixed-dose groups.\n SMART prolonged the time to first exacerbation vs fixed-dose budesonide (p = 0.02) and fixed-dose combination (p < 0.001). Rates of exacerbation requiring medical intervention were reduced by 70 to 79% with SMART vs fixed-dose budesonide and fixed-dose combination (0.08/patient vs 0.28/patient and 0.40/patient, respectively; both p < 0.001). Mild exacerbation days and awakenings were significantly lower with SMART; yearly growth improved by 1.0 cm vs fixed-dose budesonide (p < 0.01).\n The SMART regimen using budesonide/formoterol for both maintenance and as-needed symptom relief reduces the exacerbation rate compared with both fixed-dose combination and higher fixed-dose ICS alone in children with asthma.", "The management of asthma has changed since the introduction of budesonide/formoterol (Symbicort®) as both maintenance and reliever therapy (SMART). SMART and its effects on bronchial hyperresponsiveness (BHR) have not been studied in primary care.\n To compare the effects of SMART and guideline-driven usual care (UC) on BHR and clinical asthma severity in primary care practice.\n Patients with mild-to-moderate stable asthma were randomised to receive SMART treatment (n=54) (budesonide/formoterol 80/4.5 μg Turbuhaler®, two puffs once daily and extra inhalations as needed) or UC treatment (n=48) for 12 months. Diary data, Asthma Control Questionnaire scores, forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) measurements were collected during run-in and after 1, 3, 6, and 12 months of treatment. BHR, measured as the dose of histamine provoking a fall in FEV1 of 20% (PD20-histamine), was determined at randomisation and after 12 months.\n One hundred and two patients with asthma participated in the study. The change in PD20-histamine during the study was not significantly different between the SMART and UC groups (p=0.26). The mean inhaled corticosteroid (ICS) dose was 326 μg beclomethasone dipropionate (BDP) equivalents/day (95% CI 254 to 399) with SMART, which was significantly lower (p<0.0001) than the mean ICS dose with UC treatment (798 μg BDP equivalents/day (95% CI 721 to 875). Morning and evening PEF values increased significantly with SMART treatment compared with UC; FEV1, symptoms and asthma control did not differ.\n Despite a 59% lower dose of ICS, BHR and other clinical outcomes remained stable during SMART treatment while PEF values improved.", "To study the effectiveness and safety in a real-life setting of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy® (Symbicort SMART®), a simplified management approach with one inhaler, compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma.\n Open-label randomized controlled parallel-group trial, 6-month treatment.\n A total of 654 adult patients, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting β(2)-agonist.\n Time to first severe asthma exacerbation and number of severe asthma exacerbations.\n No difference between groups was seen in time to first severe exacerbation (p = .2974). Exacerbation rates were low in both groups. A total of 22 patients in the Symbicort SMART group experienced a total of 24 severe asthma exacerbations, and 31 patients in the CBP group experienced a total of 34 severe asthma exacerbations (annual rate 0.16 vs. 0.22, p = .2869). The mean daily dose of ICS expressed in beclomethasone dipropionate equivalent was significantly lower in the Symbicort SMART group (including as-needed use) versus the CBP group (799 μg vs.1184 μg; p < .001). Mean scores in Asthma Control Questionnaire, five-question version, improved significantly in the SMART group compared with the CBP group (p = .0292). Symbicort SMART and CBP were equally well tolerated. The mean drug cost per patient per 6 months was lower for the patients in the SMART group compared with patients receiving CBP (€295.32 vs. €387.98, p < .0001).\n A simplified regimen using budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and lower drug costs." ]

[ "3350206", "16169580", "3139415" ]

[ "Flavoxate hydrochloride for urinary urgency after pelvic radiotherapy: comparison of 600 mg versus 1200 mg daily dosages.", "A phase II study to evaluate WF10 in patients with late hemorrhagic radiation cystitis and proctitis.", "Post-irradiation cystitis improved by instillation of early placental extract in saline." ]

[ "This preliminary communication reports on a non-randomized pilot type trial of 34 females with urgency after pelvic radiotherapy who were treated with flavoxate hydrochloride for 4 weeks. A dosage of 600 mg/day was given to 21 patients and 1200 mg/day to 13 patients. Clinically, both regimens achieved comparable results. Urodynamically (first desire volume, bladder capacity and pressure at capacity) treatment with 1200 mg/day was significantly superior to 600 mg/day. Both schedules were equally well tolerated by patients and no treatment interruption occurred. A randomized double-blind trial comparing 600 and 1200 mg/day flavoxate hydrochloride is currently underway the results of which will be reported in due course.", "To evaluate efficacy and safety of WF10 (TCDO iv solution) therapy in patients with late hemorrhagic radiation cystitis and proctitis in a long-term follow up.\n From February 1999 to July 2001, 30 symptomatic patients with endoscopically confirmed grade 2 and 3 late hemorrhagic cystitis (n = 16) and proctitis (n = 14) were treated with WF10. The dose was 0.5 ml/kg BW, diluted in 250 ml 5%D/W, administered by intravenous infusion over 2 h, 5 consecutive days, every 3 weeks for 2-4 cycles, combined with standard therapy. The patients were clinically followed up every 3 weeks for 3 months, then every 3 months for 1 year and then every 3-6 months. The study endpoints were immediate response with improvement to Grade 0-1 within 3 months and the incidence of recurrence to Grade > or =2 during the follow up time.\n After completion of the WF10 therapy, 14 cystitis patients (88%) had improved to grade 0-1 hematuria, and 14 proctitis patients (100%) had improved in bleeding per rectum to grade 0-1 within 3 months. The median follow up time was 51 months. During the follow up period, among the responders, 4 cystitis patients (28%) had recurrent hematuria of grade 2 and two proctitis patients (14%) had recurrent bleeding per rectum of grade 2 and 3. No treatment toxicity was observed.\n The WF10 therapy combined with conventional treatment is simple and safe with long-term efficacy in the treatment of late hemorrhagic radiation cystitis and proctitis.", "21 patients with chronic cystitis due to irradiation therapy for carcinoma of the cervix had symptomatic and cystoscopic improvement from instillations of early placental extract in saline. There was a statistically significant difference between these patients and a control group." ]

[ "6418300", "13686065", "3318990", "12744577", "13030821", "21206808", "4729877", "7850397", "10492856", "10924665", "6039994", "21927109", "11940967", "22058556", "22058544" ]

[ "Electroconvulsive therapy: results in depressive illness from the Leicestershire trial.", "E.C.T. in schizophrenia.", "The efficacy of electroconvulsive therapy in the treatment of schizophrenia. A comparative study.", "A controlled trial of modified electroconvulsive therapy in schizophrenia in a Nigerian teaching hospital.", "A comparison between unidirectional current nonconvulsive electrical stimulation given with Reiter's machine, standard alternating current electro-shock (Cerletti method), and pentothal in chronic schizophrenia.", "Electroconvulsive therapy in Lorazepam non-responsive catatonia.", "Unilateral versus bilateral ECT in schizophrenia.", "An exploratory evaluation of ECT in haloperidol-treated DSM-IIIR schizophreniform disorder.", "Continuation ECT in treatment-resistant schizophrenia: a controlled study.", "Effects of stimulus intensity on the efficacy of bilateral ECT in schizophrenia: a preliminary study.", "Daily administration of unilateral ECT.", "Role of ect phenothiazine combination in schizophrenia.", "Reevaluation of ECT in Schizophrenia: Right Temporoparietal versus Bitemporal Electrode Placement.", "Evaluation of cognitive effects of ect (preliminary observations).", "Ect-chlorpromazine combination compared with chlorpromazine only in schizophrenia." ]

[ "Electroconvulsive therapy was investigated in a double blind trial. Altogether 186 clinically selected patients were referred to the trial, but 48 of these did not participate. According to the present state examination, 95 of the remaining 138 patients fell into one of the classes of major depression. Patients were randomly allocated to a course of real or simulated electroconvulsive therapy. Treatment was given twice a week with a maximum of eight treatments. On the Hamilton depressive rating scale the improvement in the group given real treatment was significantly greater than that in the group given simulated treatment both at two weeks (p = 0.014) and at four weeks (p = 0.0001). At follow up at 12 and 28 weeks there was no difference between the treatment groups. At the end of the four week trial consultants, who were blind to the allocation of treatment, rated the patients who had received real treatment as having made a significantly greater improvement than the patients who had received simulated treatment (p less than 0.00005). Further analysis showed that electroconvulsive therapy was effective in depression associated with delusions and in depression associated with retardation.", "nan", "The efficacy of ECT was investigated in a double-blind trial. Twenty-two patients with schizophrenia received trifluoperazine and were randomly allocated to receive eight real or eight simulated ECTs. In the first eight weeks, the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale. However, the groups showed no significant differences from the twelfth week onwards. The superiority of real ECT was not confirmed at the end of six months.", "The efficacy of ECT in the treatment of Schizophrenia was investigated in a double blind controlled trial. The ICD-10 criteria for Schizophrenia were fulfilled by the 20 patients who entered the trial. Consecutive individuals who satisfied the inclusion criteria were randomly allocated to a course of (bilateral) six real or simulated ECTs each as applicable. Sixteen patients completed the ECT treatment and 20 weeks follow up period. Analysis of measures of clinical change (BPRS and SANS Scores) showed that both groups of patients improved, but the improvement of patients receiving ECT was not significantly greater than that of the control group.", "nan", "To compare the efficacy of electroconvulsive therapy (ECT) with risperidone in the treatment of lorazepam non-responsive catatonia.\n Inpatients with non-affective catatonia (n= 18) non-responsive to at least five-day trial of lorazepam (6-8 mg/day) were randomised into two groups in a double blind randomised design. Written informed consent was obtained. Four were dropped from the trial as they were found to have depressive catatonia. One group received true ECT (thrice weekly, n=8) plus oral placebo while the other received sham ECT plus risperidone (4-6 mg/ day). Bush-Francis Catatonia Rating Scale (BFCRS) was administered twice weekly to assess improvement in catatonic symptoms over a period of three weeks. The two groups were compared using two-way RMANOVA.\n BFCRS scores reduced markedly over treatment course and this reduction was more profound in the ECT group (p=0.035). Shorter the duration of illness greater was the response (lower scores of BFCRS).\n Superior clinical efficacy of ECT over neuroleptics in catatonia is confirmed by this randomized clinical trial.", "nan", "In a double-blind, prospective study, 30 consecutive treatment-naive adult men with first-onset psychosis and DSM-IIIR provisional schizophreniform disorder (without good prognostic features) were randomized into true electroconvulsive therapy (ECT) and sham ECT groups. Both groups received haloperidol in a fixed dose of 15 mg at night. The ECT schedule comprised six bilateral, sinusoidal wave treatments administered on alternate days, thrice a week. Weekly ratings for the first 6 weeks showed an absence of significant difference between the groups in the number of patients responding and in the rate of attenuation of psychosis; severity of depression, while less in the true ECT group after the first 3 weeks, did not differ between the groups at any subsequent time point. Clinical ratings were repeated at 6 months, and social functioning was assessed; again, no group differences emerged. It is concluded that ECT does not meaningfully improve response in unselected schizophreniform disorder that is treated with an adequate dose of neuroleptic.", "In patients with treatment-resistant schizophrenia (TRS), this study compared the efficacy of continuation treatment with flupenthixol alone, continuation electroconvulsive therapy (ECT) alone, and combined continuation ECT and flupenthixol. One hundred fourteen TRS patients received acute treatment (Phase I) with bilateral ECT and flupenthixol (12-24 mg/day). Fifty-eight patients met remitter criteria, including clinical stability during a 3-week stabilization period, and were eligible for the continuation treatment study (Phase II). Fifty-one patients enrolled in the single-blind Phase II continuation trial, and were randomized to the three treatment groups. The duration of the Phase II study was 6 months. Assessments of outcome included the Brief Psychiatric Rating Scale, Global Assessment of Functioning, and the Mini-Mental State Examination. Forty-five patients either relapsed or completed the Phase II study, and six patients dropped out. Among completers, 6 of 15 (40%) patients relapsed in the combined continuation ECT and flupenthixol group. In both the group treated with continuation ECT alone and that with flupenthixol alone, 14 of 15 (93%) patients relapsed. Analyses of intent-to-treat and completer samples demonstrated a marked advantage for the combination treatment condition in relapse prevention. Furthermore, all eight patients who received maintenance ECT combined with neuroleptic medication (Phase III study) maintained therapeutic benefits during the follow-up period of 3-17 months after the continuation treatment study. Among TRS patients who respond to acute combination treatment with ECT and neuroleptic therapy, continuation of this combination treatment is more effective in relapse prevention than use of ECT or neuroleptic therapy alone.", "This preliminary study examined the effects of electrical stimulus intensity on the speed of response and efficacy of bilateral electroconvulsive therapy (ECT) in the treatment of schizophrenia.\n Sixty-two patients with schizophrenia received combination treatment with bilateral ECT and flupenthixol. Using a randomized, double-blind design, the effects of three dosages of the ECT electrical stimulus were examined. Patients were treated with a stimulus intensity that was just above seizure threshold, two-times threshold, or four-times threshold. Assessments of outcome used the Brief Psychiatric Rating Scale, Global Assessment of Functioning, and the Mini-Mental State Exam.\n Thirty-three of sixty-two patients met remitter criteria, including maintaining improvement over a 3-week stabilization period. The dosage groups were equivalent in the number of patients who met remitter criteria. The low-dose remitter group (n = 11) received more ECT treatments and required more days to meet remitter status than both the twofold (n = 11) and fourfold remitter groups (n = 11). There was no difference among the groups in change in global cognitive status as assessed by the Mini-Mental State Exam.\n This preliminary study indicates that treatment with high-dosage bilateral ECT speeds clinical response in patients with schizophrenia. There may be a therapeutic window of stimulus intensity in impacting on the efficacy of bilateral ECT, which needs further study. A more sensitive battery of cognitive tests should be used in future research.", "nan", "A prospective double blind study was conducted to evaluate the role of E.C.T. in schizophrenia. Before the start of the trial patients were kept on chlorpromazine in adequate dosage for 30 days. Those who showed fifty percent or more improvement during this period were excluded. All patients were given eight modified or simulated E.C.T.s. The patients were followed up for one month. E.C.T. did not show any added advantage over chlorpromazine either initially or during short term follow-up.", "Two groups of schizophrenic patients received either bitemporal or right temporoparietal electroconvulsive therapy (ECT), both without anesthesia. Each patient received six treatments, the first three at 2-day intervals and the next three at 4-day intervals. Psychiatric evaluations and cognitive tests done at baseline, and 7 and 20 days after therapy, found similar degrees of improvement and similar effects on memory in both groups, with improvement in 40% and impairment in 30% of the patients. Subjective forgetfulness is more often experienced by the patients who receive bilateral ECT.", "The aim of present double blind controlled study is to evaluate the effects of ECT in Schizophrenia and Depression. 20 depressed and 20 schizophrenic patients of either sex, in the age group 18 to 65 years fulfilling the inclusion and exclusion criteria were taken for study. The psychiatric evaluations were carried out before the treatment, and at the end of 3, 6, 8 and 10 treatments. Cognitive test battery was administered before the treatment and 48 hours after the last treatment. No Post ECT cognitive deficit was observed on the test battery though some patients did complain of forgetfulness subjectively.", "Forty-four hospitalized schizophrenic patients, 22 in each of two groups, were treated for a period of 6 weeks with either EGT-GPZ combination or CPZ alone. Ratings on RP scale (Rockland and Pollin, 1S65) showed that the KGT-receiving group was significantly better en several measure at second week and also had an earlier onset of beneficial response on \"Affect and Mood.\" However, at the end of 6 weeks, these differences disappeared and on clinical Global Impression of Improvement the two groups did not differ significantly. The implications are discussed." ]

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[ "Clonidine and opiate receptor antagonists in the treatment of heroin addiction.", "Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance.", "Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin.", "Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial.", "Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients.", "Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital.", "[Methadone, clonidine and levomepromazine in the treatment of opiate abstinence syndrome: double-blind clinical trial in heroin-addicted patients admitted to a general hospital for organic pathology].", "Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification.", "[Clonidine in opiate withdrawal syndrome].", "Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal.", "Clonidine in outpatient detoxification from methadone maintenance.", "[Tizanidine in the treatment of acute withdrawal symptoms in heroin dependent patients].", "Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone.", "Clonidine in heroin withdrawal syndrome: a controlled study in India.", "Use of qigong therapy in the detoxification of heroin addicts.", "Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal.", "The association carbamazepine-mianserin in opiate withdrawal: a double blind pilot study versus clonidine.", "Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.", "A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.", "Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal." ]

[ "Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists. One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with (a) clonidine only, (b) clonidine and naltrexone, (c) clonidine and naloxone, and (d) placebos. Treatment results, emotional and behavioral changes, and involvement in psychosocial programs were evaluated after a 6-month follow-up. Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms, there was, in the group of patients treated with clonidine and naltrexone together, a low percentage of catabolites in urine and an improvement in mood and family relationships. Furthermore, the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs, and even their relatives demonstrated more interest in the recovery program. A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone.", "A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients.", "The efficacy of a rapid detoxification schedule (8 to 10 days) with clonidine or methadone was evaluated in 30 patients addicted to heroin. The dose of study drug was preestablished according to the subject's weight and the amount of opioid consumption, and the total daily dose was reduced by approximately 15% during the study. All subjects completed the detoxification program and stayed in the hospital for at least 12 days. Clonidine and methadone therapies proved to be highly effective. There was a marked reduction in anxiety during opioid detoxification, although subjects' experiences differed according to the drug used. On the day of discharge, subjects who had received methadone still had attenuated withdrawal symptoms, whereas there were no such symptoms in the clonidine group. Muscular aching, flatulence, and daily drowsiness were more common among subjects in the methadone group, while subjects in the clonidine group had more sleep disturbances and weeping. Syncopal episodes and bradycardia occurred more frequently in the clonidine group.", "The efficacy of clonidine, methadone, and guanfacine in rapid detoxification of heroin inpatients was assessed in a randomized controlled clinical trial. Signs and symptoms of abstinence and of side effects were analysed in 90 heroin addicts successfully completing a 12-day inpatient trial. All patients fit DSM-III criteria for opioid dependence, the age range being 18 to 36 years. All three drugs were effective in controlling abstinence; however, the course of abstinence was different in the methadone group as compared to the adrenergic agonists, the latter showing limitations in their ability to suppress withdrawal manifestations. While mean number of withdrawal signs and symptoms was significantly lower during days 2 to 5 in the methadone group (p less than 0.01), adrenergic agonists were slightly more effective at the end of the trial. Incidence of side effects was closely related to the dose administered. Hypotensive action of adrenergic agonists was more marked in orthostatic position. The present results suggest that methadone is superior to adrenergic agonists. Between these drugs clonidine appears to be less effective than guanfacine in controlling some withdrawal manifestations, and causes more side effects, mainly of cardiovascular nature.", "In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms.", "Twenty eight opiate addicted inpatients who had been stabilised on methadone took part in a double-blind randomised trial of clonidine and lofexidine (14 on each treatment) for opiate detoxification: clonidine or lofexidine dosage was titrated according to symptoms. The course of withdrawal symptoms was very similar with both treatments, representing an appreciable suppression of symptoms when compared with experiences of sudden methadone withdrawal, but lofexidine resulted in significantly less hypotension and adverse events. These results suggest that lofexidine is a valuable drug for opiate detoxification and may be more acceptable to patients wishing to withdraw from opiates.", "nan", "This open study compares an accelerated 5-day lofexidine regimen with orthodox 10-day lofexidine and methadone regimens in the treatment of opiate withdrawal in 61 polysubstance abusing opiate addicts. Significant differences in levels of withdrawal symptoms were found on days 11, 13-15 and 17-20, symptoms resolving most rapidly in the 5-day lofexidine treatment group, whilst withdrawal responses in the 10-day lofexidine treatment group were intermediate between the 5-day lofexidine and standard methadone treatment conditions. When the two lofexidine regimens were separately compared with methadone the 5-day lofexidine treatment was significantly more effective on day 10, 11 and 13-20, whilst the 10-day lofexidine treatment was not significantly different from methadone. There were no significant differences in rates of completion of detoxification between the three treatments. Both the lofexidine treatment regimens had a similar effect on blood pressure. Five patients experienced side effects which resolved with dose reduction, all remaining in the study. An accelerated 5-day lofexidine regimen may attenuate opiate withdrawal symptoms more rapidly than conventional 10-day lofexidine or methadone treatment schedules without exacerbating hypotensive side effects.", "nan", "This study compares the clinical responses to methadone and lofexidine in the treatment of opiate withdrawal in 86 polydrug-abusing opiate addicts, using a randomised double-blind study design. The lofexidine treatment more severe symptoms from day 3 to 7 and again on day 10 (the last day of treatment), but thereafter both groups showed a similar progressive symptom decline. There was no significant difference in rates of treatment completion. Both treatments had similar effects on blood pressure. Lofexidine is broadly clinically equivalent to methadone, and appears to be a non-opiate treatment of opiate withdrawal without serious limiting hypotensive side effects.", "Inpatient narcotic detoxification with clonidine hydrochloride has been used since 1978. Outpatient withdrawal, potentially more useful, has not been adequately studied. This report describes a double-blind random assignment of 49 methadone hydrochloride-maintained patients whose dose had been lowered to 20 mg. Twenty-five were detoxified using methadone at 1-mg decrements, 24 by abrupt substitution with clonidine. Approximately 40% of both groups achieved successful detoxification, with one third maintaining abstinence over the subsequent six months. The groups were also largely equivalent on withdrawal symptoms, but the clonidine group experienced symptoms in the first half of the study and the methadone group in the second half. Clonidine appears to be a safe and efficacious outpatient treatment for opiate withdrawal, although the results were less favorable than those obtained in open or inpatient studies.", "One of the treatment alternative of withdrawal symptoms of patients suffering from opiate dependence is to apply the clonidine in combination or itself. This remedy is not in commercial trade in our country. It is expectable according to the recent data analysing the effects of the alfa2 adreneregic agonist tizanidine that tizanidine has the similar protective effect as clonidine with the resembling target point. Based on this theory a research was done, in the course of which the i.v. heroin users who presented themselves at the Drug Outpatient Department of Buda between 1.10.1998-8.01.1999. were divided into two groups. The groups had got the usual detoxification treatment, but in the experimental group tizanidine were given in 3 x 8 mg/day dose too. Sixteen patients were in the tizanidine group, 10 patients were in the control group. The patients estimated the intensity of 7 symptoms of withdrawal (sweating, nervousness, insomnia, tremor, diarrhoea, muscle pain, drug craving) on a subjective scale day by day. The analysis showed that the tizanidine treatment decreased the intensity of the withdrawal symptoms in every symptom type examined. The ten days long acute withdrawal period were accomplished by all of the patients, but in the short course of the following (mean 9 and 11 weeks in the treated and the control groups respectively) there were three relapses in each group (3/16 in the treated and 3/10 in the control).", "This paper reports results from the first controlled trial of opioid withdrawal treatment in the UK using lofexidine in a prison setting. Seventy-four opioid dependent male inmates at a Southern England prison were randomised to receive either methadone (the standard prison treatment) or lofexidine using a randomised double-blind design. No significant statistical difference between the treatment groups was found in relation to the primary variable of severity of withdrawal symptoms (effect size=0.12). No discernible difference was found in the sitting blood pressure or heart rate of the two groups during the trial. These results provide support for the use of lofexidine for the management of opioid detoxification in the prison setting.", "nan", "Qigong is a traditional Chinese health practice believed to have special healing and recovery power. Little scientific documentation was found on qigong and its effectiveness, and no literature was found on qigong as a treatment of substance addiction.\n To explore the effectiveness of qigong therapy on detoxification of heroin addicts compared to medical and nonmedical treatment.\n Participants were randomly assigned to 1 of 3 groups: qigong treatment group (n = 34), medication group (n = 26), and no-treatment control group (n = 26).\n Eighty-six male heroin addicts, aged 18 to 52 years, who met the substance-dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, with a history of heroin use from .5 to 11 years. All were residents at a mandatory drug-treatment center in the People's Republic of China.\n The qigong group practiced Pan Gu qigong and received qi adjustments from a qigong master daily. The medication group received the detoxification drug lofexidine-HCl by a 10-day gradual reduction method. The control group received only basic care and medications to treat severe withdrawal symptoms.\n Urine morphine test, electrocardiogram, Hamilton Anxiety Scale, and a withdrawal-symptom evaluation scale were applied before and during the 10-day intervention.\n Reduction of withdrawal symptoms in the qigong group occurred more rapidly than in the other groups. From day 1, the qigong group had significantly lower mean symptom scores than did the other groups (P <.01). Both the qigong and medication groups had much lower anxiety scores than did the control group (P<.01), and the qigong group had significantly lower anxiety scores than did the medication group (P<.01). All subjects had a positive response to the urine morphine test before treatment. Fifty percent of the qigong group had negative urine tests on day 3, compared to 23% in the control group and 8% in the medication group (P <.01). By day 5 of treatment, all subjects in the qigong group had negative urine tests, compared to day 9 for the medication group and day 11 for the control group.\n Results suggest that qigong may be an effective alternative for heroin detoxification without side effects, though we cannot completely eliminate the possibility of the placebo effect from the current study.", "Lofexidine is an analogue of clonidine, an agonist at the alpha 2 noradrenergic receptor. Reports from preliminary open studies have suggested that it may be at least as effective as clonidine in the management of opiate withdrawal, and without the same limitation of postural hypotension. We report on a randomised double-blind comparison of lofexidine versus clonidine in the treatment of heroin withdrawal. A total of 80 hospitalized heroin addicts were randomly assigned to treatment with lofexidine or clonidine during in-patient opiate withdrawal. Maximum daily doses were 1.6 mg for lofexidine and 0.6 mg for clonidine. There was marked diurnal variation of withdrawal symptoms with severity being greatest at the daytime reading at 16.00 h and being markedly less at the night-time reading (recorded at 08.00 h). Lofexidine and clonidine were equally effective in treating the withdrawal syndrome. However, significantly more problems relating to hypotension were encountered with subjects on clonidine, with twice as many instances of withholding medication due to hypotension in the clonidine group. Better treatment retention rates were seen in the lofexidine group, although no difference was found in the proportion who had reached minimal symptom severity by the time of their discharge. We conclude that lofexidine and clonidine are equally effective, but with significantly fewer hypotensive problems with lofexidine. Further benefit from lofexidine may be possible with revised dosing regimens. Outpatient studies of lofexidine are now indicated.", "Our clinic has fortuitously developed the therapeutic use of the association of mianserin (maximum daily dose 90 mg) and carbamazepine (maximum daily dose 400 mg) in opiate withdrawal management. If animal studies have suggested efficacy of mianserin in such indication, no human studies have been performed. To test the efficacy of such an association, a comparison was made to clonidine (maximum daily dose 0.600 mg) in a one week treatment period according to a double blind pilot study design. Thirty-two patients were included (16 in each treatment group). The two treatments did not differ in the intensity of the withdrawal, according to the rate of retention in treatment and symptoms, and the psychic distress which were auto-evaluated every other day with the Opiate Withdrawal Questionnaire and several Visual Analog Scales (VAS). The clonidine group, however, scored significantly higher (P < 0.05) on the VAS rating of the global feeling of satisfaction on the last day. The patients in the mianserin group fortuitously had a moderately lower number of daily heroin intakes but there was no significant correlation between this variable and the global OWQ scores on Days 1, 3, 5 and 7. Given the size of the groups, we cannot conclude that the association carbamazepine-mianserin is as effective as clonidine, but a real effectiveness is probable. A study versus placebo would be necessary to draw more definitive conclusions.", "With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.", "Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine.\n To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo.\n An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11).\n Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo.\n Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day).\n Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01).\n Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.", "This study compares the clinical response to lofexidine and clonidine in the out-patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised double-blind study design. Patients were taking 40 mg or less methadone daily, or equivalent amounts of other opiates. Fifty-eight percent of those starting treatment completed detoxification, and were opiate free at 4 weeks: more patients completed withdrawal in the lofexidine group, but the difference was not significant. Clonidine produced more hypotensive effects: more home visits were also required by medical staff. There was no other significant difference in side effects. Both drugs can be used successfully in out-patient detoxification, but lofexidine is more economical in regard to staff time." ]